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Liu X, Zhang S, Qiu H, Xie ZQ, Tang WF, Chen Y, Wei X. Investigation of high-mobility group box 1 variants with lymph node status and colorectal cancer risk. World J Gastrointest Oncol 2025; 17:102584. [DOI: 10.4251/wjgo.v17.i4.102584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/31/2024] [Accepted: 01/22/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Accumulating studies indicated that maintain nuclei homeostasis was deemed to the protective factors for the occurrence of cancer. Thus, high-mobility group box 1 (HMGB1) might influence the risk and poorer prognoses of colorectal cancer (CRC).
AIM This study was designed to investigate whether HMGB1 polymorphisms influence the risk and lymph node metastasis (LNM) of CRC.
METHODS Firstly, we designed an investigation with 1003 CRC patients and 1303 cancer-free controls to observe whether HMGB1 rs1412125 T > C and rs1045411 C > T SNPs could influence the risk of cancer. Subsequently, we carried out a correlation-analysis to assess whether these SNPs could alter the risk of LNM.
RESULTS The current investigation suggested a relationship of HMGB1 rs1412125 SNP with the increased susceptibility of CRC. In a subgroup analysis, our findings suggested that this SNP could enhance an occurrence of CRC in ≥ 61 years, non-drinker and body mass index < 24 kg/m2 subgroups. However, we found that there was null association between HMGB1 rs1412125 SNP and LNM, even in different CRC region. These observations were confirmed by calculating the power value (more than 0.8). The association of HMGB1 rs1045411 C > T SNP with CRC risk and LNM was not found in any compare.
CONCLUSION This study highlights a possible association between HMGB1 rs1412125 polymorphism and the increased risk of CRC. In the future, more studies should be conducted to explore HMGB1 rs1412125 polymorphism in relation to CRC development.
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Affiliation(s)
- Xin Liu
- Department of General Surgery, Changzhou Third People’s Hospital, Changzhou 213001, Jiangsu Province, China
| | - Sheng Zhang
- Department of General Surgery, Changzhou Third People’s Hospital, Changzhou 213001, Jiangsu Province, China
| | - Hao Qiu
- Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Zhi-Qiang Xie
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China
| | - Wei-Feng Tang
- Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210000, Jiangsu Province, China
| | - Yu Chen
- Department of Medical Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuqing 350014, Fujian Province, China
| | - Xi Wei
- Department of Pathology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu Province, China
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Peruhova M, Banova-Chakarova S, Miteva DG, Velikova T. Genetic screening of liver cancer: State of the art. World J Hepatol 2024; 16:716-730. [PMID: 38818292 PMCID: PMC11135278 DOI: 10.4254/wjh.v16.i5.716] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 02/14/2024] [Accepted: 04/09/2024] [Indexed: 05/22/2024] Open
Abstract
Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal role in the development and progression of liver cancer. This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer. We discuss the genetic underpinnings of liver cancer, emphasizing the critical role of risk-associated genetic variants, somatic mutations, and epigenetic alterations. We also explore the intricate interplay between environmental factors and genetics, highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy, and advancements in high-throughput sequencing technologies. By synthesizing the latest research findings, we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer, shedding light on their potential to revolutionize early detection, risk assessment, and targeted therapies in the fight against this devastating disease.
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Affiliation(s)
- Milena Peruhova
- Department of Gastroenterology, University Hospital "Heart and Brain", Burgas 8000, Bulgaria
| | - Sonya Banova-Chakarova
- Department of Gastroenterology, University Hospital "Heart and Brain", Burgas 8000, Bulgaria.
| | - Dimitrina Georgieva Miteva
- Department of Genetics, Faculty of Biology, Sofia University" St. Kliment Ohridski, Sofia 1164, Bulgaria
| | - Tsvetelina Velikova
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
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3
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Ferreira B, Heredia A, Serpa J. An integrative view on glucagon function and putative role in the progression of pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC). Mol Cell Endocrinol 2023; 578:112063. [PMID: 37678603 DOI: 10.1016/j.mce.2023.112063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 08/16/2023] [Accepted: 09/02/2023] [Indexed: 09/09/2023]
Abstract
Cancer metabolism research area evolved greatly, however, is still unknown the impact of systemic metabolism control and diet on cancer. It makes sense that systemic regulators of metabolism can act directly on cancer cells and activate signalling, prompting metabolic remodelling needed to sustain cancer cell survival, tumour growth and disease progression. In the present review, we describe the main glucagon functions in the control of glycaemia and of metabolic pathways overall. Furthermore, an integrative view on how glucagon and related signalling pathways can contribute for pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC) progression, since pancreas and liver are the major organs exposed to higher levels of glucagon, pancreas as a producer and liver as a scavenger. The main objective is to bring to discussion some glucagon-dependent mechanisms by presenting an integrative view on microenvironmental and systemic aspects in pNETs and HCC biology.
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Affiliation(s)
- Bárbara Ferreira
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal; Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023, Lisboa, Portugal
| | - Adrián Heredia
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal; Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023, Lisboa, Portugal; Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz MB, 1649-028, Lisboa, Portugal
| | - Jacinta Serpa
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal; Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023, Lisboa, Portugal.
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Bodard S, Liu Y, Guinebert S, Yousra K, Asselah T. Prognostic value of genotyping in hepatocellular carcinoma: A systematic review. J Viral Hepat 2023; 30:582-587. [PMID: 36922710 DOI: 10.1111/jvh.13833] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 02/20/2023] [Accepted: 03/11/2023] [Indexed: 03/18/2023]
Abstract
Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death. Advances in sequencing technology are opening genomics to widespread application for diagnosis and research. The poor prognosis of advanced HCC warrants a personalized approach. The objective was to assess the value of genotyping for risk stratification and prognostication of HCC. We performed a systematic review of manuscripts published on MEDLINE from 1 January 2009 to 1 January 2022, addressing the value of genotyping for HCC risk stratification and prognostication. Publication information for each has been collected using a standardized data extraction form. Twenty-five articles were analysed. This study showed that various genomics approaches (i.e., NGS, SNP, CASP or polymorphisms in circadian genes' association) provided predictive and prognostic information, such as disease control rate, median progression-free survival, and shorter median overall survival. Genotyping, which advances in understanding the molecular origin, could be a solution to predict prognosis or treatment response in patients with HCC.
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Affiliation(s)
- Sylvain Bodard
- AP-HP-centre, Service d'Imagerie Adulte, Hôpital Necker Enfants Malades, Paris, F-75015, France
- Université de Paris Cité, Paris, F-75006, France
- Sorbonne Université, CNRS UMR, INSERM, Laboratoire d'Imagerie Biomédicale (LIB), Paris, F-75006, France
| | - Yan Liu
- Faculty of Life Science and Medicine, King's College London, London, UK
- Median Technologies, 1800 Route des Crêtes, Valbonne, F-06560, France
| | - Sylvain Guinebert
- AP-HP-centre, Service d'Imagerie Adulte, Hôpital Necker Enfants Malades, Paris, F-75015, France
- Université de Paris Cité, Paris, F-75006, France
| | | | - Tarik Asselah
- Université de Paris Cité, Paris, F-75006, France
- APHP.Nord, Service d'hépatologie, INSERM, Hôpital Beaujon, Clichy, F-92110, France
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Xia Q, Tao P, Xu J. Association of Polymorphism rs1045411 in the HMGB1 Gene with Cancer Risk: Evidence from a Meta-analysis. Int J Med Sci 2021; 18:1348-1355. [PMID: 33628090 PMCID: PMC7893572 DOI: 10.7150/ijms.52181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 01/04/2021] [Indexed: 11/19/2022] Open
Abstract
The high-mobility group box protein 1 (HMGB1) rs1045411 polymorphism has been demonstrated to be associated with cancer risk in some studies. However, the results regarding this topic are inconsistent. A meta-analysis was applied to elucidate the association between the HMGB1 rs1045411 polymorphism and cancer risk. Ten relevant studies were subjected to our analysis, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. In total, of 3,918 cases and 5,296 controls were included in this study. The pooled ORs were calculated using a random-effects or fixed-effects model according to the heterogeneity. The pooled results revealed that TT genotype was significantly related to increased cancer risk in the comparisons of TT vs. CC+TC (OR=1.35; 95% CI: 1.09-1.67; p=0.005). Though no statistical significance was achieved between HMGB1 rs1045411 polymorphism and cancer risk in other four genetic models (T vs. C: OR=1.08, 95% CI 0.90-1.30; TC vs. CC: OR=1.01, 95% CI 0.82-1.24; CC vs. TC+TT: OR=0.95, 95% CI 0.77-1.18; TT vs. CC: OR=1.42; 95% CI 0.98-2.05), a trend of increased risk could be drawn. In the subgroup analysis by type of malignancy and ethnicity, no obvious difference was found in the tumour risk regarding the HMGB1 rs1045411 polymorphism amongst the cancer types except for breast cancer (OR=1.94; 95% CI: 1.05-3.59; p=0.03) and hepatocellular carcinoma (OR=1.82; 95% CI: 1.15-2.88; p=0.01), while rs1045411 polymorphism was positively associated with risks of cancer amongst Hans (OR=1.37; 95% CI: 1.11-1.69; p=0.004) rather than Caucasians (OR=0.89; 95% CI: 0.26-3.02; p=0.01). These results suggest that the HMGB1 rs1045411 polymorphism might be associated with increased cancer risk.
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Affiliation(s)
- Quansong Xia
- Department of Clinical Laboratory, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China
| | - Pengzuo Tao
- Department of Clinical Laboratory, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China
| | - Juan Xu
- Department of Internal Medicine, The People's Hospital of Guandu District, Kunming 650200, China
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Chou YE, Yang PJ, Lin CY, Chen YY, Chiang WL, Lin PX, Huang ZY, Huang M, Ho YC, Yang SF. The Impact of HMGB1 Polymorphisms on Prostate Cancer Progression and Clinicopathological Characteristics. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17197247. [PMID: 33023053 PMCID: PMC7579148 DOI: 10.3390/ijerph17197247] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 09/24/2020] [Accepted: 10/01/2020] [Indexed: 02/06/2023]
Abstract
Prostate cancer is one of the major cancers of the genitourinary tract. High-mobility group box 1 (HMGB1) was suggested as a promising therapeutic target for prostate cancer. In this study, we aim to elucidate the associations of HMGB1 single nucleotide polymorphisms (SNPs) with prostate cancer susceptibility and clinicopathological characteristics. The HMGB1 SNPs rs1412125, rs2249825, rs1045411, and rs1360485 in 579 prostate cancer patients and 579 cancer-free controls were analyzed with real-time polymerase chain reactions (real-time PCR). All of the data were evaluated with SAS statistical software. Our results showed that the HMGB1 rs1045411 T allele genotype was significantly associated with advanced pathologic T stage (odds ratio (OR) = 1.433, 95% confidence interval (CI) = 1.021–2.012; p = 0.037) and pathologic N1 stage (OR = 2.091, 95% CI = 1.160–3.767; p = 0.012), and the rs1360485 polymorphic CT + TT genotype was associated with pathologic Gleason grade group (4 + 5) (OR = 1.583, 95% CI = 1.017–2.462; p = 0.041), pathologic T stage (3 + 4) (OR = 1.482, 95% CI = 1.061–2.070; p = 0.021), and pathologic N1 stage (OR = 2.131, 95% CI = 1.178–3.852; p = 0.011) compared with their wild-type carriers. In conclusion, our results revealed that the HMGB1 SNPs were associated with the clinical status of prostate cancer. The HMGB1 SNPs may have the potential to predict prostate cancer disease progression.
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Affiliation(s)
- Ying-Erh Chou
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; (Y.-E.C.); (P.-J.Y.)
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan;
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Po-Jen Yang
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; (Y.-E.C.); (P.-J.Y.)
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan;
- Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan
| | - Chia-Yen Lin
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan;
- Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 407, Taiwan
| | - Yen-Yu Chen
- School of Medical Applied Chemistry, Chung Shan Medical University, Taichung 402, Taiwan;
| | - Whei-Ling Chiang
- School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan; (W.-L.C.); (P.-X.L.); (Z.-Y.H.)
| | - Pei-Xuan Lin
- School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan; (W.-L.C.); (P.-X.L.); (Z.-Y.H.)
| | - Zih-Yun Huang
- School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan; (W.-L.C.); (P.-X.L.); (Z.-Y.H.)
| | - Matthew Huang
- White Oaks Secondary School, Oakville, ON L6H 1Z5, Canada;
| | - Yung-Chuan Ho
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- School of Medical Applied Chemistry, Chung Shan Medical University, Taichung 402, Taiwan;
- Correspondence: (Y.-C.H.); (S.-F.Y.)
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan;
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- Correspondence: (Y.-C.H.); (S.-F.Y.)
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Li L, Liu Y, Li X, Qiu C. Insights into the genetic basis of HMGB1 in atrial fibrillation in a Chinese Han population. Cardiovasc Diagn Ther 2020; 10:388-395. [PMID: 32695619 DOI: 10.21037/cdt.2019.12.07] [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: 12/27/2022]
Abstract
Background Atrial fibrillation (AF) is the most common cardiac arrhythmia. High mobility group box 1 (HMGB1) has been demonstrated to be involved in AF, but the genetic relationship between them is not clear yet. Here, we investigated the genetic association between functional variants in HMGB1 and AF in a Chinese Han population. Methods Two common variants (the promoter one rs1045411T/C and the 3'UTR one rs1412125C/T) in HMGB1 were selected and genotyped in 576 AF patients and 869 control subjects. Traditional risk factors, such as age, gender, the history of smoking, hypertension and diabetes mellitus, were adjusted as covariates using a logistic regression analysis (SPSS, v.21.0). The haplotypic analysis was performed using SPSS (v.21.0, Inc., Chicago, IL, USA). Results Under the allelic association analysis, neither rs1045411T/C nor rs1412125C/T was associated with AF with all P values >0.05; under the genotypic association analysis, the 3'UTR variant rs1045411T showed a marginally significant association with AF under the recessive model (Padj=0.056, OR =0.42; 95% CI: 0.17-1.02). When divided the studied population by gender, we still found no significant association results between the selected variants and AF with P values more than 0.05; however, when divided the population into subgroups by the age onset of AF, we found that the 3'UTR variant rs1045411T was significantly associated with AF in the late-onset subgroup (Padj=0.009, OR =11.1; 95% CI: 1.82-50.0). Conclusions The 3'UTR variant rs1045411T/C of HMGB1 might influence the risk of late-onset AF in the Chinese Han population, which provides an important target factor for the prevention and treatment study of AF.
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Affiliation(s)
- Li Li
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.,Department of Emergency Internal Medicine, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, China
| | - Yang Liu
- Department of Emergency Internal Medicine, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, China
| | - Xinxin Li
- Department of Emergency Internal Medicine, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, China
| | - Chunguang Qiu
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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Zhou YK, Li XP, Yin JY, Zou T, Wang Z, Wang Y, Cao L, Chen J, Liu ZQ. Association of variations in platinum resistance-related genes and prognosis in lung cancer patients. J Cancer 2020; 11:4343-4351. [PMID: 32489453 PMCID: PMC7255368 DOI: 10.7150/jca.44410] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/29/2020] [Indexed: 01/25/2023] Open
Abstract
Purpose: We aimed to investigate the association of single-nucleotide polymorphisms (SNPs) in HMGB1, REV3L, and NFE2L2 with prognosis in lung cancer patients with platinum-based chemotherapy. Methods: We have recruited 348 lung cancer patients treated with platinum. Log-rank test and Cox regression analysis were used to assess overall survival (OS) and progression-free survival (PFS) among SNP genotypes. Results: The results revealed that patients carrying TC or CC genotype in REV3L rs462779 (HR=0.67, 95% CI=0.51-0.90, P=0.007) and AG or GG genotype in HMGB1 rs1045411 (HR=0.61, 95% CI=0.38-0.99, P=0.046) had a better overall survival. Additionally, carrying TC or TT genotype in rs462779 had a lower risk (OR=0.38, 95% CI=0.17-0.89, P=0.025) of lymph node metastasis, carrying AG or AA genotype in rs1045411 was significantly related to early T stage (OR=0.47, 95% CI=0.29-0.76, P=0.002). In stratified analysis, patients with TC or CC genotype in rs462779 were significantly associated with overall survival in male patients, never-smokers, patients with younger age (≤56), no family history of cancer, adenocarcinoma, advanced stage (stage III or IV), or ECOG PS 0-1. While patients with AG or GG genotype in rs1045411 were significantly associated with overall survival in patients with advanced stage (stage III or IV) or ECOG PS 0-1. Conclusion: Our results indicate that the TC or CC genotype in rs462779 and AG or GG genotype in rs1045411 are contributed to better overall survival. The REV3L rs462779 and HMGB1 rs1045411 may serve as prognosis markers in lung cancer patients with platinum-based chemotherapy.
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Affiliation(s)
- Yuan-Kang Zhou
- Department of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorder, Xiangya Hospital, Central South University, Changsha 410008, China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China
| | - Xiang-Ping Li
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Ji-Ye Yin
- Department of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorder, Xiangya Hospital, Central South University, Changsha 410008, China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China
| | - Ting Zou
- Department of National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Zhan Wang
- Department of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, 410013, China
| | - Ying Wang
- Department of the Central Laboratory, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, 410013, China
| | - Lei Cao
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Juan Chen
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- ✉ Corresponding authors: Zhao-Qian Liu, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008; China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078; China. Tel: +86 731 89753845, Fax: +86 731 82354476, E-mail: or Juan Chen, Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008; China. E-mail:
| | - Zhao-Qian Liu
- Department of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorder, Xiangya Hospital, Central South University, Changsha 410008, China
- Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China
- ✉ Corresponding authors: Zhao-Qian Liu, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008; China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078; China. Tel: +86 731 89753845, Fax: +86 731 82354476, E-mail: or Juan Chen, Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008; China. E-mail:
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Hu W, Chien SY, Ying P, Liu PI, Su CM, Tang CH. Impact of CCL4 gene polymorphisms upon the progression of lung cancer in a Han Chinese cohort. Medicine (Baltimore) 2020; 99:e18906. [PMID: 32011520 PMCID: PMC7220213 DOI: 10.1097/md.0000000000018906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Lung cancer is the most common malignancy in China and has a low survival rate amongst Han Chinese. The high mortality is largely attributed to late-stage diagnosis, when treatment is largely ineffective. Identification of genetic variants could potentially assist with earlier diagnosis and thus more effective treatment. Chemokine (C-C motif) ligand 4 (CCL4) plays a critical role as a chemoattractant in tumor development, metastasis and angiogenesis. In this study, we explored three CCL4 single nucleotide polymorphisms (SNPs) (rs1634507, rs1719153, and rs10491121) in 538 patients with lung cancer and 370 healthy, cancer-free controls. Carriers of the GT + TT heterozygote of rs1634507 had a lower risk of lung cancer than wild-type (GG) carriers, while the presence of the AG + GG heterozygote at rs10491121 was associated with a higher risk of lung cancer compared with having the AA genotype. The G/A/G and T/A/A CCL4 haplotypes significantly reduced and increased the risks for lung cancer, respectively. Our study is the first to document correlations between CCL4 polymorphisms and lung cancer development and progression in people of Han Chinese ethnicity.
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Affiliation(s)
- Weiwei Hu
- Department of Thoracic Surgery, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Szu-Yu Chien
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Pengqing Ying
- Department of Thoracic Surgery, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Po-I Liu
- Graduate Institute of Biomedical Science, China Medical University, Taichung,
- Department of Thoracic Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Chen-Ming Su
- Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Chih-Hsin Tang
- School of Medicine, China Medical University, Taichung, Taiwan
- Graduate Institute of Biomedical Science, China Medical University, Taichung,
- Chinese Medicine Research Center, China Medical University
- Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
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Chhipa AS, Borse SP, Baksi R, Lalotra S, Nivsarkar M. Targeting receptors of advanced glycation end products (RAGE): Preventing diabetes induced cancer and diabetic complications. Pathol Res Pract 2019; 215:152643. [PMID: 31564569 DOI: 10.1016/j.prp.2019.152643] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 08/30/2019] [Accepted: 09/15/2019] [Indexed: 12/13/2022]
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Investigation of ICOS, CD28 and CD80 polymorphisms with the risk of hepatocellular carcinoma: a case-control study in eastern Chinese population. Biosci Rep 2019; 39:BSR20181824. [PMID: 31235485 PMCID: PMC6609557 DOI: 10.1042/bsr20181824] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 06/06/2019] [Accepted: 06/19/2019] [Indexed: 12/12/2022] Open
Abstract
Single nucleotide polymorphisms (SNPs) in immune related gene may influence the susceptibility of cancer. We selected inducible T cell costimulator (ICOS) rs4404254 T>C, rs10932029 T>C, CD28 rs3116496 T>C and CD80 rs7628626 C>A SNPs and assessed the potential relationship of these SNPs with hepatocellular carcinoma (HCC) risk. A total of 584 HCC cases and 923 healthy controls were recruited. And SNPscan™ genotyping assay was used to obtain the genotypes of ICOS, CD28 and CD80 polymorphisms. We found that ICOS rs10932029 T>C polymorphism significantly increased the risk of HCC (additive model: adjusted odds ratio (OR), 1.59; 95% confidence interval (CI), 1.13-2.22; P=0.007; homozygote model: adjusted OR, 1.12; 95% CI, 0.31-4.03; P=0.867; dominant model: adjusted OR, 1.58; 95% CI, 1.14-2.19; P=0.007 and recessive model: adjusted OR, 1.02; 95% CI, 0.28-3.68; P=0.974). However, ICOS rs4404254 T>C, CD28 rs3116496 T>C and CD80 rs7628626 C>A SNPs were not associated with the risk of HCC. To evaluate the effects of ICOS rs10932029 T>C on HCC risk according to different age, gender, chronic hepatitis B virus (HBV) infection, tobacco consumption and drinking status, we carried out a stratification analysis. We found that ICOS rs10932029 T>C polymorphism might increase the risk of HCC in male, ≥53 years, never smoking, never drinking and non-chronic HBV infection subgroups. Our study highlights that ICOS rs10932029 T>C polymorphism may confer the susceptibility to HCC. It may be beneficial to explore the relationship between variants in immune related genes and the development of HCC.
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Wu YL, Chien MH, Chou YE, Chang JH, Liu TC, Tsao TCY, Chou MC, Yang SF. Association of EGFR mutations and HMGB1 genetic polymorphisms in lung adenocarcinoma patients. J Cancer 2019; 10:2907-2914. [PMID: 31281467 PMCID: PMC6590032 DOI: 10.7150/jca.31125] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 04/11/2019] [Indexed: 12/14/2022] Open
Abstract
High-mobility group protein box 1 (HMGB1) is overexpressed and reported to be a prognostic factor in patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutants play an important role in NSCLC progression. The aim of this study was to explore potential associations between genetic polymorphisms of HMGB1 and EGFR mutations in a cohort that included 280 patients with NSCLC, some of whom were smokers and others who never smoked. Four tagged single-nucleotide polymorphisms (SNPs) of HMGB1 were detected by a TaqMan-based real-time polymerase chain reaction (PCR) in patients. We found that after adjusting for other covariates, NSCLC patients who smoked and who respectively had CG, CT, and TC heterozygotes of HMGB1 rs2249825, rs1045411, and rs1360485, were at lower risk of developing mutant EGFR, compared to those patients with wild-type homozygotes. Moreover, significant inverse associations between the CG and CG + GG genotypes of HMGB1 rs2249825 and the EGFR hotspot mutation, an exon 19 in-frame deletion, were also observed among NSCLC patients. Within patients harboring mutant EGFR, HMGB1 rs1360485 C (TC + CC) allele carriers were at higher risk of developing poorly differentiated cancer types (odds ratio=5.493, 95% confidence interval: 1.130~26.696, p=0.019), compared to patients with TT homozygotes. Furthermore, we found that HMGB1 rs1360485 polymorphisms seemed to be related to susceptibility to developing poorly differentiated cancer linked to tobacco consumption in EGFR mutant patients. In conclusion, our results suggested that HMGB1 variants are significantly inversely associated with EGFR mutations among NSCLC patients who smoked. HMGB1 variants and tobacco consumption might contribute to the pathological development of NSCLC.
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Affiliation(s)
- Yi-Liang Wu
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Ming-Hsien Chien
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Ying-Erh Chou
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Jer-Hwa Chang
- Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Tu-Chen Liu
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Chest Medicine, Cheng-Ching General Hospital, Taichung, Taiwan
| | - Thomas Chang-Yao Tsao
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Division of Chest, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Ming-Chih Chou
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
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Song W, Tan H, Wang S, Zhang Y, Ding Y. Association of High Mobility Group Box Protein B1 Gene Polymorphisms with Pneumonia Susceptibility and Severity. Genet Test Mol Biomarkers 2018; 23:3-11. [PMID: 30562142 DOI: 10.1089/gtmb.2018.0174] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVE To investigate the relationship between the high mobility group box protein B1 (HMGB1) single nucleotide polymorphisms (SNPs) rs1412125, rs2249825, and rs1045411 with pneumonia in terms of susceptibility, severity, and inflammatory response. METHODS The genotypes of HMGB1 rs1412125 (-1615T > C), rs2249825 (3814C > G), and rs1045411 (2262C > T) loci in 328 patients with community-acquired pneumonia (CAP) and 317 healthy subjects were analyzed by Sanger sequencing. The expression and secretion of the inflammatory cytokines HMGB1, interleukin (IL)-10, tumor necrosis factor-alpha (TNF-α), and IL-6 were determined after lipopolysaccharide (LPS) stimulation of peripheral whole blood cells. RESULTS The risk of CAP was higher in carriers of the mutant HMGB1 rs1412125 and rs2249825 alleles than those that had the wild type alleles (adjusted odds ratio [OR] = 1.241; 95% confidence interval [CI] = 1.061-1.448; p = 0.007; adjusted OR = 1.225; 95% CI = 1.038-1.427; p = 0.016, respectively). Moreover, the mutation-carrying patients with CAP were more likely to develop severe community-acquired pneumonia (SCAP). There was no correlation between the HMGB1 rs1045411 SNP alleles and CAP or SCAP (p > 0.05). The expression and secretion of the inflammatory cytokines HMGB1, IL-10, TNF-α, and IL-6 was significantly higher in LPS-stimulated peripheral blood among patients with mutations at the rs1412125 and rs2249825 loci compared with those with wild type alleles (p < 0.05). The 30-day mortality rates for CAP patients with mutations at the rs1412125 and rs2249825 loci of HMGB1 were significantly higher than those that had wild type alleles. The mortality rate difference between rs1045411 wild-type CAP patients and mutant was not significant (p = 0.789). CONCLUSION SNPs at the rs1412125 and rs2249825 loci of HMGB1 are associated with pneumonia in terms of susceptibility, severity, and inflammatory response.
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Affiliation(s)
- Weiwei Song
- 1 Department of Critical Care Medicine, Zibo Central Hospital, Zibo, China
| | - Haibo Tan
- 1 Department of Critical Care Medicine, Zibo Central Hospital, Zibo, China
| | - Shifu Wang
- 1 Department of Critical Care Medicine, Zibo Central Hospital, Zibo, China
| | - Yun Zhang
- 1 Department of Critical Care Medicine, Zibo Central Hospital, Zibo, China
| | - Yueping Ding
- 2 Department of Intensive Care Unit, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
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Associations between HMGB1 gene polymorphisms and susceptibility and clinical outcomes in Chinese Han sepsis patients. Gene 2018; 687:23-29. [PMID: 30423384 DOI: 10.1016/j.gene.2018.11.027] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Revised: 10/02/2018] [Accepted: 11/08/2018] [Indexed: 01/27/2023]
Abstract
OBJECTIVES High mobility group box 1 protein (HMGB1) is an important late inflammatory mediator in the body. In recent years, studies have found that it plays an important pathogenic role in various diseases such as sepsis. However, it is unclear whether the genetic variation of the HMGB1 gene is related to the susceptibility to sepsis. This study investigated the relationship between susceptibility and outcome of the HMGB1 gene rs2249825, rs1045411, and rs1360485 single nucleotide polymorphisms (SNPs) in Chinese Han patients with sepsis. METHODS The HMGB1 gene rs2249825, rs1045411, and rs1360485 genotypes were detected by the direct sequencing method in 345 patients with sepsis and 345 healthy controls. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS The HMGB1 gene rs2249825 and rs1045411 site SNPs were associated with sepsis risk, but the rs1360485 site SNP was not associated with sepsis risk. Subjects with the HMGB1 gene rs2249825 and rs1045411 site mutations had higher serum HMGB1 levels, and patients with mutant genotype sepsis had higher APACHE II scores and lower 30-day survival rates. There were no correlations among the rs1360485 site SNP, sepsis risk, and patient 30-day survival. CONCLUSION The HMGB1 gene rs2249825 and rs1045411 site SNPs are associated with susceptibility and outcomes of Chinese Han patients with sepsis. The rs2249825 locus C allele and the rs1045411 locus A allele are high risk factors for sepsis and severity in the Chinese Han population, and are associated with adverse outcomes in patients with sepsis.
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15
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No association between HMGB1 polymorphisms and cancer risk: evidence from a meta-analysis. Biosci Rep 2018; 38:BSR20180658. [PMID: 30049847 PMCID: PMC6123066 DOI: 10.1042/bsr20180658] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 07/05/2018] [Accepted: 07/18/2018] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to determine whether High mobility group box 1 (HMGB1) polymorphism was associated with cancer susceptibility. PubMed, Embase, and ISI Web of Science were extensively searched without language restriction. Data were extracted using a standardized data collection sheet after two reviewers scanned studies independently. The association between HMGB1 polymorphism and cancer risks was indicated as odds ratio (OR) along with its related 95% confidence interval (95%CI). Meta-analysis was conducted via RevMan 5.3 software. A total of ten studies comprising 4530 cases and 5167 controls were included in our study. Meta-analysis revealed no statistical association between rs1045411, rs1360485, rs1412125, or rs2249825 polymorphisms in HMGB1 gene and risk of cancer, either did subgroup analysis of rs1045411 stratified by cancer types and ethnic groups. Our results revealed no statistical association between current four polymorphism loci and cancer risks, suggesting that the attempt of applying HMGB1 variants as a therapeutic target or a prognosis predictor might still require a second thought. However, HMGB1 is deemed to play pleiotropic roles in cancers, we strongly call for large-scale studies with high evidence level to uncover the exact relationship between HMGB1 gene variants and cancer progression.
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A multicenter matched case-control analysis on seven polymorphisms from HMGB1 and RAGE genes in predicting hepatocellular carcinoma risk. Oncotarget 2018; 8:50109-50116. [PMID: 28187002 PMCID: PMC5564833 DOI: 10.18632/oncotarget.15202] [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: 12/22/2016] [Accepted: 01/25/2017] [Indexed: 12/21/2022] Open
Abstract
Based on 540 hepatocellular carcinoma patients and 540 age- and gender-matched controls, we tested the hypothesis that high mobility group protein box1 (HMGB1) and the receptor for advanced glycation end products (RAGE) genes are two potential candidate susceptibility genes for hepatocellular carcinoma in a multicenter hospital-based case-control analysis. The genotypes of seven widely-studied polymorphisms were determined, and their distributions respected the Hardy-Weinberg equilibrium. The mutant alleles of two polymorphisms, rs1045411 in HMGB1 gene and rs2070600 in RAGE gene, had significantly higher frequencies in patients than in controls (P < 0.001), with the power to detect this significance of being over 99.9%. Moreover, the above two polymorphisms increased the risk of developing hepatocellular carcinoma significantly, particularly for rs2070600 under the additive (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.34-2.32; P < 0.001) and dominant (OR = 1.75; 95% CI: 1.23-2.50; P = 0.002) models after adjusting for body mass index, smoking and drinking. Haplotype analysis showed that the T-C-T haplotype (rs1045411-rs2249825-rs1415125) in HMGB1 gene was associated with a 2.47-fold (95% CI: 1.41-4.34; P = 0.002) increased risk of hepatocellular carcinoma compared with the commonest C-C-T haplotype after adjustment. In RAGE gene, the T-T-A-G (rs1800625-rs1800624-rs2070600-rs184003) (adjusted OR; 95% CI; P: 1.75; 1.02-3.03; 0.045) and T-T-A-T (adjusted OR; 95% CI; P: 1.95; 1.01-3.76; 0.048) haplotypes were associated with a marginally increased risk of hepatocellular carcinoma compared with the commonest T-T-G-G haplotype. In summary, we identified two risk-associated polymorphisms (rs1045411 and rs2070600), and more importantly a joint impact of seven polymorphisms from the HMGB1/RAGE axis in susceptibility to hepatocellular carcinoma.
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High-mobility group box 1 protein (HMGB1) gene polymorphisms and cancer susceptibility: A comprehensive meta-analysis. Clin Chim Acta 2018; 483:170-182. [PMID: 29730397 DOI: 10.1016/j.cca.2018.04.042] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 04/30/2018] [Accepted: 04/30/2018] [Indexed: 02/07/2023]
Abstract
AIM The role of HMGB1 polymorphisms in cancer predisposition remains unclear. This meta-analysis was performed assess four HMGB1 polymorphisms (rs1045411, rs2249825, rs1360485 and rs1412125) in cancer risk. METHODS We searched published studies till January 2018 from EMBASE, PubMed, Google scholar, and Cochrane library. Thereafter, the statistical software "R" was used to calculate Pooled Odds Ratios (OR), and 95% confidence intervals (CI) for assessment of association between different HMGB1 polymorphisms and cancer risk. RESULT In this meta-analysis we used eight studies totaling 7017 subjects. HMGB1 rs1045411 polymorphism in recessive model (OR 1.4159, 95% CI 0.9197-2.1798, P = 0.1142) and homozygous model (OR 1.4157, 95% CI 0.8711-2.3006, P = 0.1606) emerged as a risk factor for cancer development. Dominant model in rs2249825 polymorphism (OR: 0.8954) and rs1412125 polymorphism (OR: 0.9029) emerged as protective factors. Statistical significance was not achieved for any genetic model. Begg's test and Egger's test for all analysis suggested no publication bias. CONCLUSION This is the first meta-analysis exploring the association of four HMGB1 polymorphisms with cancer. Although polymorphism rs1045411 emerged as a risk candidate, additional studies are suggested to confirm these findings.
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18
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A six-gene-based prognostic signature for hepatocellular carcinoma overall survival prediction. Life Sci 2018; 203:83-91. [PMID: 29678742 DOI: 10.1016/j.lfs.2018.04.025] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 03/16/2018] [Accepted: 04/16/2018] [Indexed: 01/09/2023]
Abstract
AIMS The purpose of this study was to propose a pipeline to identify prognostic signature for HCC overall survival (OS) prediction based on HCC gene expression datasets from The Cancer Genome Atlas (TCGA). RESULTS Differential expression analysis identified 3573 genes aberrantly expressed (DEGs) in HCC samples. Univariate cox regression analysis obtained 1605 and 1067 HCC OS and relapse free survival (RFS) related genes, which are abbreviated as OS-Gene and RFS-Gene respectively. Besides, there are 55 overlaps among DEGs, OS-Genes and RFS-Genes. Further prioritization of the 55 overlapping genes through Sure Independence Screening (SIS) resulted in 6 genes, including SRL, TTC26, CPSF2, TAF3, C16orf46 and CSN1S1, and the prognostic signature is the weighted combination of their expression values. Kaplan-Meier analysis based on the prognostic score (PS) of every sample indicates higher PS is associated with better HCC OS. Robustness of the prognostic signature was evaluated through another HCC gene expression datasets from the Gene Expression Omnibus (GEO). What's more, univariate and multivariate cox regression analysis indicate significant associations between stage/PS and HCC OS. CONCLUSIONS Our study provides a pipeline for the identification of prognostic signature for HCC OS prediction, which should also be suit for other types of cancers.
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19
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Jiang M, Li X, Quan X, Li X, Zhou B. Single Nucleotide Polymorphisms in HMGB1 Correlate with Lung Cancer Risk in the Northeast Chinese Han Population. Molecules 2018; 23:E832. [PMID: 29617336 PMCID: PMC6017634 DOI: 10.3390/molecules23040832] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 03/26/2018] [Accepted: 04/01/2018] [Indexed: 12/18/2022] Open
Abstract
Lung cancer is the principal cause of cancer-associated deaths. HMGB1 has been reported to be associated with tumorigenesis. This study aimed to investigate the relationship between rs1412125 and rs1360485 polymorphisms in HMGB1 and the risk and survival of lung cancer. 850 cases and 733 controls were included. Logistic regression analysis and survival analysis were performed to investigate the association between SNPs and the risk and survival of lung cancer. Crossover analysis was used to analyze the interaction between SNPs and tobacco exposure. Results indicated that rs1412125 polymorphism was associated with lung cancer risk, especially with the risk of lung adenocarcinoma and small cell lung cancer. Carriers with CT and CC genotypes had a decreased risk of lung cancer (CT + CC vs.TT: adjusted OR = 0.736, p = 0.004). Similar results were obtained in the stratification analysis for non-smokers and female population. For rs1360485 polymorphism, AG and GG genotypes could decrease the risk of lung adenocarcinoma and female lung cancer by 0.771-fold and 0.789-fold. However, no significant interaction between polymorphisms and tobacco exposure or association between SNPs and the survival of lung cancer was observed. This study indicated polymorphisms in HMGB1 may be a novel biomarker for female lung adenocarcinoma risk.
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Affiliation(s)
- Min Jiang
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, China.
- Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, Shenyang 110122, China.
| | - Xuelian Li
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, China.
- Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, Shenyang 110122, China.
| | - Xiaowei Quan
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, China.
- Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, Shenyang 110122, China.
| | - Xiaoying Li
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, China.
- Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, Shenyang 110122, China.
| | - Baosen Zhou
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, China.
- Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, Shenyang 110122, China.
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A functional variant at the miRNA binding site in HMGB1 gene is associated with risk of oral squamous cell carcinoma. Oncotarget 2018; 8:34630-34642. [PMID: 28423715 PMCID: PMC5470997 DOI: 10.18632/oncotarget.16120] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 02/15/2017] [Indexed: 12/12/2022] Open
Abstract
Oral squamous cell carcinoma (OSCC) is a common malignancy that has been causally associated with both hereditary and acquired factors. The high mobility group box 1 (HMGB1) gene plays an important role as a DNA chaperone to help maintain nuclear homeostasis. Altered expression of HMGB1 has been implicated in a wide range of pathological processes, including inflammation and cancer. The present study explores the impact of HMGB1 gene polymorphisms, combined with environmental risks regarding susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms (SNPs) of the HMGB1 gene, rs1412125, rs2249825, rs1045411, and rs1360485, were evaluated in 1,200 normal controls and 772 patients with OSCC. We found an association between the wild-type allele of rs1045411 and genotypes CT and CT/TT (AOR=0.754, 95% CI=0.582-0.978 and AOR=0.778, 95% CI=0.609-0.995, respectively). Additionally, bioinformatics analysis was used to characterize the functional relevance of these variants for the miRNA-505-5p binding site and transcriptional regulation by the HMGB1 3’-UTR and promoter regions. Moreover, in considering behavioral exposure to environmental carcinogens, the presence of the four HMGB1 SNPs, combined with/without betel quid chewing and smoking showed, profoundly synergistic effects on the risk of OSCC. In conclusion, we present a potential clinical relevance for HMGB1 variants in OSCC, as well as associations between HMGB1 polymorphisms, haplotypes and environmental risk factors. The finding may help in development of optimal therapeutic approaches for OSCC patients.
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Hung SC, Wang SS, Li JR, Chen CS, Yang CK, Chiu KY, Cheng CL, Ou YC, Ho HC, Yang SF. Effect of HMGB1 Polymorphisms on Urothelial Cell Carcinoma Susceptibility and Clinicopathological Characteristics. Int J Med Sci 2018; 15:1731-1736. [PMID: 30588197 PMCID: PMC6299401 DOI: 10.7150/ijms.27901] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 10/18/2018] [Indexed: 12/29/2022] Open
Abstract
The high mobility group box 1 gene (HMGB1) plays a prominent role in cancer progression, angiogenesis, invasion, and metastasis. This study explored the effect of HMGB1 polymorphisms on clinicopathological characteristics of urothelial cell carcinoma (UCC). In total, 1293 participants (431 patients with UCC and 862 healthy controls) were recruited. Four single-nucleotide polymorphisms (SNPs) of HMGB1 (rs1412125, rs1360485, rs1045411, and rs2249825) were assessed using TaqMan real-time polymerase chain reaction assay. The results indicated that individuals carrying at least one T allele at rs1045411 had a lower risk of UCC than those with the wild-type allele [adjusted odds ratio = 0.722, 95% confidence interval (CI) = 0.565-0.924]. Furthermore, female patients with UCC carrying at least one T allele at rs1045411 were at a lower invasive tumor stage than those with the wild-type allele [odds ratio (OR) = 0.396, 95% CI = 0.169-0.929], similar to nonsmoking patients (OR = 0.607, 95% CI = 0.374-0.985). In conclusion, this is the first report on correlation between HMGB1 polymorphisms and UCC risk. Individuals carrying at least one T allele at rs1045411 are associated with a lower risk of UCC and a less invasive disease in women and nonsmokers.
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Affiliation(s)
- Sheng-Chun Hung
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Shian-Shiang Wang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.,Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan
| | - Jian-Ri Li
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.,Department of Medicine and Nursing, Hungkuang University, Taichung, Taiwan Taiwan
| | - Chuan-Shu Chen
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chun-Kuang Yang
- Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Kun-Yuan Chiu
- Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.,Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan
| | - Chen-Li Cheng
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yen-Chuan Ou
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.,Department of Urology, Tung's Taichung MetroHarbor Hospital, Taichung, Taiwan
| | - Hao-Chung Ho
- Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
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22
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Huang BF, Tzeng HE, Chen PC, Wang CQ, Su CM, Wang Y, Hu GN, Zhao YM, Wang Q, Tang CH. HMGB1 genetic polymorphisms are biomarkers for the development and progression of breast cancer. Int J Med Sci 2018; 15:580-586. [PMID: 29725248 PMCID: PMC5930459 DOI: 10.7150/ijms.23462] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 03/01/2018] [Indexed: 12/14/2022] Open
Abstract
Breast cancer is a major cause of cancer mortality worldwide. High-mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein found in all mammal eukaryotic cells that participates in tumor progression, migration and metastasis. HMGB1 overexpression has been indicated in breast cancer patients. However, scant information is available regarding the association between HMGB1 single nucleotide polymorphisms (SNPs) and the risk or prognosis of breast cancer. We report on the association between 4 SNPs of the HMGB1 gene (rs1360485, rs1045411, rs2249825 and rs1412125) and breast cancer susceptibility as well as clinical outcomes in 313 patients with breast cancer and in 217 healthy controls. Patients with one G allele in the rs1360485 or rs2249825 domains are likely to progress to T2 tumor and lymph node metastasis. In addition, the presence of one G allele in SNPs rs1360485 or rs2249825 was associated with a higher risk of progressing to T2 tumor and distant metastasis amongst HER2-enriched and triple-negative breast cancer (TNBC) tumors compared with luminal A and luminal B tumors. Furthermore, having one C allele in the rs1412125 domain increased the risk of pathologic grade 3 disease in HER2-enriched and TNBC tumors. Our results indicate that genetic variations in the HMGB1 gene may serve as an important predictor of breast cancer progression and metastasis.
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Affiliation(s)
- Bi-Fei Huang
- Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Huey-En Tzeng
- Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.,Department of Internal Medicine, Division of Hematology and Oncology, Taipei Medical University Hospital, Taipei, Taiwan
| | - Po-Chun Chen
- Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
| | - Chao-Qun Wang
- Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Chen-Ming Su
- Laboratory of Biomedicine, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Yan Wang
- Department of Medical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Gui-Nv Hu
- Department of Surgical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Yong-Ming Zhao
- Department of Surgical Oncology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Qian Wang
- Department of Pathology, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Chih-Hsin Tang
- Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.,Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.,Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
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23
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Wang B, Hsu CJ, Chou CH, Lee HL, Chiang WL, Su CM, Tsai HC, Yang SF, Tang CH. Variations in the AURKA Gene: Biomarkers for the Development and Progression of Hepatocellular Carcinoma. Int J Med Sci 2018; 15:170-175. [PMID: 29333101 PMCID: PMC5765730 DOI: 10.7150/ijms.22513] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 11/15/2017] [Indexed: 12/20/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a liver malignancy and a major cause of cancer mortality worldwide. AURKA (aurora kinase A) is a mitotic serine/threonine kinase that functions as an oncogene and plays a critical role in hepatocarcinogenesis. We report on the association between 4 single nucleotide polymorphisms (SNPs) of the AURKA gene (rs1047972, rs2273535, rs2064836, and rs6024836) and HCC susceptibility as well as clinical outcomes in 312 patients with HCC and in 624 cancer-free controls. We found that carriers of the TT allele of the variant rs1047972 were at greater risk of HCC compared with wild-type (CC) carriers. Moreover, carriers of at least one A allele in rs2273535 were less likely to progress to stage III/IV disease, develop large tumors or be classified into Child-Pugh class B or C. Individuals with at least one G allele at AURKA SNP rs2064863 were at lower risk of developing large tumors or progressing to Child-Pugh grade B or C. Our results indicate that genetic variations in the AURKA gene may serve as an important predictor of early-stage HCC and be a reliable biomarker for the development of HCC.
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Affiliation(s)
- Bin Wang
- Department of Hepatobiliary Surgery, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Chin-Jung Hsu
- School of Chinese Medicine, China Medical University, Taichung, Taiwan.,Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Hsuan Chou
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Hsiang-Lin Lee
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Whei-Ling Chiang
- School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
| | - Chen-Ming Su
- Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Hsiao-Chi Tsai
- Department of Scientific Education, Qinghai Red Cross Hospital, Xining City, Qinghai, China
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chih-Hsin Tang
- Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.,Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.,Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
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24
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Wang B, Hsu CJ, Lee HL, Chou CH, Su CM, Yang SF, Tang CH. Impact of matrix metalloproteinase-11 gene polymorphisms upon the development and progression of hepatocellular carcinoma. Int J Med Sci 2018; 15:653-658. [PMID: 29725257 PMCID: PMC5930468 DOI: 10.7150/ijms.23733] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 03/02/2018] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a liver malignancy and a major cause of cancer mortality worldwide. Matrix metalloproteinase-11 (MMP-11), also known as stromelysin-3, plays a critical role during tumor migration, invasion and metastasis. Here, we report on the association between five single nucleotide polymorphisms (SNPs) - rs738791, rs2267029, rs738792, rs28382575, and rs131451 - of the MMP-11 gene and HCC susceptibility, as well as clinical outcomes, in 293 patients with HCC and in 586 cancer-free controls. We found that carriers of the CT+TT allele of the rs738791 variant were at greater risk of HCC compared with wild-type (CC) carriers. Moreover, carriers of at least one C allele (C/T+C/C genotype) at the MMP-11 SNP rs738792 were likely to progress to Child-Pugh B or C grade, while individuals with at least one C allele (C/T+C/C genotype) at the MMP-11 SNP rs28382575 were at higher risk of developing stage III/IV disease, large tumors or lymph node metastasis. We believe that genetic variations in the MMP-11 gene may help to predict early-stage HCC and act as reliable biomarkers for HCC progression.
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Affiliation(s)
- Bin Wang
- Department of Hepatobiliary Surgery, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Chin-Jung Hsu
- School of Chinese Medicine, China Medical University, Taichung, Taiwan.,Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Hsiang-Lin Lee
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chia-Hsuan Chou
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Chen-Ming Su
- Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chih-Hsin Tang
- Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.,Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.,Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
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25
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Zhang Y, Wang S, Shi Y, Cao Y, He H, Zhou S, Luo S, Wen X, Chen Y, Liu H, Xiao J, Zhang S. Associations of TERT polymorphisms with hepatocellular carcinoma risk in a Han Chinese population. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2017; 10:7776-7783. [PMID: 31966625 PMCID: PMC6965258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 04/26/2017] [Indexed: 06/10/2023]
Abstract
Genetic association analysis and functional analysis have suggested that telomerase reverse transcriptase (TERT) gene affects the predisposition to various tumors. In this study, we wanted to explore the association between TERT variants and hepatocellular carcinoma (HCC) risk in a Han Chinese population via a case-control study of 473 HCC patients and 564 controls. Sequenom Mass-ARRAY platform was applied to determine the genotype of TERT polymorphisms in these subjects. Odds ratios and 95% confidence intervals that calculated by logistic regression analysis were used to assess the association under the genotype, dominant, recessive, and additive models. The "AA" genotype frequency of TERT rs2242652 in cases was significantly lower than in controls (1.69% versus 3.72%). We found two SNPs were associated with decreased risk of HCC with or without the adjustment for age and gender: rs10069690 under an additive model (adjusted OR = 0.77, 95% CI: 0.60-0.98, P = 0.038); rs2242652 under a dominant model (adjusted OR = 0.72, 95% CI: 0.54-0.95, P = 0.022) and an additive model (adjusted OR = 0.72, 95% CI: 0.56-0.92, P = 0.009). To our knowledge, the present study is the first to show the significant association between TERT polymorphisms and HCC susceptibility in a Han Chinese population from China, which may act as a potential prognostic biomarker in HCC patients.
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Affiliation(s)
- Yingai Zhang
- Central Laboratory, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
| | - Shunlan Wang
- Central Laboratory, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
| | - Yuting Shi
- Graduate School of Inner Mongolia Medical UniversityHohhot, Inner Mongolia Autonomous Region, China
| | - Yufang Cao
- Department of Intensive Care Unit, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
| | - Haowei He
- Central Laboratory, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
| | - Shuai Zhou
- Department of Hepatobiliary Surgery, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
| | - Siqin Luo
- Central Laboratory, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
| | - Xiaohong Wen
- Central Laboratory, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
| | - Yang Chen
- Central Laboratory, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
| | - Haifang Liu
- Central Laboratory, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
| | - Jingchuan Xiao
- Central Laboratory, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
| | - Shufang Zhang
- Central Laboratory, Haikou People’s Hospital, Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou, China
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26
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Hu W, Liu PY, Yang YC, Chen PC, Su CM, Chao CC, Tang CH. Association of HMGB1 Gene Polymorphisms with Lung Cancer Susceptibility and Clinical Aspects. Int J Med Sci 2017; 14:1197-1202. [PMID: 29104475 PMCID: PMC5666552 DOI: 10.7150/ijms.20933] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 08/07/2017] [Indexed: 12/27/2022] Open
Abstract
Lung cancer is one of the most frequently diagnosed malignancies and is associated with a poor survival rate in the Chinese Han population. Analysis of genetic variants could lead to improvements in prognosis following lung cancer therapy. High-mobility group box 1 protein (HMGB1) is a ubiquitous nuclear protein found in eukaryotic cells that participates in several biological functions including immune response, cell survival, apoptosis and cancer development. We investigated the effects of HMGB1 gene polymorphisms on the risk of lung cancer progression in a Chinese Han population. Our sample of 751 participants included 372 patients with lung cancer and 379 healthy controls. Four single-nucleotide polymorphisms (SNPs) of the HMGB1 gene were examined by real-time polymerase chain reaction (RT-PCR). We found that the CT or CC+CT heterozygotes of the HMGB1 rs1045411 polymorphism reduced the risks for lung cancer, while the G/T/C haplotypes of three HMGB1 SNPs (rs1360485, rs1045411 and rs2249825) also reduced the risk for lung cancer by almost half (0.486-fold). The current study is the first to examine the risk factors associated with HMGB1 SNPs in lung cancer development in the Chinese Han population.
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Affiliation(s)
- Weiwei Hu
- Department of Thoracic Surgery, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Po-Yi Liu
- Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.,Department of Thoracic Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Yi-Chen Yang
- Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan
| | - Po-Chun Chen
- Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.,Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
| | - Chen-Ming Su
- Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Chia-Chia Chao
- Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chih-Hsin Tang
- Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.,Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
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27
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Wang LH, Wu MH, Chen PC, Su CM, Xu G, Huang CC, Tsai CH, Huang YL, Tang CH. Prognostic significance of high-mobility group box protein 1 genetic polymorphisms in rheumatoid arthritis disease outcome. Int J Med Sci 2017; 14:1382-1388. [PMID: 29200952 PMCID: PMC5707755 DOI: 10.7150/ijms.21773] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Accepted: 10/11/2017] [Indexed: 12/23/2022] Open
Abstract
Rheumatoid arthritis (RA) is a systemic inflammatory disease that causes chronic inflammation of the joints. Analysis of genetic variants offers promise for guiding treatment and improving outcomes in RA. High-mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein found in all mammal eukaryotic cells that participates in several biological functions including immune response, cell survival and apoptosis. We investigated the effects of HMGB1 gene polymorphisms on the risk of RA disease progression in a cohort of Chinese Han individuals. Four single nucleotide polymorphisms (SNPs) from the HMGB1 gene were selected and genotyped in 232 patients with RA and 353 healthy controls. We found that having one C allele in rs1360485 and one G allele in rs2249825 polymorphisms lowered the risk of RA in females. Moreover, among healthy controls, those who bore the C/G/T haplotype at SNPs rs1360485, rs2249825 and rs1412125 were at reduced risk of developing RA by 0.13-fold (p <0.05). This is the first report to examine the risk factors associated with HMGB1 SNPs in the development of RA disease in the Chinese Han population.
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Affiliation(s)
- Li-Hong Wang
- Department of Orthopedics, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Min-Huan Wu
- Physical Education Office, Tunghai University, Taichung, Taiwan.,Sports Recreation and Health Management Continuing Studies, Tunghai University, Taichung, Taiwan
| | - Po-Chun Chen
- Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
| | - Chen-Ming Su
- Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Guohong Xu
- Department of Orthopedics, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Chien-Chung Huang
- Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan
| | - Chun-Hao Tsai
- School of Medicine, China Medical University, Taichung, Taiwan.,Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Yuan-Li Huang
- Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
| | - Chih-Hsin Tang
- Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan.,Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
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28
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Wang B, Chou YE, Lien MY, Su CM, Yang SF, Tang CH. Impacts of CCL4 gene polymorphisms on hepatocellular carcinoma susceptibility and development. Int J Med Sci 2017; 14:880-884. [PMID: 28824325 PMCID: PMC5562195 DOI: 10.7150/ijms.19620] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Accepted: 05/08/2017] [Indexed: 12/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and the third most common cause of cancer mortality. In Taiwan, HCC is the second leading cause of cancer death. CCL4 (C-C chemokine ligand 4), is a macrophage inflammatory protein with a chief effect in inflammation and immune-regulation, and was documented in cancer progression by promoting instability in the tumor environment. Polymorphisms in chemokine genes help to determine host-pathogen interactions that influence chemokine levels. We investigated the effects of CCL4 gene polymorphisms on the risk of hepatocellular carcinoma (HCC) disease progression in a cohort of Taiwanese patients. We recruited total of 1,546 participants in current study, including 1,200 healthy control and 346 patients with HCC. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were examined by a real-time PCR. We found that the A/G homozygotes of CCL4 rs10491121 polymorphism reduced the risks for HCC. On the other hand, AG and GA haplotypes of 2 CCL4 SNPs (rs1049112 and rs171915) also reduced the risks for HCC by 0.025 and 0.515 fold, respectively. The present report is the first time to examine the risk factors associated with CCL4 SNPs in HCC progression in Taiwan.
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Affiliation(s)
- Bin Wang
- Department of Hepatobiliary Surgery, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Ying-Erh Chou
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan.,Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Ming-Yu Lien
- Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.,Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chen-Ming Su
- Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China
| | - Shun-Fa Yang
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.,Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Chih-Hsin Tang
- Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.,Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
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29
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Niu ZS, Niu XJ, Wang WH. Genetic alterations in hepatocellular carcinoma: An update. World J Gastroenterol 2016; 22:9069-9095. [PMID: 27895396 PMCID: PMC5107590 DOI: 10.3748/wjg.v22.i41.9069] [Citation(s) in RCA: 122] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 09/20/2016] [Accepted: 10/19/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC.
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MESH Headings
- Animals
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/metabolism
- Carcinoma, Hepatocellular/pathology
- Cell Transformation, Neoplastic/genetics
- Cell Transformation, Neoplastic/metabolism
- Cell Transformation, Neoplastic/pathology
- Gene Expression Regulation, Neoplastic
- Genetic Predisposition to Disease
- Genomic Instability
- Humans
- Liver Neoplasms/drug therapy
- Liver Neoplasms/genetics
- Liver Neoplasms/metabolism
- Liver Neoplasms/pathology
- Molecular Diagnostic Techniques
- Molecular Targeted Therapy
- Mutation
- Patient Selection
- Phenotype
- Polymorphism, Single Nucleotide
- Precision Medicine
- Predictive Value of Tests
- Signal Transduction
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