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Chen YN, Shih CY, Guo SL, Liu CY, Shen MH, Chang SC, Ku WC, Huang CC, Huang CJ. Potential prognostic and predictive value of UBE2N, IMPDH1, DYNC1LI1 and HRASLS2 in colorectal cancer stool specimens. Biomed Rep 2023; 18:22. [PMID: 36846616 PMCID: PMC9945078 DOI: 10.3892/br.2023.1604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 12/20/2022] [Indexed: 02/10/2023] Open
Abstract
Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide. The poor specificity and sensitivity of the fecal occult blood test has prompted the development of CRC-related genetic markers for CRC screening and treatment. Gene expression profiles in stool specimens are effective, sensitive and clinically applicable. Herein, a novel advantage of using cells shed from the colon is presented for cost-effective CRC screening. Molecular panels were generated through a series of leave-one-out cross-validation and discriminant analyses. A logistic regression model following reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry was used to validate a specific panel for CRC prediction. The panel, consisting of ubiquitin-conjugating enzyme E2 N (UBE2N), inosine monophosphate dehydrogenase 1 (IMPDH1), dynein cytoplasmic 1 light intermediate chain 1 (DYNC1LI1) and phospholipase A and acyltransferase 2 (HRASLS2), accurately recognized patients with CRC and could thus be further investigated as a potential prognostic and predictive biomarker for CRC. UBE2N, IMPDH1 and DYNC1LI1 expression levels were upregulated and HRASLS2 expression was downregulated in CRC tissues. The predictive power of the panel was 96.6% [95% confidence interval (CI), 88.1-99.6%] sensitivity and 89.7% (95% CI, 72.6-97.8%) specificity at a predicted cut-off value at 0.540, suggesting that this four-gene panel testing of stool specimens can faithfully mirror the state of the colon. On the whole, the present study demonstrates that screening for CRC or cancer detection in stool specimens collected non-invasively does not require the inclusion of an excessive number of genes, and colonic defects can be identified via the detection of an aberrant protein in the mucosa or submucosa.
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Affiliation(s)
- Yu-Nung Chen
- Division of Colorectal Surgery, Department of Surgery, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C
| | - Cheng-Yen Shih
- Division of Gastroenterology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C
| | - Shu-Lin Guo
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.,Department of Anesthesiology, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C,Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei 11490, Taiwan, R.O.C
| | - Chih-Yi Liu
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.,Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 22174, Taiwan, R.O.C
| | - Ming-Hung Shen
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.,Department of Surgery, Fu Jen Catholic University Hospital, New Taipei 24352, Taiwan, R.O.C.,PhD Program in Nutrition and Food Science, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C
| | - Shih-Chang Chang
- Division of Colorectal Surgery, Department of Surgery, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C
| | - Wei-Chi Ku
- School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C
| | - Chi-Cheng Huang
- Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.,Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10090, Taiwan, R.O.C.,Correspondence to: Dr Chi-Cheng Huang, Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Taipei 11217, Taiwan, R.O.C.
| | - Chi-Jung Huang
- Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.,Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan, R.O.C.,Correspondence to: Dr Chi-Cheng Huang, Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Road, Taipei 11217, Taiwan, R.O.C.
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Cao Y, Zhao G, Yuan M, Liu X, Ma Y, Cao Y, Miao B, Zhao S, Li D, Xiong S, Zheng M, Fei S. KCNQ5 and C9orf50 Methylation in Stool DNA for Early Detection of Colorectal Cancer. Front Oncol 2021; 10:621295. [PMID: 33585248 PMCID: PMC7878552 DOI: 10.3389/fonc.2020.621295] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 12/14/2020] [Indexed: 12/24/2022] Open
Abstract
Background Aberrant DNA methylation has emerged as a class of promising biomarkers for early colorectal cancer (CRC) detection, but the performance of methylated C9orf50 and methylated KCNQ5 in stool DNA has never been evaluated. Methods Methylation specific quantitative PCR (qPCR) assays for methylated C9orf50 and methylated KCNQ5 were developed. The methylation levels of C9orf50 and KCNQ5 in 198 CRC patients, 20 advanced adenoma (AA) patients, 101 small polyp (SP) patients, and 141 no evidence of disease (NED) subjects were analyzed. Results The methylation levels of both KCNQ5 and C9orf50 genes were significantly higher in CRC and AA groups than those in SP and NED groups, but showed no significant difference among different stages of CRC. The sensitivities of methylated KCNQ5 and methylated C9orf50 for CRC detection were 77.3% (95% CI: 70.7–82.8%) and 85.9% (95% CI: 80.0–90.2%) with specificities of 91.5% (95% CI: 85.3–95.3%) and 95.0% (95% CI: 89.7–97.8%), respectively. When C9orf50 and methylated KCNQ5 were combined, the clinical performance for CRC detection was similar to that of methylated C9orf50 alone. Conclusions Stool DNA based methylated C9orf50 test has the potential to become an alternative approach for CRC screening and prevention.
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Affiliation(s)
- Yaping Cao
- Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China
| | - Guodong Zhao
- Zhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan, China.,State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.,Department of R&D, Suzhou VersaBio Technologies Co. Ltd., Kunshan, China
| | - Mufa Yuan
- Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China
| | - Xiaoyu Liu
- Zhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan, China
| | - Yong Ma
- Zhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan, China.,Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China
| | - Yang Cao
- Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China
| | - Bei Miao
- Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China
| | - Shuyan Zhao
- Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China
| | - Danning Li
- Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China
| | - Shangmin Xiong
- Zhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan, China.,Department of R&D, Suzhou VersaBio Technologies Co. Ltd., Kunshan, China
| | - Minxue Zheng
- Zhejiang University Kunshan Biotechnology Laboratory, Zhejiang University Kunshan Innovation Institute, Kunshan, China.,Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China
| | - Sujuan Fei
- Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.,Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China
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Gong W, Tian M, Qiu H, Yang Z. Elevated serum level of lncRNA-HIF1A-AS1 as a novel diagnostic predictor for worse prognosis in colorectal carcinoma. Cancer Biomark 2018; 20:417-424. [PMID: 28946548 DOI: 10.3233/cbm-170179] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
To evaluate the diagnostic efficacy and prognostic value of serum long non-coding RNA (lncRNA) HIF 1alpha-antisense RNA 1 (HIF1A-AS1) in patients with colorectal carcinoma (CRC). We obtained serum samples from 151 CRC patients and 160 health controls. Serum level of HIF1A-AS1 was detected via real-time PCR (RT-PCR). Receiver operating characteristics (ROC) curve analysis was conducted to determine the diagnostic value of HIF1A-AS1. Then HIF1A-AS1 in CRC was divided into high- and low-expression groups, and the associations of the HIF1A-AS1 serum level with clinicopathological features and prognosis were analyzed. Serum level of HIF1A-AS1 was significantly increased from CRC patients as compared to those of health controls (P< 0.05). ROC curve analysis revealed a relative high diagnostic performance of HIF1A-AS1 to distinguish CRC from health controls, with the area under the curves (AUC) of 0.960 (95% CI: 0.940 ∼ 0.980; P< 0.001). Kaplan-Meier analysis showed that differentiation degree, tumor size, TNM stage, T stage, N stage, M stage and serum level of HIF1A-AS1 were all linked to CRC prognosis (All P< 0.05). Compared to CRC patients with low HIF1A-AS1 expression, high expression of patients were associated with a shorter 5-year-survival rate (P< 0.001). Multivariate Cox regression analysis revealed that lower differentiation degree, tumor > 5 cm and higher expression of HIF1A-AS1 were independent risk factors affecting the survival rate of patients with CRC (P< 0.05). Our results illustrated that elevated serum HIF1AAS1 could be clinically functioned as a potential biomarker for CRC diagnoses and prognosis.
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Affiliation(s)
- Wanjun Gong
- Department of Gastrointestinal Surgery, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443000, Hubei, China
| | - Ming Tian
- Department of Hematology, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443000, Hubei, China
| | - Honggen Qiu
- Department of Gastrointestinal Surgery, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443000, Hubei, China
| | - Zhenhua Yang
- Department of Gastrointestinal Surgery, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People's Hospital, Yichang 443000, Hubei, China
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Battaglia P, Baritono E, Remo A, Vendraminelli R, Conti A. KRAS Mutations and M2PK Upregulation in Stool Samples from Individuals with Positive Fecal Occult Blood Tests Screened for Colorectal Cancer. TUMORI JOURNAL 2018; 100:122-7. [DOI: 10.1177/030089161410000202] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background Screening for colorectal cancer (CRC) requires non-invasive methods of high diagnostic sensitivity and specificity. We evaluated the measurement of genetic and protein biomarkers of CRC in stool samples with the aim of testing their clinical utility in a CRC screening program. Patients and Methods Individuals aged 53–75 years who were at risk of CRC and immunochemical fecal occult blood test (iFOBT) positive were invited to submit stool samples for molecular testing prior to colonoscopy. KRAS codon 12 Gly→Asp, Gly, Val, and codon 13 Gly→Cys gene mutations were tested using an in-house real-time ARMS PCR method. M2PK levels in stool samples were measured utilizing a commercial ELISA kit. Results At colonoscopy, 7.6% of patients were found to have CRC, 50% had adenomas, 10.6% had hyperplastic polyps, 20.2% had diverticulosis and hemorrhoids, and 11.6% had normal mucosa. The best sensitivity for CRC (50%) was found in those cases where M2PK and KRAS abnormalities coexisted. M2PK showed a detection rate of 40.3% for adenomas but the combination of M2PK and KRAS abnormalities was found in only 5.7% of adenomas (P <0.01). iFOBT was false positive in 31.8% of cases in which colonoscopy excluded neoplastic lesions, while the coexistence of molecular and enzymatic abnormalities was more specific with false positive rates between 8.3% and 9.0% (P <0.05). Conclusion Our molecular screening approach demonstrates that detection of cancer-associated biomarkers measured in iFOBT-positive stool samples could help separate true from false positives in a FOBT-based screening process. M2PK showed particular promise for the detection of CRC and adenomas.
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Affiliation(s)
- Paolo Battaglia
- Department of Laboratory Medicine, Mater Salutis Hospital, Legnago (Verona), Italy
| | - Elisabetta Baritono
- Department of Laboratory Medicine, Mater Salutis Hospital, Legnago (Verona), Italy
| | - Andrea Remo
- Department of Clinical Pathology, Mater Salutis Hospital, Legnago (Verona), Italy
| | | | - Antonio Conti
- Department of Laboratory Medicine, Mater Salutis Hospital, Legnago (Verona), Italy
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Lee CL, Huang CJ, Yang SH, Chang CC, Huang CC, Chien CC, Yang RN. Discovery of genes from feces correlated with colorectal cancer progression. Oncol Lett 2016; 12:3378-3384. [PMID: 27900008 DOI: 10.3892/ol.2016.5069] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Accepted: 07/20/2016] [Indexed: 12/17/2022] Open
Abstract
Colorectal cancer (CRC) is considered to develop slowly via a progressive accumulation of genetic mutations. Markers of CRC may serve to provide the basis for decision-making, and may assist in cancer prevention, detection and prognostic prediction. DNA and messenger (m)RNA molecules that are present in human feces faithfully represent CRC manifestations. In the present study, exogenous mouse cells verified the feasibility of total fecal RNA as a marker of CRC. Furthermore, five significant genes encoding solute carrier family 15, member 4 (SLC15A4), cluster of differentiation (CD)44, 3-oxoacid CoA-transferase 1 (OXCT1), placenta-specific 8 (PLAC8) and growth arrest-specific 2 (GAS2), which are differentially expressed in the feces of CRC patients, were verified in different CRC cell lines using quantitative polymerase chain reaction. The present study demonstrated that the mRNA level of SLC15A4 was increased in the majority of CRC cell lines evaluated (SW1116, LS123, Caco-2 and T84). An increased level of CD44 mRNA was only detected in an early-stage CRC cell line, SW1116, whereas OXCT1 was expressed at higher levels in the metastatic CRC cell line CC-M3. In addition, two genes, PLAC8 and GAS2, were highly expressed in the recurrent CRC cell line SW620. Genes identified in the feces of CRC patients differed according to their clinical characteristics, and this differential expression was also detected in the corresponding CRC cell lines. In conclusion, feces represent a good marker of CRC and can be interpreted through the appropriate CRC cell lines.
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Affiliation(s)
- Chia-Long Lee
- School of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.; Department of Internal Medicine, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.; School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C
| | - Chi-Jung Huang
- Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.; Department of Biochemistry, National Defense Medical Center, Taipei 11490, Taiwan, R.O.C.; School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C
| | - Shung-Haur Yang
- Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan, R.O.C.; School of Medicine, National Yang Ming University, Taipei 11221, Taiwan, R.O.C
| | - Chun-Chao Chang
- School of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.; Department of Internal Medicine, Division of Gastroenterology and Hepatology, Taipei Medical University Hospital, Taipei 11031, Taiwan, R.O.C
| | - Chi-Cheng Huang
- School of Medicine, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.; School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan, R.O.C.; Department of General Surgery, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C
| | - Chih-Cheng Chien
- Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.; School of Medicine, Fu Jen Catholic University, New Taipei 24205, Taiwan, R.O.C.; Department of Anesthesiology, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C
| | - Ruey-Neng Yang
- Department of Nursing, Ching Kuo Institute of Management and Health, Keelung 20301, Taiwan, R.O.C.; Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei 22174, Taiwan, R.O.C
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Vatandoost N, Ghanbari J, Mojaver M, Avan A, Ghayour-Mobarhan M, Nedaeinia R, Salehi R. Early detection of colorectal cancer: from conventional methods to novel biomarkers. J Cancer Res Clin Oncol 2016; 142:341-51. [PMID: 25687380 DOI: 10.1007/s00432-015-1928-z] [Citation(s) in RCA: 85] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 01/23/2015] [Indexed: 02/06/2023]
Abstract
PURPOSE Colorectal cancer (CRC) is one of the major health problems worldwide and is often diagnosed at late stage. There is growing body of evidence in early detection of this disease with novel screening modalities to reduce compliance and increase specificity of available methods. The aim of current review is to give an overview on currently available screening methods (e.g., fecal occult blood testing (FOBT), flexible sigmoidoscopy, and colonoscopy), with their own merits and disadvantages, and new genetic/epigenetic/protein markers, as novel screening modalities. RESULT There are several serum and fecal biomarkers that can predict CRC and polyps. Overall sensitivities for detection by fecal DNA markers ranged from 53 to 87%, while a panel of serum protein markers provides a sensitivity/specificity up to 85% for CRC. In particular, DNA methylation markers (e.g., SEPT9, SFRP2, and ALX4), circulating microRNAs (e.g., microRNA21), SNPs in microRNAs binding site (e.g., rs4596 located within a target region of the predicted miR-518a-5p and miR-527), protein markers (e.g., carcinoembryonic antigen, N-methyltransferase), or microsatellites instability in tumors with deficient mismatch repair of some genes are among the most interesting and promising biomarkers. CONCLUSION Increasing evidence supports the use of combined fecal and serum biomarkers with sigmoidoscopy and colonoscopy screening in order to maximize the benefits and reduce the number of false-positive tests and patients undergoing invasive methods, which in turn could overcome the limitations of the current screening methods for early detection of CRC and adenomas.
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Affiliation(s)
- Nasimeh Vatandoost
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Jahanafrooz Ghanbari
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mahboobeh Mojaver
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amir Avan
- Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Nedaeinia
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Rasoul Salehi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
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Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousová M, Holubec L, Sturgeon C. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. Int J Cancer 2014; 134:2513-22. [PMID: 23852704 PMCID: PMC4217376 DOI: 10.1002/ijc.28384] [Citation(s) in RCA: 245] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Accepted: 06/25/2013] [Indexed: 02/06/2023]
Abstract
Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.
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Affiliation(s)
- MJ Duffy
- Clinical Research Center, St Vincent’s University Hospital, Dublin 4 and UCD School of Medicine and Medical Science, Conway Institute, University College DublinDublin, Ireland
| | - R Lamerz
- Medical Department II, Klinikum Grosshadern, Med. Klinik IIMunich, Germany
| | - C Haglund
- Department of Surgery, Helsinki University Central HospitalHelsinki, Finland
| | - A Nicolini
- Department of Oncology, University of PisaPisa, Italy
| | - M Kalousová
- Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in PraguePrague, Czech Republic
| | - L Holubec
- Department of Oncology and Radiotherapy, University Hospital of PilsenPilsen, Czech Republic
| | - C Sturgeon
- Department of Clinical Biochemistry, Royal Infirmary of EdinburghEdinburgh, United Kingdom
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Zavoral M, Suchanek S, Majek O, Fric P, Minarikova P, Minarik M, Seifert B, Dusek L. Colorectal cancer screening: 20 years of development and recent progress. World J Gastroenterol 2014; 20:3825-3834. [PMID: 24744575 PMCID: PMC3983439 DOI: 10.3748/wjg.v20.i14.3825] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 11/22/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the second most common cancer in Europe and its incidence is steadily increasing. This trend could be reversed through timely secondary prevention (screening). In the last twenty years, CRC screening programs across Europe have experienced considerable improvements (fecal occult blood testing; transition from opportunistic to population based program settings). The Czech Republic is a typical example of a country with a long history of nationwide CRC screening programs in the face of very high CRC incidence and mortality rates. Each year, approximately 8000 people are diagnosed with CRC and some 4000 die from this malignancy. Twenty years ago, the first pilot studies on CRC screening led to the introduction of the opportunistic Czech National Colorectal Cancer Screening Program in 2000. Originally, this program was based on the guaiac fecal occult blood test (FOBT) offered by general practitioners, followed by colonoscopy in cases of FOBT positivity. The program has continuously evolved, namely with the implementation of immunochemical FOBTs and screening colonoscopy, as well as the involvement of gynecologists. Since the establishment of the Czech CRC Screening Registry in 2006, 2405850 FOBTs have been performed and 104565 preventive colonoscopies recorded within the screening program. The overall program expanded to cover 25.0% of the target population by 2011. However, stagnation in the annual number of performed FOBTs lately has led to switching to the option of a population-based program with personal invitation, which is currently being prepared.
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Brenner H, Hoffmeister M, Birkner B, Stock C. Diagnostic performance of guaiac-based fecal occult blood test in routine screening: state-wide analysis from Bavaria, Germany. Am J Gastroenterol 2014; 109:427-35. [PMID: 24343548 DOI: 10.1038/ajg.2013.424] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2013] [Accepted: 11/10/2013] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Randomized trials have shown that annual or biannual screening by guaiac-based fecal occult blood tests (gFOBTs) reduces colorectal cancer (CRC) mortality. Few clinical studies have evaluated diagnostic performance of gFOBT through validation by colonoscopy in all participants. We aimed for a comprehensive evaluation of diagnostic performance of gFOBT by age and sex under routine screening conditions. METHODS Our analysis is based on 20,884 colonoscopies following up a positive gFOBT and 182,956 primary screening colonoscopies documented in a state-wide quality assurance program in Bavaria, Germany, in 2007-2009. Positive likelihood ratios (LR+), which represent an integrative measure of diagnostic performance, were derived, by age groups (55-59, 60-64, 65-69, 70-74 years) and sex, from a joint and comparative analysis of prevalences of colorectal neoplasms in both groups. RESULTS Overall LR+ (95% confidence intervals) were 1.11 (1.06-1.15), 1.80 (1.72-1.88), and 5.04 (4.64-5.47) for non-advanced adenoma, advanced adenoma, and cancer, respectively. Assuming a specificity of gFOBT of 95.2%, as recently observed in a German study among 2,235 participants of screening colonoscopy, these LR+ would translate to sensitivities of 5.3%, 8.6%, and 24.2% for the three outcomes, respectively. Diagnostic performance was similarly poor among women and men and across age groups. CONCLUSIONS The performance of gFOBT under routine screening conditions is even worse than previously estimated from clinical studies. In routine screening application, gFOBTs are expected to miss more than 9 out of 10 advanced adenomas and 3 out of 4 cancers. These results underline the need and the potential for better noninvasive CRC screening tests.
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Affiliation(s)
- Hermann Brenner
- 1] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany [2] German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Berndt Birkner
- 1] Gastroenterology Practice, Munich, Germany [2] Bavarian Association of Statutory Health Insurance Physicians, Munich, Germany
| | - Christian Stock
- 1] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany [2] Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
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Liao CS, Lin YM, Chang HC, Chen YH, Chong LW, Chen CH, Lin YS, Yang KC, Shih CH. Application of quantitative estimates of fecal hemoglobin concentration for risk prediction of colorectal neoplasia. World J Gastroenterol 2013; 19:8366-8372. [PMID: 24363529 PMCID: PMC3857461 DOI: 10.3748/wjg.v19.i45.8366] [Citation(s) in RCA: 17] [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: 06/30/2013] [Revised: 08/15/2013] [Accepted: 08/29/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the role of the fecal immunochemical test (FIT), used to evaluate fecal hemoglobin concentration, in the prediction of histological grade and risk of colorectal tumors.
METHODS: We enrolled 17881 individuals who attended the two-step colorectal cancer screening program in a single hospital between January 2010 and October 2011. Colonoscopy was recommended to the participants with an FIT of ≥ 12 ngHb/mL buffer. We classified colorectal lesions as cancer (C), advanced adenoma (AA), adenoma (A), and others (O) by their colonoscopic and histological findings. Multiple linear regression analysis adjusted for age and gender was used to determine the association between the FIT results and colorectal tumor grade. The risk of adenomatous neoplasia was estimated by calculating the positive predictive values for different FIT concentrations.
RESULTS: The positive rate of the FIT was 10.9% (1948/17881). The attendance rate for colonoscopy was 63.1% (1229/1948). The number of false positive results was 23. Of these 1229 cases, the numbers of O, A, AA, and C were 759, 221, 201, and 48, respectively. Regression analysis revealed a positive association between histological grade and FIT concentration (β = 0.088, P < 0.01). A significant log-linear relationship was found between the concentration and positive predictive value of the FIT for predicting colorectal tumors (R2 > 0.95, P < 0.001).
CONCLUSION: Higher FIT concentrations are associated with more advanced histological grades. Risk prediction for colorectal neoplasia based on individual FIT concentrations is significant and may help to improve the performance of screening programs.
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Porzsolt F, Thomaz TG, Constâncio TI, Silva-Júnior AGD, Nóbrega ACLD. The risks of information in health care: do we need a new decision aid? Clinics (Sao Paulo) 2013; 68:1177-9. [PMID: 24141831 PMCID: PMC3782712 DOI: 10.6061/clinics/2013(09)01] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Affiliation(s)
- Franz Porzsolt
- Hospital for General and Visceral Surgery, University Hospital Ulm, Ulm, Germany
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Kocna P, Vanickova Z, Zima T. Laboratory screening markers in gastroenterology - state of the art. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013; 157:91-7. [PMID: 23681305 DOI: 10.5507/bp.2013.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2012] [Accepted: 04/10/2013] [Indexed: 11/23/2022] Open
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Brenner H, Tao S. Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy. Eur J Cancer 2013; 49:3049-54. [PMID: 23706981 DOI: 10.1016/j.ejca.2013.04.023] [Citation(s) in RCA: 187] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 04/22/2013] [Accepted: 04/26/2013] [Indexed: 02/06/2023]
Abstract
There is increasing evidence that faecal immunochemical tests (FITs) for haemoglobin offer a number of advantages over traditional guaiac based faecal occult blood tests (gFOBTs). However, evidence on diagnostic performance from direct comparisons with colonoscopy findings in all participants in the average risk population is still sparse. We aimed for a head-to-head comparison of three quantitative FITs with a gFOBT among participants of the German screening colonoscopy programme. Pre-colonoscopy stool samples and colonoscopy reports were obtained from 2235 participants of screening colonoscopy in 2005-2009. To enhance comparability of diagnostic performance of the various tests, we assessed sensitivity, specificity, predictive values and likelihood ratios of FITs after adjusting the FIT cut-off haemoglobin (Hb) concentrations in such a way that FIT positivity rates equalled the positivity rate of the gFOBT. Colorectal cancer, advanced adenomas and other adenomas were found in 15 (0.7%), 207 (9.3%) and 398 (17.8%) participants. The gFOBT was positive in 111 (5.0%) participants, with sensitivities (specificities) for detecting colorectal cancer, any advanced neoplasm or any neoplasm of 33.3% (95.2%), 8.6% (95.4%) and 5.5% (95.2%). At the same positivity rate, all three FITs outperformed the gFOBT in all indicators. In particular, all sensitivities of FITs were approximately two to three times higher at increased levels of specificity. All differences were statistically significant, except for some of the performance indicators for colorectal cancer. In conclusion, FITs can detect much larger proportions of colorectal neoplasms even if their cut-offs are set to levels that ensure equally low positivity rates as gFOBT.
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Affiliation(s)
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld, 69120 Heidelberg, Germany.
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Cai H, Chiorean EG, Chiorean MV, Rex DK, Robb BW, Hahn NM, Liu Z, Loehrer PJ, Harrison ML, Xu Y. Elevated phospholipase A2 activities in plasma samples from multiple cancers. PLoS One 2013; 8:e57081. [PMID: 23451150 PMCID: PMC3579817 DOI: 10.1371/journal.pone.0057081] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2012] [Accepted: 01/17/2013] [Indexed: 12/03/2022] Open
Abstract
Only in recent years have phospholipase A2 enzymes (PLA2s) emerged as cancer targets. In this work, we report the first detection of elevated PLA2 activities in plasma from patients with colorectal, lung, pancreatic, and bladder cancers as compared to healthy controls. Independent sets of clinical plasma samples were obtained from two different sites. The first set was from patients with colorectal cancer (CRC; n = 38) and healthy controls (n = 77). The second set was from patients with lung (n = 95), bladder (n = 31), or pancreatic cancers (n = 38), and healthy controls (n = 79). PLA2 activities were analyzed by a validated quantitative fluorescent assay method and subtype PLA2 activities were defined in the presence of selective inhibitors. The natural PLA2 activity, as well as each subtype of PLA2 activity was elevated in each cancer group as compared to healthy controls. PLA2 activities were increased in late stage vs. early stage cases in CRC. PLA2 activities were not influenced by sex, smoking, alcohol consumption, or body-mass index (BMI). Samples from the two independent sites confirmed the results. Plasma PLA2 activities had approximately 70% specificity and sensitivity to detect cancer. The marker and targeting values of PLA2 activity have been suggested.
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Affiliation(s)
- Hui Cai
- Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
- Department of Thoracic Oncosurgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Elena G. Chiorean
- Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
| | - Michael V. Chiorean
- Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
| | - Douglas K. Rex
- Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
| | - Bruce W. Robb
- Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
| | - Noah M. Hahn
- Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
- Hoosier Oncology Group, Indianapolis, Indiana, United States of America
| | - Ziyue Liu
- Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
| | - Patrick J. Loehrer
- Department of Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
| | - Marietta L. Harrison
- Medicinal Chemistry and Molecular Pharmacology, Oncological Sciences Center, Purdue University Center for Cancer Research, West Lafayette, Indiana, United States of America
| | - Yan Xu
- Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
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