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Zheng HL, Zhang LK, Lv CB, Xu BB, Lin JX, Zheng CH, Huang CM, Xie JW. Impact of dynamic changes of tumor marker in neoadjuvant chemotherapy-treated triple-negative gastric cancer patients: a multi-center study. BMC Cancer 2024; 24:1188. [PMID: 39333952 PMCID: PMC11438086 DOI: 10.1186/s12885-024-12937-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Independent and valid prognostic predictors for locally advanced gastric cancer (LAGC) patients with non-elevated serum tumor markers (Triple-negative: CA199 < 37U/ml, CEA < 5 µg/ml and CA125 < 35U/ml) before and after neoadjuvant chemotherapy (NACT) remain unclear. METHODS A total of 352 LAGC patients treated with NACT(NLAGC) from two centers were included. Of the 156 were Triple-negative patients. CA72-4 trajectory groupings was defined as longitudinal changes in CA72-4 levels before and after NACT to identify different potential subgroups and to compare recurrence-free survival (RFS) and overall survival (OS) among subgroups. The predictive performance of the nomogram-trajectory was evaluated using the area under the receiver operating characteristic curve(AUC), decision curve analysis, and C-index. RESULTS In the Triple-negative patients, the Stable group had significantly worse 3-year OS than the Normal, Elevated, and Descend groups(3-year OS: 53.9% vs. 77.9% vs. 73.5% vs. 87.7%;P = 0.002). Cox multivariate analysis showed that CA72-4 trajectory groupings (Stable group: HR:3.442, 95%CI[1.574-7.528], P = 0.002) was an independent prognostic risk factor. In addition, the C-index and AUC values based on the nomogram-trajectory were significantly higher than those of ypTNM staging (C-index: 0.788 vs. 0.719,P < 0.001;AUC: 0.800 vs. 0.667,P < 0.001). Furthermore, The survival analysis revealed that the 3-year OS of the Low-Risk group of nomogram scores was significantly better than that of the High-Risk group(3-year OS:84.7% vs. 29.1%). And the Low-Risk group had the lower cumulative risk of recurrence (P < 0.001). CONCLUSION The CA72-4 trajectory groupings were an independent prognostic factor for NLAGC Triple-negative patients. The predictive efficacy of the Nomogram-trajectory was significantly better than the ypTNM.
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Affiliation(s)
- Hua-Long Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ling-Kang Zhang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chen-Bin Lv
- Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, China
| | - Bin-Bin Xu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China.
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, China.
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
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Liu C, Chen C, Peng F, Liang H, Zhong S, Liu T, Li L, Boronin A, Dong W. Determination of serum CA724 levels using fluorescence immunochromatography. BMC Biotechnol 2023; 23:30. [PMID: 37596558 PMCID: PMC10436430 DOI: 10.1186/s12896-023-00801-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 08/08/2023] [Indexed: 08/20/2023] Open
Abstract
BACKGROUND Carbohydrate antigen 724 (CA724) is a sensitive and specific indicator for multiple malignant tumors. The aim of this study was to establish a Eu-time resolved fluorescence immunochromatography (Eu-TRFICO) method for quantitative detection of CA724 in serum. METHODS Eu-TRFICO strips were optimized and assembled. The sensitivity, specificity and precision were evaluated using CA724 standard dilutions and matrix serum. Meanwhile, the reference interval, comparison, and sensitivity/specificity were performed using clinical negative/positive gastric cancer serum samples. RESULTS The standard curve equation was y = 9.869 x - 154.12 (R2 = 0.993), and the sensitivity was 0.42 U/mL. The common interferents in serum could not affect the quantitative results with low cross-reactivities (all no more than 1.09%). All average recoveries of the intra- and interbatch ranged from 102.38 to 106.40%, and all CVs were below 10%. The reference interval of the healthy subjects was < 4.68 U/mL and the reference interval of the subjects with grade I/II gastric cancer was > 9.54 U/mL. Additionally, a high Pearson r (0.9503) and sensitivity/specificity (92.86%/94.20%) were obtained. CONCLUSION This study prepared Eu-TRFICO strips with high sensitivity, specificity, precision and satisfactory clinical testing performance, which provides more options for clinical quantitative and convenient testing of CA724.
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Affiliation(s)
- Chang Liu
- Heilongjiang Academy of Chinese Medicine Sciences, Harbin, 150036, China
| | - Cuicui Chen
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, 510663, China
- Jinan Laide Bio-technology Co., Ltd, Jinan, 271100, China
| | - Fenglan Peng
- Taian Disabled Soldiers' Hospital of Shandong Province, Taian, 271000, China
| | - Huankun Liang
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, 510663, China
| | - Shuhai Zhong
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, 510663, China
| | - Tiancai Liu
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China
| | - Laiqing Li
- Guangzhou Youdi Bio-technology Co., Ltd, Guangzhou, 510663, China
| | - Alexander Boronin
- Laboratory of Plasmid Biology, G.K. Skryabin Institute Of Biochemistry and Physiology of Microorganisms Russian Academy of Sciences, Pushchino, 142290, Russia
| | - Wenqi Dong
- Guangzhou Zhenda Biopharmaceutical Technology Co., Ltd, No. 3 Juquan Road, Huangpu District, Guangzhou, 510663, China.
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Nguyen HT, Do KH, Le NB, Tran T. Treatment Outcome and Safety of the TCX Regimen for Advanced Gastric Cancer: A Prospective Cohort Study. Cancer Manag Res 2022; 14:2825-2837. [PMID: 36164467 PMCID: PMC9507975 DOI: 10.2147/cmar.s384325] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 09/12/2022] [Indexed: 11/23/2022] Open
Abstract
Objective To evaluate the outcome and safety of the paclitaxel, carboplatin, and capecitabine (TCX) regimen in patients with advanced gastric cancer. Methods Advanced gastric cancer patients received the TCX regimen for up to six cycles, which were 3 weeks apart. Paclitaxel (175 mg/m2) was given over a 3-hour infusion, followed by carboplatin in a 1-hour infusion on day 1. Capecitabine (850 mg/m2) was given orally twice daily from day 1 to day 14. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Results Among 83 patients at stage IVa and IVb, the median PFS was 9.3 months; 6-month, 1-year, and 2-year PFS were 74.6%, 32.5%, and 14.4%, respectively. The median OS was 17.0 months; 6-month, 1-year, and 2-year OS were 97.5%, 68.7%, and 21.7%, respectively. In the multivariable Cox regression model, higher CEA was associated with poor OS. Common adverse events included hand-food syndrome (77.9%), peripheral neuropathy (63.2%), fatigue (68.7%), and nausea (54.2%). Conclusion The TCX regimen provided good survival and a better safety profile. More clinical trials are needed to confirm its treatment efficacy and safety, especially in comparison with other triplet regimens.
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Affiliation(s)
- Hieu Trong Nguyen
- Department of Medical Oncology 2, Hanoi Oncology Hospital, Hanoi, Vietnam
| | - Kien Hung Do
- Department of Medical Oncology 1, National Cancer Hospital of Vietnam, Hanoi, Vietnam
| | | | - Thang Tran
- Department of Medical Oncology 4, National Cancer Hospital of Vietnam, Hanoi, Vietnam
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Liu C, Chen C, Lai H, Liang H, Zhong S, Guo G, Wang L, Li L. A New Method for Early Screening of Gastric Cancer (G17 and CA724 Dual-Labeled Time-Resolved Fluorescence Immunoassay). COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:1704948. [PMID: 35912162 PMCID: PMC9328981 DOI: 10.1155/2022/1704948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/30/2022] [Accepted: 07/05/2022] [Indexed: 11/18/2022]
Abstract
Gastric carcinoma (GC) is one of the most common malignancies in the world with the great early screening challenges. The study is aimed at establishing a new detection method for early screening GC using time-resolved fluorescence immunoassay (TRFIA) via quantitative detection of gastrin-17 (G-17) and carbohydrate antigen 724 (CA724) in serum. Time-resolved analyzer measured the fluorescence intensity. The standards of G-17/CA724 were used for drawing the standard curve, which is used to calculate the concentration of G-17 and CA724 in serum sample. The sensitivity for G-17 was 0.54 pg/mL and for CA724 was 0.28 U/mL with a wide-range analyze concentration (0.1-1000) pg/mL or U/mL. The average recoveries ranged from 100.52% to 110.30% for G-17 and 103.02% to 116.00% for CA724. All CVs of the intra- and interassay were below 10% with high specificity. There was a high Pearson coefficient between this TRFIA method and the commercially available kits (Pearson r 0.9117 for G-17 and 0.9449 for CA724). Additionally, the cutoff value was 88.41 pg/mL and 5.47 U/mL for CA724 in health subjects. This study established a TRFIA method for simultaneous detection of the concentrations of G-17 and CA724 in serum, which provide a new method for sensitive, accurate, and specific early screening of gastric cancer.
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Affiliation(s)
- Chang Liu
- Heilongjiang Academy of Chinese Medicine Sciences, Harbin, 150036, China
| | - Cuicui Chen
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Hongrui Lai
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Huankun Liang
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Shuhai Zhong
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Guiling Guo
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Lei Wang
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
| | - Laiqing Li
- Guangzhou Youdi Bio-Technology Co., Ltd., Guangzhou 510663, China
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Ma Z, Zhu T, Wang H, Wang B, Fu L, Yu G. Investigation of serum markers of esophageal squamous cell carcinoma based on machine learning methods. J Biochem 2022; 172:29-36. [PMID: 35415740 DOI: 10.1093/jb/mvac030] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 03/19/2022] [Indexed: 11/15/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the malignant tumors with high mortality in humans, and there is a lack of effective and convenient early diagnosis methods. By analyzing the serum miRNA expression data in ESCC tumor samples and normal samples, on the basis of the max-relevance and min-redundancy (mRMR) feature selection and the incremental feature selection (IFS) method, a random forest classifier constructed by 5 feature miRNAs was acquired in our study. The receiver operator characteristic (ROC) curve showed that the model was able to distinguish samples. Principal component analysis (PCA) and sample hierarchical cluster analysis showed that 5 feature miRNAs could well distinguish ESCC patients from healthy individuals. The expression levels of miR-663a, miR-5100 and miR-221-3p all showed a higher expression level in ESCC patients than those in healthy individuals. On the contrary, miR-6763-5p and miR-7111-5p both showed lower expression levels in ESCC patients than those in healthy individuals. In addition, the collected clinical serum samples were used for qRT-PCR analysis. It was uncovered that the expression trends of the 5 feature miRNAs followed a similar pattern with those in the training set. The above findings indicated that the 5 feature miRNAs may be serum tumor markers of ESCC. This study offers new insights for the early diagnosis of ESCC.
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Affiliation(s)
- Zhifeng Ma
- Department of Thoracic Surgery, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China, 312000
| | - Ting Zhu
- Department of Thoracic Surgery, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China, 312000
| | - Haiyong Wang
- Department of Thoracic Surgery, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China, 312000
| | - Bin Wang
- Department of Thoracic Surgery, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China, 312000
| | - Linhai Fu
- Department of Thoracic Surgery, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China, 312000
| | - Guangmao Yu
- Department of Thoracic Surgery, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, China, 312000
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Kim JH, Suh YJ, Park D, Yim H, Kim H, Kim HJ, Yoon DS, Hwang KS. Technological advances in electrochemical biosensors for the detection of disease biomarkers. Biomed Eng Lett 2021; 11:309-334. [PMID: 34466275 PMCID: PMC8396145 DOI: 10.1007/s13534-021-00204-w] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 08/13/2021] [Accepted: 08/20/2021] [Indexed: 12/15/2022] Open
Abstract
With an increasing focus on health in contemporary society, interest in the diagnosis, treatment, and prevention of diseases has grown rapidly. Accordingly, the demand for biosensors for the early diagnosis of disease is increasing. However, the measurement range of existing electrochemical sensors is relatively high, which is not suitable for early disease diagnosis, requiring the detection of small amounts of biocomponents. Various attempts have been made to overcome this and amplify the signal, including binding with various labeling molecules, such as DNA, enzymes, nanoparticles, and carbon materials. Efforts are also being made to increase the sensitivity of electrochemical sensors, and the combination of nanomaterials, materials, and biotechnology offers the potential to increase sensitivity in a variety of ways. Recent studies suggest that electrochemical sensors can be a powerful tool in providing comprehensive insights into the targeting and detection of disease-associated biomarkers. Significant advances in nanomaterial and biomolecule approaches for improved sensitivity have resulted in the development of electrochemical biosensors capable of detecting multiple biomarkers in real time in clinically relevant samples. In this review, we have discussed the recent studies on electrochemical sensors for detection of diseases such as diabetes, degenerative diseases, and cancer. Further, we have highlighted new technologies to improve sensitivity using various materials, including DNA, enzymes, nanoparticles, and carbon materials.
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Affiliation(s)
- Jae Hyun Kim
- Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447 Republic of Korea
| | - Young Joon Suh
- Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447 Republic of Korea
| | - Dongsung Park
- Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447 Republic of Korea
- School of Biomedical Engineering, Korea University, Seoul, 02841 Republic of Korea
| | - Hyoju Yim
- Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447 Republic of Korea
| | - Hongrae Kim
- Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447 Republic of Korea
- School of Biomedical Engineering, Korea University, Seoul, 02841 Republic of Korea
| | - Hye Jin Kim
- Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447 Republic of Korea
| | - Dae Sung Yoon
- School of Biomedical Engineering, Korea University, Seoul, 02841 Republic of Korea
| | - Kyo Seon Hwang
- Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Kyungheedae-ro 26, Dongdaemun-gu, Seoul, 02447 Republic of Korea
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Xu Y, Zhang P, Zhang K, Huang C. The application of CA72-4 in the diagnosis, prognosis, and treatment of gastric cancer. Biochim Biophys Acta Rev Cancer 2021; 1876:188634. [PMID: 34656687 DOI: 10.1016/j.bbcan.2021.188634] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 10/09/2021] [Accepted: 10/10/2021] [Indexed: 02/07/2023]
Abstract
The role of conventional serum tumor marker, carbohydrate antigen 72-4 (CA72-4), in assisting diagnosis, monitoring dynamic progression, and evaluating the prognosis of gastric cancer (GC) should not be ignored, especially in the Chinese population. Even though CA72-4 has been used in clinical practice for decades, its modest positivity rate, sensitivity, and specificity did not meet the high demand of the clinical application. However, over the years, some progress in the functions of CA72-4 has been achieved, suggesting that CA72-4 can still be considered a promising marker in oncology. As a biomarker, CA72-4 can achieve improved sensitivity (SEN) and specificity (SPE) when combined with other biomarkers, selecting suitable reference values, improving detection techniques, and identifying the risk threshold. As a predictor, elevated serum CA72-4 levels were found to be significantly associated with prognostic risk factors, further assessing therapeutic validity and resectability. Recently, an effective method to reduce the toxicity of CA72-4 targeted therapy has been developed. Moreover, CA72-4 could induce novel aptamers to react with tumor cells and enhance the efficacy of trastuzumab in HER2-positive GC. Therefore, in this review, we discuss the most recent application of CA72-4 in the diagnosis, prognosis, and treatment of GC.
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Affiliation(s)
- Yitian Xu
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China
| | - Pengshan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China
| | - Kundong Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China
| | - Chen Huang
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China.
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Zhang Z, Peng M, Li D, Yao J, Li Y, Wu B, Wang L, Xu Z. Carbon Material Based Electrochemical Immunosensor for Gastric Cancer Markers Detection. Front Chem 2021; 9:736271. [PMID: 34532312 PMCID: PMC8438142 DOI: 10.3389/fchem.2021.736271] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 08/16/2021] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer is one of the most common malignant tumors, and early diagnosis will be of great significance to improve the survival quality and overall treatment outcome evaluation of patients. Nanoelectrochemical immunosensor is an emerging biosensor combining nanotechnology, electrochemical analysis method and immunological technology, which has simple operation, fast analysis speed, high sensitivity, and good selectivity. This mini-review summarized immunoassay techniques, nanotechnology and electrochemical sensing for the early detection of gastric cancer. In particular, we focus on the tension of carbon nanomaterials in this field, including the functionalized preparation of materials, signal enhancement and the construction of novel sensing interfaces. Currently, various tumor markers are being developed, but the more recognized gastric cancer tumor markers are carcinoembryonic antigen (CEA), carbohydrate antigen (CA), CD44V9, miRNAs, and programmed death ligand 1. Among them, the electrochemical immunosensor allows the detection of CEA, CA, and miRNAs. The mini-review focused on the development of using carbon based materials, especially carbon nanotubes and graphene for immunosensor fabrication and gastric cancer markers detection.
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Affiliation(s)
- Zhuliang Zhang
- Department of Gastroenterology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China
| | - Minsi Peng
- Department of Gastroenterology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China
| | - Defeng Li
- Department of Gastroenterology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China
| | - Yingxue Li
- Department of Gastroenterology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China
| | - Benhua Wu
- Department of Gastroenterology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China
| | - Lisheng Wang
- Department of Gastroenterology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China
| | - Zhenglei Xu
- Department of Gastroenterology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, China
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Jin YY, Yang WZ, Sun ZY, Wang ZB, Chen J, Wu CT, Yang ZY. NK cells adjuvant therapy shows survival benefits in a gastric mixed signet ring cell carcinoma patient: A case report. Medicine (Baltimore) 2021; 100:e24979. [PMID: 33725867 PMCID: PMC7969222 DOI: 10.1097/md.0000000000024979] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 02/11/2021] [Indexed: 01/05/2023] Open
Abstract
RATIONALE Advanced signet ring cell (SRC) carcinoma has a worse prognosis. Therefore, early diagnosis and prevention is particularly important; SRC tumors have lower R0 resection rate and are thought to be less chemosensitive than non-SRCC. Consequently, a novel postoperative adjuvant treatment is urgently needed to improve clinical outcomes. PATIENT CONCERNS A 41-year-old female with advanced gastric SRC carcinoma was treated with radical gastrectomy and oxaliplatin-based regimen for 6 cycles after surgery. She was suspected of recurrence with the high level of carbohydrate antigen (CA) 72-4. DIAGNOSES The gastroscopy revealed SRC carcinoma of gastric antrum and poorly differentiated adenocarcinoma in some areas. The diagnosis of postoperative pathology report was gastric cancer with stage III C (T4a, N3a, M0). INTERVENTIONS The level of CA72-4 rapidly increased during the 2 follow-up after the completion of conventional treatment, ex vivo-cultured allogeneic natural killer (NK) cell infusion was offered to prevent recurrence. OUTCOMES Intravenous injections of NK cells combination with surgical treatment and chemotherapy showed therapeutic effects in this patient with possible relapse. The patient remained disease-free 46 months after the infusion of NK cells until the latest follow-up. LESSONS CA72-4 appeared to be the most sensitive and specific marker in the gastric cancer patient, and the high level of CA72-4 may indicate the risk of recurrence. This case report provide rationale for NK cell infusion following the rapid increase of CA72-4 to prevent recurrence.
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MESH Headings
- Adult
- Antigens, Tumor-Associated, Carbohydrate/blood
- Antigens, Tumor-Associated, Carbohydrate/immunology
- Carcinoma, Signet Ring Cell/diagnosis
- Carcinoma, Signet Ring Cell/immunology
- Carcinoma, Signet Ring Cell/pathology
- Carcinoma, Signet Ring Cell/therapy
- Combined Modality Therapy/methods
- Female
- Gastrectomy
- Humans
- Killer Cells, Natural/transplantation
- Neoplasm Staging
- Postoperative Care/methods
- Prognosis
- Stomach Neoplasms/diagnosis
- Stomach Neoplasms/immunology
- Stomach Neoplasms/pathology
- Stomach Neoplasms/therapy
- Transplantation, Homologous
- Treatment Outcome
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Affiliation(s)
- Yuan-Yuan Jin
- NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing
| | - Wen-Zhuo Yang
- Sun Yat-sen University School of Medicine, Guangzhou
| | - Zheng-Yang Sun
- NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing
| | - Zhong-Bo Wang
- NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing
| | - Jian Chen
- Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong
| | - Chun-Tao Wu
- North China University of Science and Technology Affiliated Hospital, Tangshan, China
| | - Zhao-Yong Yang
- NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing
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Zhang M, Wang X, Wang Z. Early Study of Tumor Abnormal Protein in Gastric Adenocarcinoma. Onco Targets Ther 2021; 14:1719-1726. [PMID: 33707954 PMCID: PMC7943549 DOI: 10.2147/ott.s297413] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 02/13/2021] [Indexed: 12/25/2022] Open
Abstract
Objective To study the correlation between tumor abnormal protein (TAP) and tumor markers, blood glucose, uric acid and coagulation function in gastric adenocarcinoma and to evaluate the clinical application of TAP in the diagnosis of gastric adenocarcinoma. Methods A total of 34 nontumor patients and 95 gastric adenocarcinoma patients admitted to the First Affiliated Hospital of Jinzhou Medical University were enrolled in this study. Fresh blood from patients' fingertips was collected, all blood samples were examined with TAP testing kit, and then searched and measured the condensed particulate matter. Results The comparison of TAP between nontumor patients and gastric adenocarcinoma patients was statistically significant (P<0.05). Bivariate correlation analysis was conducted between TAP and other related tumor markers (alpha-fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9 (CA199), carbohydrate antigen 72-4 (CA72-4)), blood glucose, uric acid, and coagulation function-related indicators, and the results showed that the correlation between TAP and CA199, CA72-4, and activated partial prothrombin time was statistically significant. In addition, according to the analysis results, there was no significant difference among TAP and age, height and weight in the tumor population and the nontumor population. Conclusion TAP can be used for the screening and diagnosis of gastric adenocarcinoma, and the effect of TAP combined with other indicators is more significant than TAP alone.
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Affiliation(s)
- Ming Zhang
- Department of Gastrointestinal Oncology (Ward I), The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People's Republic of China
| | - Xiaoyu Wang
- Department of Gastrointestinal Oncology (Ward I), The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People's Republic of China
| | - Zhenghua Wang
- Department of Gastrointestinal Oncology (Ward I), The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People's Republic of China
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11
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Cai Q, Zhou W, Li J, Ou X, Chen C, Cai S, He W, Xu J, He Y. Association of Preoperative Serum Carcinoembryonic Antigen and Gastric Cancer Recurrence: A Large Cohort Study. J Cancer 2021; 12:397-403. [PMID: 33391436 PMCID: PMC7738990 DOI: 10.7150/jca.47899] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 10/25/2020] [Indexed: 02/06/2023] Open
Abstract
Background and Aim: Measuring postoperative carcinoembryonic antigen (CEA) is recommended by guidelines to help detecting recurrence of gastric cancer patients. However, the prognostic significance of elevated preoperative CEA is unclear. This study aims to investigate whether patients with elevated preoperative CEA have a higher risk of recurrence than patients with normal preoperative CEA. Methods: We conducted a retrospective cohort study at a gastric cancer center in South China. Consecutive patients with stage I to III gastric adenocarcinoma who underwent curative resection at the center from January 2001 to February 2016 were identified. Patients were grouped into two cohorts: normal preoperative CEA (≤ 5 ng/ml), and elevated preoperative CEA (> 5 ng/ml). 3-year recurrence-free survival (RFS) and hazard function curves over time were estimated. Results: A total of 1,596 patients (1,063 {66.6%} male; median {Interquartile range, IQR} age, 59 {50-66} years) were identified. Patients with elevated preoperative CEA had 15.5% lower 3-year RFS (n=222 {70.4%}) than the cohorts with normal preoperative CEA (n=1,374 {85.9%}). The hazard function of recurrence for the two cohorts peaked at the similar time (around 10 months after surgery). Multivariate Cox analyses confirmed that elevated preoperative CEA was independently associated with shorter RFS (Hazard Ratio {HR}, 1.69; 95% confidence interval {CI}, 1.26-2.27; P = 0.001). Conclusions: Patients with elevated preoperative CEA are at increased risk for recurrence, especially within the first 24 months after surgery.
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Affiliation(s)
- Qinbo Cai
- Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.,Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangzhou, P. R. China.,Laboratory of General Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China
| | - Wen Zhou
- Laboratory of General Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China
| | - Jin Li
- Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.,Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangzhou, P. R. China.,Laboratory of General Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.,Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, P. R. China
| | - Xinde Ou
- Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.,Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangzhou, P. R. China.,Laboratory of General Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China
| | - Chuangqi Chen
- Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.,Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangzhou, P. R. China
| | - Shirong Cai
- Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.,Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangzhou, P. R. China
| | - Weiling He
- Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.,Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangzhou, P. R. China
| | - Jianbo Xu
- Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.,Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangzhou, P. R. China
| | - Yulong He
- Center of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.,Center for Diagnosis and Treatment of Gastric Cancer, Sun Yat-sen University, Guangzhou, P. R. China.,Center for Digestive Disease, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, P. R. China
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12
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Clinical Evaluation of Serum Tumor Markers in the Diagnosis of Gastric Adenocarcinoma Staging and Grading. J Gastrointest Cancer 2020; 50:525-529. [PMID: 29806060 DOI: 10.1007/s12029-018-0091-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
ᅟ: Detection and quantitative measurements of diffused tumor markers in blood samples of patients with cancer is a facile and convenient method to determine prognosis and the appropriateness of the treatment. This study was done to evaluate the level of CA125, CEA, AFP, Beta HCG, and CA19-9 tumor markers and their relation to the stage and grade of the disease in patients with gastric adenocarcinoma. MATERIALS AND METHODS In a descriptive cross-sectional study, of 81 patients referred to the oncology department of Tohid Hospital, Sanandaj, Iran, in 1 year, with recently detected gastric adenocarcinoma, serum level of CEA, CA19-9, CA125, AFP, and Beta HCG tumor markers was measured by ELISA method before chemotherapy and surgery. Patients were divided into four groups based on stage of disease (I, II, III, IV), and in terms of tumor differentiation, degrees were classified in to three groups: low, high, and intermediate. To determine the correlation of tumor markers level with the stage and grade of the disease, the Kruskal-Wallis and Mann-Whitney U tests were used. RESULTS By progression, the stages of the disease, the serum level of CA19-9, CA125, and AFP tumor markers demonstrated a significant increase. But this difference between level of HCG and CEA was not significant with the staging. There was no significant difference between the serum level of tumor markers and the grading of disease in the patients. CONCLUSION Preoperative CA19-9, CA125, and AFP tumor markers measurements could be beneficial in detecting the progressed stages of the disease.
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13
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Sun Z, Jia J, Du F, Yang Y, Liu C, Xiao Y, Yu J, Zhang X. Clinical significance of serum tumor markers for advanced gastric cancer with the first-line chemotherapy. Transl Cancer Res 2019; 8:2680-2690. [PMID: 35117026 PMCID: PMC8799103 DOI: 10.21037/tcr.2019.10.27] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Accepted: 10/10/2019] [Indexed: 12/27/2022]
Abstract
Background Tumor markers play an important role in the diagnosis, monitoring and prognostic prediction of cancers. But the predictive value of serum tumor markers in gastric cancer is still unclear. Methods In this study, we detected serum levels of tumor markers to evaluate their relation to treatment response and prognosis in patients with unresectable advanced or metastatic gastric cancer. Results We collected the clinical data of 109 patients with unresectable advanced or metastatic gastric cancer who had received the first-line chemotherapy in Peking University Cancer Hospital from July 2013 to May 2015, and collected the value of serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 72.4 (CA72.4) and carbohydrate antigen 125 (CA125) before and after chemotherapy. At diagnosis, the positive rates of CEA, CA199, CA72.4 and CA125 were 46.8%, 40.2%, 53.5% and 35.0%, respectively. And the positive rate of combined detection of the four markers was 87.2%. Although patients with prechemotherapy CA199 ≥80 U/mL (92.3% vs. 68.5%, P=0.016) or CA72.4 ≥20 U/mL (91.4% vs. 62.5%, P=0.003) had higher clinical benefit rate after chemotherapy, they showed poorer prognosis (P=0.023 and P=0.006, respectively). CA72.4 ≥20 U/mL was an independent unfavorable prognostic factor (Hazard Ratio 4.84; 95% confidence interval: 1.910–12.262; P=0.001). In patients with increased levels of tumor markers before treatment, the levels of tumor markers decreased after chemotherapy, especially in those with clinical benefit (CEA, CA72.4 reached statistical significance, P=0.013 and P=0.029, respectively). A decrease of CEA ≥35%, CA199 ≥30%, or CA72.4 ≥40% after chemotherapy had positive prediction value for the response to chemotherapy (P=0.016, P=0.029, and P=0.008, respectively). Conclusions The results showed that both high pre-chemotherapy serum levels of tumor markers (CA199 ≥80 U/mL or CA72.4 ≥20 U/mL) and a substantial decrease in tumor markers after chemotherapy (CEA ≥35%, CA199 ≥30%, or CA72.4 ≥40%) could predict a higher clinical benefit rate in patients with unresectable advanced or metastatic gastric cancer. However, this advantage in short-term response to chemotherapy failed to convert into prolonged survival benefits.
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Affiliation(s)
- Zhiwei Sun
- VIP-II Division of Medical Department, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Jun Jia
- VIP-II Division of Medical Department, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Feng Du
- VIP-II Division of Medical Department, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ying Yang
- VIP-II Division of Medical Department, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Chuanling Liu
- VIP-II Division of Medical Department, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Yanjie Xiao
- VIP-II Division of Medical Department, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Jing Yu
- VIP-II Division of Medical Department, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xiaodong Zhang
- VIP-II Division of Medical Department, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
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14
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Yoon JH, Park YG, Nam SW, Park WS. The diagnostic value of serum gastrokine 1 (GKN1) protein in gastric cancer. Cancer Med 2019; 8:5507-5514. [PMID: 31376239 PMCID: PMC6745860 DOI: 10.1002/cam4.2457] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 07/16/2019] [Accepted: 07/16/2019] [Indexed: 12/16/2022] Open
Abstract
Early detection of cancer provides effective treatment and saves lives. The objective of this study was to determine whether serum gastrokine 1 (GKN1) protein is a gastric cancer‐specific diagnostic biomarker. The serum concentration of GKN1 in healthy individuals (median: 6.34 ng/μL, interquartile range (IQR): 5.66‐7.54 ng/μL) was significantly higher compared with the levels in gastric cancer patients (median: 3.48 ng/μL, IQR: 2.90‐4.11 ng/μL; P < .0001). At the optimum cutoff (4.94 ng/μL) of serum GKN1 protein, the sensitivity and specificity were 91.2% and 96.0%, respectively, for gastric cancer. Using serum GKN1 protein as the diagnostic reference, the ROC curve showed a satisfactory diagnostic efficacy with an AUC value of 0.9954 (95% CI 0.9919‐0.9988) and Youden index of 0.8740. In addition, the diagnostic accuracy of the serum GKN1 protein at the optimum cutoff was 0.9675. Interestingly, serum GKN1 concentrations in patients with advanced gastric cancer (AGC; median: 3.11 ng/μL, IQR: 2.72‐3.72 ng/μL) were lower than in patients with early gastric cancer (EGC; median: 4.31 ng/μL, IQR: 3.88‐4.88 ng/μL). The diagnostic accuracies at the optimum serum GKN1 cutoff were 0.8912 and 0.9589 for EGC and AGC, respectively. Furthermore, the serum GKN1 concentrations robustly discriminated the patients with gastric cancer from the patients with colorectal, liver, lung, breast, pancreatic, ovary, and prostatic cancers with AUC values greater than 0.94. These data suggest that serum GKN1 is a promising and highly specific diagnostic biomarker for the prompt detection of early and advanced gastric cancers.
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Affiliation(s)
- Jung Hwan Yoon
- Department of Pathology, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
- Functional RNomics Research Center, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
| | - Yong Gyu Park
- Department of Biostatistics, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
| | - Suk Woo Nam
- Department of Pathology, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
- Functional RNomics Research Center, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
| | - Won Sang Park
- Department of Pathology, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
- Functional RNomics Research Center, College of MedicineThe Catholic University of KoreaSeoulSouth Korea
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15
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Li QH, Yu M, Ding YL, Chen YX. ANKRD33 is overexpressed in gastric adenocarcinoma and predictive for poor prognosis. Biosci Biotechnol Biochem 2019; 83:2075-2081. [PMID: 31314707 DOI: 10.1080/09168451.2019.1642100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
The aim of the current study was to investigate and discuss the function of ANKRD33 gene in the pathogenesis of gastric adenocarcinoma. The marked up-regulated expression of ANKRD33 gene in gastric adenocarcinoma tissues compared to normal tissues was found by bioinformatics analysis. Kaplan-Meier analysis revealed that high expression of ANKRD33 is correlated with lower overall survival of gastric adenocarcinoma patients. The results of qPCR revealed that mRNA expression level of ANKRD33 was dramatically higher in AGS, SGC7901, and BGC823 cell lines than that in the GES1 cells. Knockdown of ANKRD33 remarkably inhibited the viability, invasion, and migration of AGS and BGC823 cells. Furthermore, the ratio of p-AKT/AKT and p-mTOR/mTOR was significantly decreased in AGS cells which transfected with si- ANKRD33. All the above results illustrated that ANKRD33 would act as a tumor forwarder in gastric adenocarcinoma development and have a high potential to be a marker molecule in the diagnosis and treatment of gastric tumors.
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Affiliation(s)
- Quan-Hui Li
- Department of Gastrointestinal Surgery, The Second Hospital of ShanDong University , Jinan , P.R. China
| | - Miao Yu
- Department of Colorectal & Anal Surgery, The Second Hospital of ShanDong University , Jinan , P.R. China
| | - Yin-Lu Ding
- Department of Gastrointestinal Surgery, The Second Hospital of ShanDong University , Jinan , P.R. China
| | - Yu-Xin Chen
- Department of General Surgery, Qilu Hospital Affiliated to ShanDong University , Jinan , Shandong , P.R. China
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16
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Jing J, Ge M, Yang Z, Li P. Spatial distribution characteristics of tumor marker CA724 reference values in China. Cancer Med 2019; 8:4465-4474. [PMID: 31199587 PMCID: PMC6675733 DOI: 10.1002/cam4.2176] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Revised: 04/01/2019] [Accepted: 04/03/2019] [Indexed: 12/16/2022] Open
Abstract
Objects This study aims to explore the Cancer antigen 724 (CA724) reference values spatial distribution characteristics in healthy Chinese adults. The study can provide regional reference for medical diagnosis. Study Design The relationship between CA724 and 25 geographical environmental factors was analyzed firstly. Artificial neural network simulation training was used to construct the prediction model. The national forecast distribution map of the CA724 reference values was obtained by the geostatistical mapping method. Analyzing and exploring the influence mechanism of geographical environment factors on CA724 reference values. Methods Collecting 34470 cases from more than 106 cities healthy adults CA724 reference values via several paper databases in 10 recent years. Correlation analysis, RBF artificial neural networks and trend surface analysis were applied to explore if there was any tendency of spatial variation. The Kriging interpolation of geostatistical analysis was developed to reveal the spatial distribution characteristics of the CA724 reference values. Results The distribution of CA724 reference values of Chinese healthy adults shows a downward trend from south to north. CA724 reference values have negative correlations with latitude, annual sunshine duration and topsoil cation exchange capacity in clay. CA724 have positive correlations with annual mean air temperature, annual mean relative humidity, and annual precipitation amount. High temperature and high humidity environment will reduce gastrointestinal function and breeze various mold bacteria. Lack of sunshine can easily lead to vitamin C deficiency in the body. These will increase the incidence of gastrointestinal diseases and gastric cancer, then increase the CA724 value. Conclusion CA724 reference values show spatial autocorrelation and regional variation. There are some geographical environment factors effected Chinese healthy adults CA724 reference values. Geographic factors such as sunshine, temperature, and humidity have effects on CA724 reference values can provide new ideas and directions of prevention and clinical diagnosis in the future.
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Affiliation(s)
- Jing Jing
- Institute of Healthy Geography, College of Geography and Tourism, Shaanxi Normal University, Xi'an, Shaanxi, China.,Baoji University of Arts and Sciences, Baoji, Shaanxi, China
| | - Miao Ge
- Institute of Healthy Geography, College of Geography and Tourism, Shaanxi Normal University, Xi'an, Shaanxi, China
| | - Ziqi Yang
- Baoji University of Arts and Sciences, Baoji, Shaanxi, China
| | - Peng Li
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong Unversity Health Science Center, Xi'an, Shaanxi, China
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17
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Hu PJ, Chen MY, Wu MS, Lin YC, Shih PH, Lai CH, Lin HJ. Clinical Evaluation of CA72-4 for Screening Gastric Cancer in A Healthy Population: A Multicenter Retrospective Study. Cancers (Basel) 2019; 11:cancers11050733. [PMID: 31137895 PMCID: PMC6562516 DOI: 10.3390/cancers11050733] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 05/20/2019] [Accepted: 05/22/2019] [Indexed: 12/11/2022] Open
Abstract
Early detection is important for improving the survival rate of patients with gastric cancer (GC). Serum tumor markers have been widely used for detecting GC. However, their clinical values remain controversial. This study aims to investigate the role of serum cancer antigen 72-4 (CA72-4) in the diagnosis of GC in a healthy population. A total of 7757 adults who underwent upper gastrointestinal endoscopy and serum CA72-4 level measurement in multicenters in Taiwan from January 2006 to August 2016 were recruited in this retrospective study. Risk factors for GC, serum tumor markers, and esophagogastroduodenoscopy (EGD) findings were evaluated. High serum levels of CA72-4 were found in 7.2% of healthy adults. CA72-4 level showed lower sensitivity (33.3%) but higher specificity (92.8%); however, the positive predictive value was quite low (0.18%). After adjustment of clinical risk factors for GC using EGD findings, gastric ulcer (adjusted odds ratio (aOR) = 2.11), gastric polyps (aOR = 1.42), and atrophic gastritis (aOR = 1.27) were significantly associated with high serum CA72-4 levels. Furthermore, both age (OR = 1.01) and Helicobacter pylori infection (OR = 1.44) exhibited a significant association with high serum CA72-4 levels. These results indicate that routine screening of CA72-4 levels for diagnosing GC in asymptomatic patients may be ineffective due to low sensitivity and low positive predictive value. The clinical utility of EGD findings along with serum CA72-4 level for screening healthy individuals with GC is warranted.
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Affiliation(s)
- Ping-Jen Hu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackey Memorial Hospital, Taitung 95054, Taiwan.
| | - Ming-Yao Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang-Ho Hospital, New Taipei 23562, Taiwan.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Ming-Shun Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
- Division of Gastroenterology, Department of Internal Medicine, Wan-Fang Hospital, 11696 Taipei, Taiwan.
| | - Ying-Chin Lin
- Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
| | - Ping-Hsiao Shih
- Center for Cell Therapy, Department of Medical Research, School of Medicine, China Medical University and Hospital, Taichung 40447, Taiwan.
| | - Chih-Ho Lai
- Center for Cell Therapy, Department of Medical Research, School of Medicine, China Medical University and Hospital, Taichung 40447, Taiwan.
- Department of Microbiology and Immunology, Molecular Infectious Disease Research Center, Chang Gung University and Chang Gung Memorial Hospital, Linkou 33305, Taiwan.
| | - Hwai-Jeng Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang-Ho Hospital, New Taipei 23562, Taiwan.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
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18
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Bao J, Nanding A, Song H, Xu R, Qu G, Xue Y. The overexpression of MDM4: an effective and novel predictor of gastric adenocarcinoma lymph node metastasis. Oncotarget 2018; 7:67212-67222. [PMID: 27626496 PMCID: PMC5341869 DOI: 10.18632/oncotarget.11971] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 09/02/2016] [Indexed: 01/19/2023] Open
Abstract
Background MDM4 is the important negative regulator of the tumor suppressor protein p53, which is overexpressed in various human cancers. This study evaluates the MDM4 expression in patients with gastric adenocarcinoma (GTAC) at the mRNA and protein levels and examines relationships among MDM4 expression, clinicopathological features, and prognosis. Results The qRT-PCR and the Western blot analysis showed that the MDM4 expression level was high in GTACN+ but not in GTACN−. The high expression level of MDM4 was significantly associated with age (P = 0.047), lymph node metastasis (LNM) (P < 0.001), pathological stage (P < 0.001), differentiation status (P = 0.001), and preoperative serum CA19-9 level (P < 0.001). Moreover, the survival analysis showed that Borrmann type, depth of invasion, LNM, and preoperative serum CA19-9 level were independent prognostic factors. The univariate analysis revealed that MDM4 expression influenced GTAC prognosis. Furthermore, the influence of overall prognosis relies on whether or not the high MDM4 expression level could lead to LNM. Materials and Methods We investigated MDM4 expression in primary GTAC and paired normal gastric tissues (30 pairs) through qRT-PCR and Western blot analyses. We also performed immunohistochemistry analysis on 336 paraffin-embedded GTAC specimens and 33 matched normal specimens. Conclusions MDM4 expression may result in LMN of GTAC. High MDM4 expression levels are associated with LMN of GTAC and influence the prognosis of patients with GTAC.
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Affiliation(s)
- Junjie Bao
- Department of Gastroenterologic Surgery, Harbin Medical University Cancer Hospital, Harbin, China.,Department of Orthopedics, Harbin Medical University Cancer Hospital, Harbin, China
| | - Abiyasi Nanding
- Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Haibin Song
- Department of Gastroenterologic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Rui Xu
- Department of Dermatology, Harbin Children's Hospital, Harbin, China
| | - Guofan Qu
- Department of Orthopedics, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yingwei Xue
- Department of Gastroenterologic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
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19
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Aloe S, D'Alessandro R, Spila A, Ferroni P, Basili S, Palmirotta R, Carlini M, Graziano F, Mancini R, Mariotti S, Cosimelli M, Roselli M, Guadagni F. Prognostic value of Serum and Tumor Tissue CA 72-4 Content in Gastric Cancer. Int J Biol Markers 2018; 18:21-7. [PMID: 12699059 DOI: 10.1177/172460080301800104] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
To date no general agreement has been reached regarding the prognostic significance of CEA, CA 19-9 and CA 72-4 as serum markers in gastric cancer, and only scattered information is available on the predictive value of marker expression in tumor tissue. Therefore, a longitudinal study was designed to analyze the presurgical serum and tumor tissue content of CA 72-4, CEA and CA 19-9 in 166 patients at different stages of gastric cancer, and to evaluate the possible correlation with clinicopathological features in respect to prognostic information on relapse-free survival. The results obtained showed that 48.4% of patients with tumor recurrence had positive presurgical CA 72-4 levels compared to approximately 24% of patients who remained free of disease. Furthermore, the median presurgical serum CA 72-4 levels were significantly elevated in relapsing patients. Serosa and lymph node involvement as well as positive presurgical serum CA 72-4 levels had independent prognostic value in predicting recurrence. A significant association between disease-free survival and lymph node involvement, depth of invasion and tumor tissue content of CA 72-4 was also demonstrated. We may therefore conclude that CA 72-4 antigen can be considered the marker of choice in the follow-up of gastric cancer patients and may be used as a prognostic indicator of relapse.
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Affiliation(s)
- S Aloe
- Laboratory of Clinical Pathology, Regina Elena Cancer Institute, Rome, Italy
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20
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Combined preoperative concentrations of CEA, CA 19-9, and 72-4 for predicting outcomes in patients with gastric cancer after curative resection. Oncotarget 2018; 7:35446-53. [PMID: 27147574 PMCID: PMC5085242 DOI: 10.18632/oncotarget.9060] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2015] [Accepted: 04/11/2016] [Indexed: 12/14/2022] Open
Abstract
In many cancers, prognostic factors are useful for identifying high-risk patients and in individualizing treatment. We sought to determine whether a combination of tumor markers (CTM) would improve prognostic accuracy in patients with gastric cancer (GC). The CTM score, which is derived from serum concentrations of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and carbohydrate antigen 72-4 (CA 72-4), was tested retrospectively in 1134 patients with GC undergoing curative resection between October 2000 and December 2012. The CTM score was 2 for patients with two or three elevated markers, 1 for those with one elevated marker, and 0 for those no elevated markers. Overall survival (OS) in patients with CTM scores 0, 1, and 2 was 61.8%, 31.4%, and 15.1%, respectively (P<.001). The CTM score independently predicted OS on multivariate analysis (HR, 1.95; 95% CI, 1.73 to 2.21; P<.001). Moreover, the area under the receiver operating characteristics curve of the CTM score (0.67; 95% CI, 0.64 to 0.70) was higher than the values of any individual marker (0.63, 0.57, 0.57; P<.001 for all comparisons). The CTM score independently predicted postoperative survival in GC, and it may have better clinical utility than individual tumor markers for identifying high-risk patients with GC.
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21
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Haraguchi N, Arigami T, Uenosono Y, Yanagita S, Uchikado Y, Mori S, Kurahara H, Kijima Y, Nakajo A, Maemura K, Ishigami S, Natsugoe S. Clinical significance of primary tumor score determined by tumor depth and size in patients with resectable gastric cancer. Oncotarget 2018; 9:8512-8520. [PMID: 29492212 PMCID: PMC5823562 DOI: 10.18632/oncotarget.23953] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Accepted: 11/16/2017] [Indexed: 12/29/2022] Open
Abstract
Although postoperative management of gastric cancer is determined by pathological stage based on the tumor-node-metastasis classification, predicting disease recurrence and prognosis in patients undergoing gastrectomy is clinically difficult. We investigated the depth of tumor invasion and tumor size in resected specimens from patients with gastric cancer and assessed the clinical utility of primary tumor score (PTS) calculated by tumor depth and size as a prognostic marker. We classified 247 patients with gastric cancer into three groups based on cut-off values for deeper tumor invasion (pT2–T4) and larger tumor size (≥ 45 mm) as a PTS of 2 (both abnormalities), 1 (one abnormality), or 0 (neither abnormality). PTS correlated significantly with lymph node metastasis, lymphovascular invasion, and stage (P < 0.0001 each). Survival differences among groups based on PTS were significant (P < 0.0001). Multivariate analysis identified PTS alone as an independent prognostic factor (P = 0.0363). PTS derived from primary tumor information alone is a potentially useful marker for predicting tumor progression and prognosis in postoperative patients with gastric cancer.
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Affiliation(s)
- Naoto Haraguchi
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Takaaki Arigami
- Onco-biological Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yoshikazu Uenosono
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Shigehiro Yanagita
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yasuto Uchikado
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Shinichiro Mori
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Hiroshi Kurahara
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yuko Kijima
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Akihiro Nakajo
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kosei Maemura
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Sumiya Ishigami
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Shoji Natsugoe
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.,Onco-biological Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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22
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Abbas M, Habib M, Naveed M, Karthik K, Dhama K, Shi M, Dingding C. The relevance of gastric cancer biomarkers in prognosis and pre- and post- chemotherapy in clinical practice. Biomed Pharmacother 2017; 95:1082-1090. [DOI: 10.1016/j.biopha.2017.09.032] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Revised: 09/07/2017] [Accepted: 09/08/2017] [Indexed: 02/07/2023] Open
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23
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Yoo MW, Park J, Han HS, Yun YM, Kang JW, Choi DY, Lee JW, Jung JH, Lee KY, Kim KP. Discovery of gastric cancer specific biomarkers by the application of serum proteomics. Proteomics 2017; 17. [PMID: 28133907 DOI: 10.1002/pmic.201600332] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 11/22/2016] [Accepted: 01/26/2017] [Indexed: 11/07/2022]
Abstract
Current diagnostic markers for gastric cancer are not sufficiently specific or sensitive for use in clinical practice. The aims of this study are to compare the proteomes of serum samples from patients with gastric cancers and normal controls, and to develop useful tumor markers of gastric cancer by quantitative proteomic analysis. We identified a total of 388 proteins with a ≤1% FDR and with at least two unique peptides from the sera of each group. Among them, 215, 251, and 260 proteins were identified in serum samples of patients in an advanced cancer group, early cancer group, and normal control group, respectively. We selected differentially expressed proteins in cancer patients compared with those of normal controls via semiquantitative analyses comparing the spectral counts of identified proteins. These differentially expressed proteins were successfully verified using an MS-based quantitative assay, multiple reactions monitoring analysis. Four proteins (vitronectin, clusterin isoform 1, thrombospondin 1, and tyrosine-protein kinase SRMS) were shown to have significant changes between the cancer groups and the normal control group. These four serum proteins were able to discriminate gastric cancer patients from normal controls with sufficient specificity and selectivity.
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Affiliation(s)
- Moon-Won Yoo
- Department of Surgery, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Jisook Park
- Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University, Yong-in City, Republic of Korea
| | - Hye-Seung Han
- Department of Pathology, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Yeo-Min Yun
- Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Jeong Won Kang
- Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University, Yong-in City, Republic of Korea
| | - Do-Young Choi
- Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University, Yong-in City, Republic of Korea
| | - Joon Won Lee
- Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University, Yong-in City, Republic of Korea
| | - Jae Hun Jung
- Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University, Yong-in City, Republic of Korea
| | - Kyung-Yung Lee
- Department of Surgery, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Kwang Pyo Kim
- Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University, Yong-in City, Republic of Korea
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24
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Wu F, Shi C, Wu R, Huang Z, Chen Q. Peritoneal recurrence in gastric cancer following curative resection can be predicted by postoperative but not preoperative biomarkers: a single-institution study of 320 cases. Oncotarget 2017; 8:78120-78132. [PMID: 29100454 PMCID: PMC5652843 DOI: 10.18632/oncotarget.17696] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 02/28/2017] [Indexed: 12/11/2022] Open
Abstract
To determine the risk factors for peritoneal recurrence in gastric cancer patients after curative resection, we included 320 patients with stage I-III primary gastric cancer between January 2008 and June 2012. Data on each patient's surgical and pathological information, preoperative and postoperative tumor markers were collected and analyzed retrospectively. The risk factors for peritoneal recurrence were investigated by univariate and multivariate analysis. In patients with peritoneal recurrence, advanced T or N stage, low differentiation, vascular/lymphatic invasion, perineural invasion, and elevated postoperative CEA/CA19-9 were more common than in patients without peritoneal recurrence. Patients with peritoneal recurrence showed a worse overall survival (OS) compared to those without peritoneal recurrence. In addition, patients with peritoneal recurrence within the first year had a worse OS compared to those with recurrence after 1 year. The univariate and multivariate analyses revealed that elevated number of metastatic lymph nodes and elevated postoperative CEA and CA19-9 were three independent risk factors for peritoneal recurrence in gastric cancer patients. For patients with N3 stage and high postoperative CEA and CA19-9, we found an initial steep slope within approximately 1 year and a subsequent gentle slope in the risk curve. Combined receiver operating characteristic curve analysis using the three independent risk factors for peritoneal recurrence yielded an area under the curve value of 0.73 with 73.7% sensitivity and 64.2% specificity. Therefore, the risk factors may be associated with peritoneal recurrence after curative resection in selected gastric cancer patients.
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Affiliation(s)
- Fan Wu
- The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, PR, China
| | - Chunmei Shi
- Fujian Medical University Union Hospital, Fuzhou, Fujian Province, PR, China.,Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian Province, PR, China
| | - Riping Wu
- The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, PR, China.,Fujian Medical University Union Hospital, Fuzhou, Fujian Province, PR, China
| | - Zhiqing Huang
- The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, PR, China.,Fujian Medical University Stem Cell Research Institute, Fuzhou, Fujian Province, PR, China
| | - Qiang Chen
- The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, PR, China.,Fujian Medical University Stem Cell Research Institute, Fuzhou, Fujian Province, PR, China
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25
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Wang S, Zhao M, Mu R, Zhang X, Yun K, Shang H. Biological variation of serum neuron-specific enolase and carbohydrate antigen 724 tumor markers. J Clin Lab Anal 2017; 32:e22327. [PMID: 28926140 DOI: 10.1002/jcla.22327] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 08/25/2017] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND The aim of our study was to assess two tumor markers, carbohydrate antigen 724 (CA724) and neuron-specific enolase (NSE), in 20 healthy individuals. Then, we determined their average intra- and inter-individual biological variations (CVI and CVG ). METHODS Blood samples were taken at weekly intervals for five weeks from 20 healthy subjects through a detailed questionnaire and physical examination. These samples were stored at -80°C and analyzed in a single run in duplicate. We calculated the biological variations, the reference change value (RCV), and the index of individuality (II) for the two tumor markers. RESULTS The intra-individual and inter-individual biological variations were 50.3% and 103.4% for CA724, and 10.1% and 12.0% for NSE, respectively. The II values for CA724 and NSE were 0.48 and 0.85, respectively. CONCLUSION We determined the biological variations and indices of individuality for CA724 and NSE among 20 healthy subjects. These results will improve clinical applications of the markers.
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Affiliation(s)
- Shuo Wang
- Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, China
| | - Min Zhao
- Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, China
| | - Runqing Mu
- Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, China
| | - Xin Zhang
- Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, China
| | - Ke Yun
- Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, China
| | - Hong Shang
- Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, China
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26
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Wada N, Kurokawa Y, Miyazaki Y, Makino T, Takahashi T, Yamasaki M, Nakajima K, Takiguchi S, Mori M, Doki Y. The characteristics of the serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels in gastric cancer cases. Surg Today 2016; 47:227-232. [PMID: 27566604 DOI: 10.1007/s00595-016-1408-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 05/10/2016] [Indexed: 12/13/2022]
Abstract
PURPOSE Although carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are the most commonly used tumor markers in gastric cancer, the differences in the characteristics of these two markers remain unclear, because most previous studies have included many patients who were positive for both markers. METHODS We analyzed the available data on 1050 patients with gastric cancer who underwent R0 resection. The background characteristics and recurrence-free survivals (RFS) were compared between the single-positive patients for CEA or CA 19-9 and double-negative patients. RESULTS Among these 1050 patients, 86 patients (8.2 %) were positive for CEA only, 77 patients (7.3 %) were positive for CA 19-9 only, and 867 patients (82.6 %) were double negative for both markers. Patients who were elderly, male and had a differentiated histology were more commonly observed in the CEA-positive group than in the double-negative group (P = 0.004, P = 0.009, and P = 0.001). The patients who were positive for either CEA or CA 19-9 had a significantly worse RFS than the patients who were negative for both (P < 0.001 and P < 0.001). The most frequent site of recurrence was the liver (9.3 %) in the CEA-positive group and the peritoneum (11.7 %) in the CA 19-9-positive group. CONCLUSION Age, sex, and histological type were thus found to be associated with CEA positivity. CEA is, therefore, considered to be a sensitive marker for liver recurrence, while CA 19-9 is a sensitive marker for peritoneal recurrence.
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Affiliation(s)
- Noriko Wada
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Yasuhiro Miyazaki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tsuyoshi Takahashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Makoto Yamasaki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kiyokazu Nakajima
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan
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27
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Sluiter N, de Cuba E, Kwakman R, Kazemier G, Meijer G, Te Velde EA. Adhesion molecules in peritoneal dissemination: function, prognostic relevance and therapeutic options. Clin Exp Metastasis 2016; 33:401-16. [PMID: 27074785 PMCID: PMC4884568 DOI: 10.1007/s10585-016-9791-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 04/07/2016] [Indexed: 12/14/2022]
Abstract
Peritoneal dissemination is diagnosed in 10–25 % of colorectal cancer patients. Selected patients are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. For these patients, earlier diagnosis, optimised selection criteria and a personalised approach are warranted. Biomarkers could play a crucial role here. However, little is known about possible candidates. Considering tumour cell adhesion as a key step in peritoneal dissemination, we aim to provide an overview of the functional importance of adhesion molecules in peritoneal dissemination and discuss the prognostic, diagnostic and therapeutic options of these candidate biomarkers. A systematic literature search was conducted according to the PRISMA guidelines. In 132 in vitro, ex vivo and in vivo studies published between 1995 and 2013, we identified twelve possibly relevant adhesion molecules in various cancers that disseminate peritoneally. The most studied molecules in tumour cell adhesion are integrin α2β1, CD44 s and MUC16. Furthermore, L1CAM, EpCAM, MUC1, sLex and Lex, chemokine receptors, Betaig-H3 and uPAR might be of clinical importance. ICAM1 was found to be less relevant in tumour cell adhesion in the context of peritoneal metastases. Based on currently available data, sLea and MUC16 are the most promising prognostic biomarkers for colorectal peritoneal metastases that may help improve patient selection. Different adhesion molecules appear expressed in haematogenous and transcoelomic spread, indicating two different attachment processes. However, our extensive assessment of available literature reveals that knowledge on metastasis-specific genes and their possible candidates is far from complete.
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Affiliation(s)
- Nina Sluiter
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Erienne de Cuba
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.,Department of Pathology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Riom Kwakman
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Gerrit Meijer
- Department of Pathology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.,Department of Pathology, Antoni van Leeuwenhoek Hospital (NKI-AVL), Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Elisabeth Atie Te Velde
- Department of Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. .,Department of Surgical Oncology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
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28
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Chen Y, Wang K, Liu Z, Sun R, Cui D, He J. Rapid detection and quantification of tumor marker carbohydrate antigen 72-4 (CA72-4) using a superparamagnetic immunochromatographic strip. Anal Bioanal Chem 2016; 408:2319-27. [DOI: 10.1007/s00216-016-9328-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Revised: 01/04/2016] [Accepted: 01/12/2016] [Indexed: 02/07/2023]
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29
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Combined fibrinogen concentration and neutrophil-lymphocyte ratio as a prognostic marker of gastric cancer. Oncol Lett 2015; 11:1537-1544. [PMID: 26893776 DOI: 10.3892/ol.2015.4049] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Accepted: 11/05/2015] [Indexed: 12/11/2022] Open
Abstract
Certain patients with early gastric cancer succumb to recurrent disease and cancer-associated complications. The key cause of recurrence is challenging to determine, since clinical blood markers that are able to predict the tumor properties of gastric cancer are limited. The present study investigated the fibrinogen concentration and neutrophil-lymphocyte ratio (NLR) in blood specimens from patients with gastric cancer, and assessed the clinical applicability of combining the fibrinogen concentration with the NLR (CFS-NLR) as a prognostic marker of gastric cancer. The present study consisted of 275 patients with gastric cancer, who were divided into three groups: Those possessing hyperfibrinogenemia (≥305 mg/dl) and a high NLR (≥2.34; CFS-NLR 2 group); those possessing either hyperfibrinogenemia or a high NLR (CFS-NLR 1 group); or those that possessed neither abnormality (CFS-NLR 0 group). The CFS-NLR was significantly associated with the depth of tumor invasion, lymph node metastasis, lymphovascular invasion and tumor stage (P<0.0001). The prognostic differences among the three groups were significant (P=0.0016). Therefore, the CFS-NLR may be a potentially useful blood marker for predicting tumor progression and the prognosis of patients with gastric cancer.
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30
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Clinicopathologic and Prognostic Value of Serum Carbohydrate Antigen 19-9 in Gastric Cancer: A Meta-Analysis. DISEASE MARKERS 2015; 2015:549843. [PMID: 26576068 PMCID: PMC4631884 DOI: 10.1155/2015/549843] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Accepted: 09/29/2015] [Indexed: 12/12/2022]
Abstract
Background. The clinical value of carbohydrate antigen (CA) 19-9 in gastric cancer is controversial. We evaluated the clinicopathologic and prognostic value of CA 19-9 in gastric cancer. Methods. A literature search was conducted in PubMed and Embase databases. Odds ratios (ORs), risk ratios (RR), hazard ratios (HRs), and 95% confidence intervals (CIs) were used as effect measures. Results. Thirty-eight studies were included. Results showed that there were significant differences in the incidence of high CA 19-9 levels between stages III/IV and I/II groups (OR = 3.36; 95% CI = 2.34–4.84), the pT3/T4 and pT1/T2 groups (OR = 2.40; 95% CI = 1.60–3.59), the lymph node-positive and node-negative groups (OR = 2.91; 95% CI = 2.21–3.84), the metastasis-positive and metastasis-negative groups (OR = 2.76; 95% CI = 1.12–6.82), and vessel invasion-positive and invasion-negative groups (OR = 1.66; 95% CI = 1.11–2.48). Moreover, CA 19-9 was significantly associated with poor overall survival (HR = 1.83; 95% CI = 1.56–2.15), disease-free survival (HR = 1.85; 95% CI = 1.16–2.95), and disease-specific survival (HR = 1.33; 95% CI = 1.10–1.60) in gastric cancer. Conclusions. Our meta-analysis showed that CA 19-9 indicates clinicopathologic characteristics of gastric cancer and is associated with a poor prognosis.
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31
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Tang Z, Sheng H, Zheng X, Ying L, Wu L, Liu D, Liu G. Upregulation of circulating cytokeratin 20, urokinase plasminogen activator and C-reactive protein is associated with poor prognosis in gastric cancer. Mol Clin Oncol 2015; 3:1213-1220. [PMID: 26807223 PMCID: PMC4665934 DOI: 10.3892/mco.2015.624] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Accepted: 07/09/2015] [Indexed: 12/21/2022] Open
Abstract
Gastric cancer is one of the most common types of cancer, with a high mortality rate. The aim of this study was to investigate the role of several key molecules, including cytokeratin (CK) 19 and CK20, urokinase plasminogen activator (uPA), C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9, which are involved in cancer invasion and metastasis, in order to determine whether they may be considered as novel prognostic factors for gastric cancer. Peripheral blood was collected from 165 patients with gastric adenocarcinoma who underwent curative surgical resection at Zhejiang Cancer Hospital (Hangzhou, China) between 2010 and 2011. The mRNA levels of CK19, CK20, uPA and MMP-9 were detected by reverse transcription-quantitative polymerase chain reaction. The protein expression of CRP was measured by immunoturbidimetry. The Students t-test was used in the univariate analyses and the Kaplan-Meier method was used to analyze the survival curves. The relative mRNA expression of CK19 and MMP-9 was not found to be significantly associated with gender, age or cancer stage, whereas that of CK20 and uPA was associated with gastric cancer stage: The low-expression group was associated with early-stage and the high-expression group with more advanced-stage disease (P<0.05). The CRP protein level was associated with gender and cancer stage: The low-expression group was predominantly associated with male gender and early-stage disease, whereas the high-expression group was associated with female gender and advanced-stage disease (P<0.05). The expression of CK19, CK20, uPA and CRP, but not MMP-9, was negatively associated with overall survival (OS): The OS rate in the high-expression groups was significantly lower compared with that in the low-expression groups (P<0.05). In conclusion, the upregulation of CK20, uPA and CRP was found to be a negative prognostic factor for gastric cancer.
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Affiliation(s)
- Zhongzhu Tang
- Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China; Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang 310022, P.R. China
| | - Huaying Sheng
- Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Xiao Zheng
- Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Lisha Ying
- Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Lie Wu
- Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China; Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang 310022, P.R. China
| | - Dong Liu
- Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China; Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang 310022, P.R. China
| | - Guan Liu
- Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China; Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang 310022, P.R. China
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32
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Chen Z, Zheng W, Huang P, Tu D, Zhou S, Huang M, Chen X. Lanthanide-doped luminescent nano-bioprobes for the detection of tumor markers. NANOSCALE 2015; 7:4274-4290. [PMID: 25532615 DOI: 10.1039/c4nr05697c] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Sensitive and specific biodetection of tumor markers is essential for early-stage cancer diagnosis and therapy, and will ultimately increase the patient survival rate. As a new generation of luminescent bioprobes, lanthanide (Ln(3+))-doped inorganic luminescent nanoparticles have attracted considerable interest for a variety of biomedical applications due to their superior physicochemical properties. In this feature article, we provide a brief overview of the most recent advances in the development of Ln(3+)-doped luminescent nano-bioprobes and their promising applications for in vitro detection of tumor markers with an emphasis on the establishment of state-of-the-art assay techniques, such as heterogeneous time-resolved (TR) luminescent bioassay, dissolution-enhanced luminescent bioassay, upconversion (UC) luminescent bioassay, homogeneous TR Förster resonance energy transfer (TR-FRET) and UC-FRET bioassays. Some future prospects and efforts towards this emerging field are also envisioned.
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Affiliation(s)
- Zhuo Chen
- Key Laboratory of Optoelectronic Materials Chemistry and Physics, and Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.
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33
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Kim DH, Yun HY, Ryu DH, Han HS, Han JH, Yoon SM, Youn SJ. Preoperative CA 125 is significant indicator of curative resection in gastric cancer patients. World J Gastroenterol 2015; 21:1216-1221. [PMID: 25632195 PMCID: PMC4306166 DOI: 10.3748/wjg.v21.i4.1216] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Revised: 08/20/2014] [Accepted: 09/30/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the correlation among tumor markers, curative resection, and recurrence in gastric cancer.
METHODS: The patients with preoperative tumor makers [Carcinoembryonic antigen, Carbohydrate antigen (CA) 19-9, and CA 125] and elective gastrectomy between January 2000 and December 2009 at Chungbuk National University Hospital were enrolled in this study. We analyzed the relationship among the tumor makers, curative resection and recurrence, retrospectively.
RESULTS: Among the 679 patients with gastric cancer, curative resection was 93.6% (n = 636) and non-curative resection was 6.4% (n = 43). The independent risk factors for the non-curative resection were tumor location and the positivity of preoperative serum CA 19-9 and CA 125 levels. After curative resection, the independent prognostic risk factors for recurrence in curative resection were gender, stage, and preoperative increased serum CA 125 level (HR = 2.431, P =0.020), in a multivariate analysis.
CONCLUSION: Preoperative CA 125 is a useful predictive biomarker for curative resection and prognostic biomarker for recurrence in gastric cancer patients.
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Deng K, Yang L, Hu B, Wu H, Zhu H, Tang C. The prognostic significance of pretreatment serum CEA levels in gastric cancer: a meta-analysis including 14651 patients. PLoS One 2015; 10:e0124151. [PMID: 25879931 PMCID: PMC4400039 DOI: 10.1371/journal.pone.0124151] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Accepted: 03/10/2015] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) is commonly used as a serum tumor marker in clinical practice; however, its prognostic value for gastric cancer patients remains uncertain. This meta-analysis was performed to assess the prognostic value of CEA and investigate CEA as a tumor marker. METHODS PubMed, EMBASE and other databases were searched for potentially eligible studies. Forty-one studies reporting the prognostic effect of pretreatment serum CEA expression in gastric cancer patients were selected. Data on 14651 eligible patients were retrieved for the meta-analysis. Based on the data extracted from the available literature, the hazard ratio (HR) and 95% confidence interval (CI) for an adverse prognosis were estimated for gastric cancer patients with elevated pretreatment serum levels of CEA (CEA+) relative to patients with normal pretreatment CEA levels (CEA-). RESULTS The CEA+ patients had a significantly poorer prognosis than the CEA- patients in terms of overall survival (OS: HR 1.716, 95% CI 1.594 - 1.848, P< 0.001), disease-specific survival (DSS: HR 1.940, 95% CI 1.563 - 2.408, P< 0.001), and disease-free survival (DFS: HR 2.275, 95% CI 1.836 - 2.818, P< 0.001). Publication bias and an influence of different cut-off values were not observed (all P> 0.05). In the pooled analyses of multivariate-adjusted HRs, the results suggested that pretreatment serum CEA may be an independent prognostic factor in gastric cancer (OS: HR 1.681, 95% CI 1.425 - 1.982; DSS: HR 1.900, 95% CI 1.441 - 2.505; DFS: HR 2.579, 95% CI 1.935 - 3.436). CONCLUSION/SIGNIFICANCE The meta-analysis based on the available literature supported the association of elevated pretreatment serum CEA levels with a poor prognosis for gastric cancer and a nearly doubled risk of mortality in gastric cancer patients. CEA may be an independent prognostic factor for gastric cancer patients and may aid in determining appropriate treatment which may preferentially benefit the CEA+ patients.
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Affiliation(s)
- Kai Deng
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Li Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hao Wu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hong Zhu
- Department of Abdominal Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chengwei Tang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- * E-mail:
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Sun Z, Zhang N. Clinical evaluation of CEA, CA19-9, CA72-4 and CA125 in gastric cancer patients with neoadjuvant chemotherapy. World J Surg Oncol 2014; 12:397. [PMID: 25543664 PMCID: PMC4320462 DOI: 10.1186/1477-7819-12-397] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2014] [Accepted: 12/05/2014] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND In the clinical practice of neoadjuvant chemotherapy, response markers are very important. We aimed o investigate whether tumor markers CEA(carcino-embryonic antigen), CA19-9(carbohydrate antigen 19-9), CA72-4(carbohydrate antigen 72-4), and CA125(carbohydrate antigen 125) can be used to evaluate the response to neoadjuvant chemotherapy, and to evaluate the diagnosis and prognosis value of four tumor markers in the patients of gastric cancer. METHODS A retrospective review was performed of 184 gastric cancer patients who underwent a 5-Fu, leucovorin, and oxaliplatin (FOLFOX) neoadjuvant chemotherapy regimen, followed by surgical treatment. Blood samples for CEA, CA19-9, CA72-4, and CA125 levels were taken from patients upon admission to the hospital and after neoadjuvant chemotherapy. Statistical analysis was performed to identify the clinical value of these tumor markers in predicting the survival and the response to neoadjuvant chemotherapy. RESULTS Median overall survival times of pretreatment CA19-9-positive and CA72-4-positive patients (14.0 +/-2.8 months and 14.8 +/-4.0 months, respectively) were significantly less than negative patients (32.5 +/-8.9 months and 34.0 +/-10.1 months, respectively) (P = 0.000 and P = 0.002, respectively). Pretreatment status of CA19-9 and CA72-4 were independent prognostic factors in gastric cancer patients (P = 0.029 and P = 0.008, respectively). Pretreatment CEA >50 ng/ml had a positive prediction value for clinical disease progression after neoadjuvant chemotherapy according to the ROC curve (AUC: 0.694, 95% CI: 0.517 to 0.871, P = 0.017). The decrease of tumor markers CEA, CA72-4, and CA125 was significant after neoadjuvant chemotherapy (P = 0.030, P = 0.010, and P = 0.009, respectively), especially in patients with disease control (including complete, partial clinical response, and stable disease) (P = 0.012, P = 0.020, and P = 0.025, respectively). A decrease in CA72-4 by more than 70% had a positive prediction value for pathologic response to neoadjuvant chemotherapy according to the ROC curve (AUC: 0.764, 95% CI: 0.584 to 0.945, P = 0.020). CONCLUSIONS Our results suggest that high preoperative serum levels of CA72-4 and CA19-9 are associated with higher risk of death, high pretreatment CEA levels (>50 ng/ml) may predict clinical disease progression after neoadjuvant chemotherapy, and a decrease (>70%) of CA72-4 may predict pathologic response to neoadjuvant chemotherapy.
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Affiliation(s)
| | - Nengwei Zhang
- Beijing Shijitan Hospital, Capital Medical University, Room 334, Administrative Building, Beijing 100038, China.
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Lee EC, Yang JY, Lee KG, Oh SY, Suh YS, Kong SH, Yang HK, Lee HJ. The value of postoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels for the early detection of gastric cancer recurrence after curative resection. J Gastric Cancer 2014; 14:221-8. [PMID: 25580353 PMCID: PMC4286900 DOI: 10.5230/jgc.2014.14.4.221] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 10/04/2014] [Accepted: 10/05/2014] [Indexed: 12/15/2022] Open
Abstract
PURPOSE This study aimed to evaluate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels to detect gastric cancer recurrence. MATERIALS AND METHODS We retrospectively reviewed 154 patients who developed recurrence within 2 years after curative gastric cancer surgery and analyzed the relationship between postoperative CEA and CA19-9 levels and recurrence. We readjusted the cut-off values to improve the detection of recurrence. Subgroup analysis according to clinicopathologic variables was performed to further investigate the relationship between recurrence and CEA and CA19-9 levels. RESULTS The sensitivity and specificity for elevated CEA levels to detect recurrence were 40.6% and 89.5%, respectively, and those for CA19-9 were 34.2% and 93.6%, respectively. The sensitivity and specificity for elevation of either tumor marker were 54.3% and 84.0%, respectively; those for elevation of both tumor markers were 19.2% and 98.4%, respectively. By readjusting the cut-off values from 5.0 ng/ml to 5.2 ng/ml for CEA and from 37.00 U/ml to 30.0 U/ml for CA19-9, the sensitivity was increased from 34.2% to 40.2% for CA19-9, while there was no increase in sensitivity for CEA. In subgroup analysis, the sensitivity of CEA was higher in patients with elevated preoperative CEA levels than in patients with normal preoperative CEA levels (86.7% versus 33.7%; P<0.001). Furthermore, the sensitivity of CA19-9 was higher in patients with elevated preoperative CA19-9 levels than in patients with normal preoperative CA19-9 levels (82.61% versus 26.83%; P<0.001). CONCLUSIONS CEA and/or CA19-9 measurement with the readjusted cut-off values allows for more effective detection of gastric cancer recurrence.
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Affiliation(s)
- Eung-Chang Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jun-Young Yang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Goo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Seung-Young Oh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Yun-Suhk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Seong-Ho Kong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Han-Kwang Yang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. ; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyuk-Joon Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. ; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Prognostic value of carbohydrate tumor markers and inflammation-based markers in metastatic or recurrent gastric cancer. Med Oncol 2014; 31:289. [PMID: 25344872 DOI: 10.1007/s12032-014-0289-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2014] [Accepted: 10/11/2014] [Indexed: 12/18/2022]
Abstract
We examined the relationship between hematological parameters and clinicopathologic significance in metastatic or recurrent gastric cancer (MRGC) patients, and construct a prognostic index for MRGC patients. We retrospectively reviewed the medical records of 439 patients with MRGC. Tumor markers, inflammation-based markers such as mGPS (which combines CRP and albumin concentrations), NLR, PLR and other hematological parameters were observed in the study. CA125 was more frequently positive with peritoneal recurrence, and CEA was more frequently positive in patients with liver metastases. In the univariate analysis of survival, the following variables were associated with shorter overall survival (OS): male, previous pathology such as nerves invasion and vessel invasion, elevated CEA, CA72-4, CA125 and CA19-9, and inflammation-based variables such as Alb, CRP, mGPS, PLR, NLR, Hb, LDH, AchE and AKP. In the multivariate analysis, mGPS, CEA and CA125 were independent prognostic factors for OS. An exploration of the potential prognostic index model including the three independent factors was carried out, MSTs for the low-, moderate- and high-risk groups were 12, 10.5 and 5 months. Elevated serum CEA, CA125 and mGPS in patients with MRGC are independent negative predictor of prognosis. And the prognostic index was constructed to predict prognosis of MRGC patients more accurately.
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D’Angelo G, Rienzo TD, Ojetti V. Microarray analysis in gastric cancer: A review. World J Gastroenterol 2014; 20:11972-11976. [PMID: 25232233 PMCID: PMC4161784 DOI: 10.3748/wjg.v20.i34.11972] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2013] [Revised: 01/03/2014] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is one of the most common tumors worldwide. Although several treatment options have been developed, the mortality rate is increasing. Lymph node involvement is considered the most reliable prognostic indicator in gastric cancer. Early diagnosis improves the survival rate of patients and increases the likelihood of successful treatment. The most reliable diagnostic method is endoscopic examination, however, it is expensive and not feasible in poorer countries. Therefore, many innovative techniques have been studied to develop a new non-invasive screening test and to identify specific serum biomarkers. DNA microarray analysis is one of the new technologies able to measure the expression levels of a large number of genes simultaneously. It is possible to define the gene expression profile of the tumor and to correlate it with the prognosis and metastasis formation. Several studies in the literature have been published on the role of microarray analysis in gastric cancer and the mechanisms of proliferation and metastasis formation. The aim of this review is to analyze the importance of microarray analysis and its clinical applications to better define the genetic characteristics of gastric cancer and its possible implications in a more decisive treatment.
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Abstract
OBJECTIVE To construct and verify a diagnostic model using proteomic analysis of serum samples for identifying gastric precancerous lesions and gastric cancer (GC). METHODS The serum samples from 25 patients with gastric precancerous lesions (chronic atrophic gastritis with mild to moderate dysplasia), 25 GC patients and 25 healthy controls were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Spectral peaks with significant difference among the groups were identified and used as a diagnostic model for detecting gastric precancerous lesions and GC. The serum peptide map model was validated using an independent sample set including 15 healthy volunteers, 15 precancerous and 15 GC patients. RESULTS The spectral peaks for the peptides with mass-to-charge (m/z) values of 1741 and 4210 were the most significantly different among the three groups. The sensitivity of this diagnostic model for detecting healthy controls, patients with gastric precancerous lesions and patients with GC was 80.0% (12/15), 66.7% (10/15) and 66.7% (10/15) respectively, while the specificity was 66.7% (20/30), 73.3% (22/30) and 73.3% (22/30), respectively. CONCLUSION Our diagnostic model is useful for diagnosing gastric precancerous lesions and GC.
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Affiliation(s)
- Peng Li
- Department of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing Digestive Diseases Center
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Xiao J, He X, Wang Z, Hu J, Sun F, Qi F, Yang S, Xiao Z. Serum carbohydrate antigen 19-9 and prognosis of patients with gastric cancer. Tumour Biol 2014; 35:1331-4. [PMID: 24234331 DOI: 10.1007/s13277-013-1177-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Accepted: 09/02/2013] [Indexed: 12/25/2022] Open
Abstract
Previous studies have assessed the prognostic role of serum carbohydrate antigen 19-9 (CA 19-9) concentration in patients with gastric cancer, but the findings from those studies were inconsistent. We searched the PubMed and Web of Science databases to find eligible studies assessing the prognostic role of CA 19-9 in patients with gastric cancer. Twelve studies with a total of 5,072 gastric cancer patients were finally included into the meta-analysis. The pooled hazard ratio (HR) with corresponding 95 % confidence interval (95 % CI) for overall survival were calculated to assess the prognostic role of CA 19-9 in patients with gastric cancer. Overall, elevated serum concentration of CA 19-9 (>37 U/mL) was associated with poorer overall survival in patients with gastric cancer (fixed-effects HR = 1.36, 95 % CI 1.24-1.48, P < 0.001). Subgroup analysis by study design further showed that elevated serum concentration of CA 19-9 was associated with poorer overall survival in patients with gastric cancer. There was no obvious risk of publication bias. Elevated concentration of serum CA 19-9 is associated with poorer overall survival in patients with gastric cancer.
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Shimada H, Noie T, Ohashi M, Oba K, Takahashi Y. Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association. Gastric Cancer 2014; 17:26-33. [PMID: 23572188 DOI: 10.1007/s10120-013-0259-5] [Citation(s) in RCA: 352] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2012] [Accepted: 03/24/2013] [Indexed: 02/06/2023]
Abstract
The aim of this review was to evaluate the clinical significance of serum tumor markers, particularly CEA, CA19-9, and CA72-4, in patients with gastric cancer. A systematic literature search was performed using PubMed/MEDLINE with the keywords "gastric cancer" and "tumor marker," to select 4,925 relevant reports published before the end of November 2012. A total of 187 publications contained data for CEA and CA19-9, and 19 publications contained data related to all three tumor markers. The positive rates were 21.1 % for CEA, 27.8 % for CA19-9, and 30.0 % for CA72-4. These three markers were significantly associated with tumor stage and patient survival. Serum markers are not useful for early cancer, but they are useful for detecting recurrence and distant metastasis, predicting patient survival, and monitoring after surgery. Tumor marker monitoring may be useful for patients after surgery because the positive conversion of tumor markers usually occurs 2-3 months before imaging abnormalities. Among other tumor markers, alpha-fetoprotein (AFP) is useful for detecting and predicting liver metastases. Moreover, CA125 and sialyl Tn antigens (STN) are useful for detecting peritoneal metastases. Although no prospective trial has yet been completed to evaluate the clinical significance of these serum markers, this literature survey suggests that combinations of CEA, CA19-9, and CA72-4 are the most effective ways for staging before surgery or chemotherapy. In particular, monitoring tumor markers that were elevated before surgery or chemotherapy could be useful for detection of recurrence or evaluation of the response.
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Affiliation(s)
- Hideaki Shimada
- Department of Surgery, School of Medicine, Toho University, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan,
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Liu L, Yan B, Huang J, Gu Q, Wang L, Fang M, Jiao J, Yue X. The identification and characterization of novel N-glycan-based biomarkers in gastric cancer. PLoS One 2013; 8:e77821. [PMID: 24147084 PMCID: PMC3798316 DOI: 10.1371/journal.pone.0077821] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Accepted: 09/04/2013] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND AND AIMS To identify and validate N-glycan biomarkers in gastric cancer (GC) and to elucidate their underlying molecular mechanism of action. METHODS In total, 347 individuals, including patients with GC (gastric cancer) or atrophic gastritis and healthy controls, were randomly divided into a training group (n=287) and a retrospective validation group (n=60). Serum N-glycan profiling was achieved with DNA sequencer-assisted/fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Two diagnostic models were constructed based on the N-glycan profiles using logistic stepwise regression. The diagnostic performance of each model was assessed in retrospective, prospective (n=60), and follow-up (n=40) cohorts. Lectin blotting was performed to determine total core-fucosylation, and the expression of genes involved in core-fucosylation in GC was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS We identified at least 9 N-glycan structures (peaks) and the levels of core fucose residues and fucosyltransferase were significantly decreased in GC. Two diagnostic models, designated GCglycoA and GCglycoB, were constructed to differentiate GC from control and atrophic gastritis. The areas under the receiver operating characteristic (ROC) curves (AUC) for both GCglycoA and GCglycoB were higher than those for CEA, CA19-9, CA125 and CA72-4. Compared with CEA, CA19-9, CA125 and CA72-4, the sensitivity of GCglycoA increased 29.66%, 37.28%, 56.78% and 61.86%, respectively, and the accuracy increased 10.62%, 16.82%, 25.67% and 28.76%, respectively. For GCglycoB, the sensitivity increased 27.97%, 35.59%, 55.09% and 60.17% and the accuracy increased 21.26%, 24.64%, 31.40% and 34.30% compared with CEA, CA19-9, CA125 and CA72-4, respectively. After curative surgery, the core fucosylated peak (peak 3) and the total core fucosylated N-glycans (sumfuc) were reversed. CONCLUSIONS The results indicated that the diagnostic models based on N-glycan markers are valuable and noninvasive alternatives for identifying GC. We concluded that decreased core-fucosylation in both tissue and serum from GC patients may result from the decreased expression of fucosyltransferase.
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Affiliation(s)
- Long Liu
- Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Bing Yan
- Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Junlong Huang
- Department of Nautical Medicine, Laboratory of Stress Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Qunhao Gu
- Department of General Surgery, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lina Wang
- Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Meng Fang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jianpeng Jiao
- Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Xiaoqiang Yue
- Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China
- * E-mail:
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Choi AR, Park JC, Kim JH, Shin SK, Lee SK, Lee YC, Chung JB. High level of preoperative carbohydrate antigen 19-9 is a poor survival predictor in gastric cancer. World J Gastroenterol 2013; 19:5302-5308. [PMID: 23983433 PMCID: PMC3752564 DOI: 10.3748/wjg.v19.i32.5302] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Revised: 07/10/2013] [Accepted: 07/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the clinical significance and the prognostic value of preoperative serum carbohydrate antigen 19-9 (CA 19-9) level in gastric cancer.
METHODS: Between January 2005 and December 2006, 1960 patients underwent surgery for histologically confirmed gastric cancer. Of these, 163 patients had elevated serum levels of CA 19-9 preoperatively, and 1628 patients had normal serum levels of CA 19-9 preoperatively. For this study, 325 patients were selected from the group of 1628 patients by age, sex, and cancer stage to serve as controls. Statistically significant differences in survival rates were calculated using the log-rank test. A P value less than 0.05 was considered statistically significant and was determined using SAS software.
RESULTS: The baseline characteristics showed some differences between the two groups with regard to histology. Overall survival (OS) in the elevated and non-elevated group was 37.90 and 68.67 mo, respectively (P < 0.001). N stage (P = 0.001) was a significant predictor of disease-free survival by multivariate analysis. Also, N stage (P < 0.001), and the presence of peritoneal metastasis (P < 0.001) remained independent factors in predicting OS by multivariate analysis. Additionally, preoperative serum CA 19-9 levels were significantly associated with OS in univariate (P = 0.009) and multivariate (P = 0.021) analyses.
CONCLUSION: Serum CA 19-9 can be considered an independent prognostic factor in predicting OS in patients anticipating surgery for gastric cancer.
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Hultman B, Lind P, Glimelius B, Sundbom M, Nygren P, Haglund U, Mahteme H. Phase II study of patients with peritoneal carcinomatosis from gastric cancer treated with preoperative systemic chemotherapy followed by peritonectomy and intraperitoneal chemotherapy. Acta Oncol 2013; 52:824-30. [PMID: 22974074 DOI: 10.3109/0284186x.2012.702925] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) in patients with peritoneal carcinomatosis (PC) from gastric cancer. MATERIAL AND METHODS Eighteen patients (median age 57 years, range 38-74) were scheduled for three months' neoadjuvant systemic chemotherapy followed by CRS + HIPEC + EPIC. RESULTS At the time of surgery, the peritoneal tumor burden was extensive with tumor growth on the entire peritoneal cavity. Only eight patients received the entire treatment and OS was 14.3 months (range 6.1-34.3, 95% CI 6.6-20.3). Six patients had macroscopically radical (CC0) surgery and for this subgroup OS was 19.1 months (range 6.1-34.3, 95% CI 6.9-27.1). Postoperative 90-day mortality was 10% (one patient) and the perioperative grades II-IV adverse events (AE) rate was 62.5%. DISCUSSION Neoadjuvant chemotherapy followed by CRS + HIPEC + EPIC does not seem to be associated with prolonged OS in patients with extensive PC growth from gastric cancer unless macroscopically radical surgery is achieved. However, morbidity from this treatment is considerable and it cannot be recommended for routine care until a prospective randomized trial has been performed.
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Affiliation(s)
- Bo Hultman
- Department of Surgical Sciences, Section of Surgery, Uppsala University, Uppsala, Sweden.
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Wang YY, Li L, Zhao ZS, Wang HJ. Clinical utility of measuring expression levels of KAP1, TIMP1 and STC2 in peripheral blood of patients with gastric cancer. World J Surg Oncol 2013; 11:81. [PMID: 23548070 PMCID: PMC3620905 DOI: 10.1186/1477-7819-11-81] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2012] [Accepted: 03/09/2013] [Indexed: 12/18/2022] Open
Abstract
Background We examined preoperative kinesin II-associated protein (KAP1), TIMP metallopeptidase inhibitor 1 (TIMP1) and stanniocalcin 2 (STC2) expression levels in patients with gastric cancers to assess their clinical application for diagnosing and monitoring diseases. Methods Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of KAP1, TIMP1, STC2, talin 2 (TLN2), sushi-repeat-containing protein, X-linked 2 (SRPX2) and secreted protein, acidic, cysteine-rich (SPARC) in the patients’ peripheral blood karyocytes. The data were analyzed with receiver operating characteristics (ROC) curves. Results A total of 112 patients with gastric cancer, 42 patients with recurrence and 107 healthy volunteers were recruited. There were significant correlations between KAP1, TIMP1 and STC2 levels, and TNM tumor stages and distant metastases. The area under the ROC curves (AUC) of KAP1 was 0.803 ± 0.040 (P = 0.0001), the AUC of TIMP1 was 0.767 ± 0.043 (P = 0.0001) and the AUC of STC2 was 0.769 ± 0.045 (P = 0.0001), thus differentiating preoperative gastric cancer patients from healthy volunteers by ROC curve analysis. The AUC of STC2 was 0.739 ± 0.070 (P = 0.004) and the AUC of KAP1 was 0.418 ± 0.088 (P = 0.319), thus differentiating recurrence of gastric cancer from healthy volunteers by ROC curve analysis. High TIMP1 and STC2 expression levels were suspected to be poor prognostic factors of disease recurrence in patients with gastric cancer. Conclusions KAP1, TIMP1 and STC2 expression levels may be potential biomarkers for the screening, diagnosis, prognosis and surveillance of gastric cancer.
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Affiliation(s)
- Yuan-Yu Wang
- Department of Pathology, Zhejiang Provincial People's Hospital, 158 shangtang road, Hangzhou, Zhejiang, 310014, PR China
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Chen S, Feng XY, Li YF, Zhao BW, Zhou ZW, Chen YB. The prognosis of gastric cancer patients with marginally elevated carcinoembryonic antigen (CEA) values after D2 radical gastrectomy. J Surg Oncol 2013; 107:641-5. [PMID: 23297055 DOI: 10.1002/jso.23300] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2012] [Accepted: 11/12/2012] [Indexed: 01/13/2023]
Abstract
AIM To investigate the clinical significance of the postoperative serum carcinoembryonic antigen (CEA) levels in gastric cancer patients who underwent D2 radical gastrectomy and to identify the prognostic factors for patients with marginally elevated postoperative CEA levels. METHODS We performed a retrospective study of 480 patients who were histologically diagnosed with gastric cancer and who underwent D2 radical surgery at the Sun Yat-sen University Cancer Center between January 2004 and December 2009. The follow-up lasted until June 2011. Chi-squared tests and Kaplan-Meier methods were employed to compare the adverse events and prognoses. RESULTS In this group of gastric cancer patients, the postoperative serum CEA level (P = 0.002) was an independent prognostic factor; the same was true for the histological T and N staging (P < 0.001 and P = 0.045, respectively). In the group of marginally elevated postoperative CEA level gastric cancer patients, univariate analysis demonstrated that tumor position (P = 0.042); histological grade (P = 0.002); and Boarrmann type (P = 0.003) were significant prognostic factors. Multivariate analysis showed that the tumor position (P = 0.003) and histological grade (P = 0.007) were independent prognostic factors for these patients. CONCLUSION Our study showed that patients with normal postoperative CEA levels have a better prognosis. Furthermore, for marginally elevated postoperative CEA level gastric cancer patients, the tumor position and histological grade were two important factors for predicting the prognosis and the need for aggressive therapy.
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Affiliation(s)
- Shi Chen
- Department of Gastropancreatic Surgery, Sun Yat-Sen University Cancer Center, Guangdong, PR China
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Li X, Lu J, Ren H, Chen T, Gao L, DI L, Song Z, Zhang Y, Yang T, Thakur A, Zhou SF, Yin Y, Chen M. Combining multiple serum biomarkers in tumor diagnosis: A clinical assessment. Mol Clin Oncol 2013; 1:153-160. [PMID: 24649139 PMCID: PMC3956235 DOI: 10.3892/mco.2012.23] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2012] [Accepted: 08/20/2012] [Indexed: 11/06/2022] Open
Abstract
The present study aimed to assess the diagnostic/prognostic value of various clinical tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 (CYFRA21-1), α-fetoprotein (AFP), carbohydrate antigen-125 (CA-125), carbohydrate antigen-19.9 (CA-19.9) and ferritin, individually or in combination. The electro-chemiluminescence immunization method was performed to detect the levels of seven tumor markers in 560 cancer patients and 103 healthy subjects for comparison. The serum levels of the seven markers measured in cancer patients were higher compared to healthy subjects (P<0.05 for AFP and P<0.001 for the remaining six markers). Different markers had different sensitivity towards different types of tumors. Combining more markers significantly increased the ratios of positive diagnosis in the tumors. The diagnostic sensitivities of combining seven markers were particularly high in digestive, urinary and skeletal tumors (82, 92 and 83%, respectively). Gynecological tumors have exhibited a constant yet relatively low positive diagnosis irrespective of the use of a single marker or combined markers. However, the increase in sensitivity when combining markers was accompanied by a decrease in specificity. Generally, combining more markers increased the tumor detection rates, while a combination of the seven markers provided the highest detection rate. Combined detection showed a particularly high sensitivity in detecting respiratory, digestive and urinary system tumors, with the lowest sensitivity observed in gynecological tumors. As a result, combining tumor markers may play an important role in early tumor detection/diagnosis while the loss of specificity can be tolerated.
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Affiliation(s)
- Xin Li
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Jun Lu
- School of Interdisciplinary Health Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1142, New Zealand
| | - Hui Ren
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Tianjun Chen
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Lin Gao
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Ligai DI
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Zhucui Song
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Ying Zhang
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Tian Yang
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Asmitananda Thakur
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Shu-Feng Zhou
- College of Pharmacy, University of South Florida, Tampa, FL 33612, USA
| | - Yanhai Yin
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
| | - Mingwei Chen
- Department of Respiratory Medicine, The First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
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Jo JC, Ryu MH, Koo DH, Ryoo BY, Kim HJ, Kim TW, Choi KD, Lee GH, Jung HY, Yook JH, Oh ST, Kim BS, Kim JH, Kang YK. Serum CA 19-9 as a prognostic factor in patients with metastatic gastric cancer. Asia Pac J Clin Oncol 2012; 9:324-30. [PMID: 23176400 DOI: 10.1111/ajco.12019] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2012] [Indexed: 12/13/2022]
Abstract
AIM To evaluate tumor markers as prognostic factors in patients with metastatic or recurrent gastric cancer receiving first-line chemotherapy. METHODS Between January 2000 and December 2008, 1178 patients with metastatic or recurrent gastric cancer were assayed for expression of three serum tumor markers, CA 19-9, CA 72-4 and carcinoembryonic antigen (CEA), prior to the initiation of first-line chemotherapy. RESULTS Elevated serum concentrations of carbohydrate antigen (CA) 19-9 (>37 U/mL), CA 72-4 (>4 U/mL) and carcinoembryonic antigen (CEA) (>6 ng/mL) were observed in 38, 56 and 33% of patients, respectively. Univariate analysis showed that elevated serum concentration of each of the three markers, CA 19-9 (P = 0.001), CA 72-4 (P = 0.001) and CEA (P = 0.030), was significantly associated with poor patient prognosis. However, multivariate analysis showed that an elevated CA 19-9 concentration only was significantly associated with shorter survival (hazard ratio [HR] 1.22; 95% CI, 1.08-1.37, P = 0.002). In the good risk and moderate risk groups, previously defined by clinical factors alone, survival was significantly lower in patients with elevated CA 19-9 (P < 0.001 and P = 0.021, respectively), but this difference was not observed in the poor-risk group. CONCLUSION Elevated serum CA 19-9 concentration in patients with metastatic or recurrent gastric cancer, especially in good or moderate risk groups, is an independent negative predictor of prognosis.
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Affiliation(s)
- Jae-Cheol Jo
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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Liu X, Cai H, Wang Y. Prognostic significance of tumour markers in Chinese patients with gastric cancer. ANZ J Surg 2012; 84:448-53. [PMID: 23013163 DOI: 10.1111/j.1445-2197.2012.06287.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/11/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND OBJECTIVES The clinical value of preoperative tumour markers remains elusive in gastric cancer. The aim of this study was to investigate the prognostic value of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, CA50 and CA72-4 in gastric cancer. METHODS About 391 gastric cancer patients who underwent curative D2 gastrectomy between 2001 and 2006 were evaluated. The correlation between tumour markers and clinicopathologic characteristics and prognostic value of preoperative tumour markers was investigated. RESULTS Correlation analysis showed that AFP was associated with tumour size (P = 0.040); CEA with lymphatic invasion (P = 0.023) and pathological stage (P = 0.018); CA19-9 with tumour size (P = 0.000), Borrmann type (P = 0.027), lymphatic invasion (P = 0.020) and pathological stage (P = 0.001); CA50 with lymphatic invasion (P = 0.004) and pathological stage (P = 0.004); CA72-4 with tumour size (P = 0.000), tumour size (P = 0.000) and Borrmann type (P = 0.008); lymphatic invasion (P = 0.000), nervous invasion (P = 0.028) and pathological stage (P = 0.000). Multivariate analysis showed that CEA, tumour site, Borrmann type and pathological stage were independent prognostic factors. CONCLUSIONS Preoperative CEA might be a candidate for the staging system in addition to conventional factors.
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Affiliation(s)
- Xiaowen Liu
- Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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Chen XZ, Zhang WK, Yang K, Wang LL, Liu J, Wang L, Hu JK, Zhang B, Chen ZX, Chen JP, Zhou ZG, Mo XM. Correlation between serum CA724 and gastric cancer: multiple analyses based on Chinese population. Mol Biol Rep 2012; 39:9031-9. [PMID: 22752725 DOI: 10.1007/s11033-012-1774-x] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Accepted: 06/09/2012] [Indexed: 02/08/2023]
Abstract
Serum tumor biomarker carbohydrate antigen 724 (CA724) is noticeable for gastric cancer. Correlation between CA724 and gastric cancer was investigated based on Chinese population. Chinese Biomedical Database, Chinese Journal Full-text Database and PubMed were searched. Gastric cancer patients were proven by biopsy, and control included health volunteers or benign gastric diseases. Participants received at least one test of CA724, CA125, CA153, CA199, CA242 or CEA. Meta-analysis, summary ROC (SROC) and post hoc analysis were performed by RevMan 5.0 and SPSS 11.5. Totally, 33 eligible studies were analyzed. Meta-analysis showed CA724 had the highest odds ratio 32.86 compared to control, orderly followed by CA242, CA199, CEA, CA125 and CA153. Accumulated accuracy rate of CA724 was 77 %, superior to others. In SROC analysis, specificity of all studies was above 0.70, but sensitivity of few studies was above 0.70; CA724 was selected as the preferable single test, followed by CA242, CA199, CEA, CA125 and CA153. If threshold of both specificity and sensitivity up to 0.70, CA153 was unacceptable; if up to 0.80, only CA724 and CA242 were considerable. In CA724-combined patterns, CA724+CEA+CA199 combination performed best by increasing sensitivity to 0.74 without impairing specificity, while CA724 + CA199 pattern was not a proper combination. CA724 was the most correlative serum tumor biomarker for gastric cancer in Chinese population. Sensitivity of serum CA724 is limited, but CA724+CEA+CA199 combination is considerable to improve sensitivity without impairing specificity.
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Affiliation(s)
- Xin-Zu Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Guo Xue Xiang, No. 37, Chengdu 610041, Sichuan, China
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