1
|
Yang JL, Yang J, Fang RF, Sai WL, Yao DF, Yao M. Hypoxia upregulates hepatic angiopoietin-2 transcription to promote the progression of hepatocellular carcinoma. World J Hepatol 2024; 16:1480-1492. [DOI: 10.4254/wjh.v16.i12.1480] [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: 06/27/2024] [Revised: 08/22/2024] [Accepted: 09/13/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Angiopoietin-2 (Ang-2) level is related to hepatocellular carcinoma (HCC) progression. However, the dynamic expression and regulatory mechanism of Ang-2 remain unclear.
AIM To investigate Ang-2 levels in chronic liver diseases and validate early monitoring value with a dynamic model in hepatocarcinogenesis.
METHODS Sprague-Dawley rats in hepatocarcinogenesis were induced with diet 2-fluorenylacet-amide, and grouped based on liver histopathology by hematoxylin and eosin staining. Differently expressed genes or Ang-2 mRNA in livers were analyzed by whole-genome microarray. Ang-2 levels in chronic liver diseases were detected by an enzyme-linked immunosorbent assay.
RESULTS Clinical observation reveled that the circulating levels of Ang-2 and hypoxia-inducible factor-1α (HIF-1α) in patients with chronic liver diseases were progressively increased from benign to HCC (P < 0.001). Dynamic model validated that the up-regulated Ang-2 in liver and blood was positively correlated with HIF-1α in hepatocarcinogenesis (P < 0.001). Mechanistically, Ang-2 was regulated by HIF-1α. When specific HIF-1α- microRNAs transfected into HCC cells, the cell proliferation significantly inhibited, HIF-1α and Ang-2 down-regulated, and also affected epithelial-mesenchymal transition via increasing E-cadherin to block cell invasion or migration with reducing of snail, twist and vimentin.
CONCLUSION Hypoxia-induced Ang-2 up-regulating expression might serve as a sensitive early monitoring biomarker for hepatocarcinogenesis or HCC metastasis.
Collapse
Affiliation(s)
- Jun-Ling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Jie Yang
- Department of Biology, Life Science School of Nantong University, Nantong 226009, Jiangsu Province, China
| | - Rong-Fei Fang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wen-Li Sai
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Deng-Fu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Min Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| |
Collapse
|
2
|
Flores Monar GV, Reynolds T, Gordon M, Moon D, Moon C. Molecular Markers for Bladder Cancer Screening: An Insight into Bladder Cancer and FDA-Approved Biomarkers. Int J Mol Sci 2023; 24:14374. [PMID: 37762677 PMCID: PMC10531979 DOI: 10.3390/ijms241814374] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 09/10/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Bladder cancer is one of the most financially burdensome cancers globally, from its diagnostic to its terminal stages. The impact it imposes on patients and the medical community is substantial, exacerbated by the absence of disease-specific characteristics and limited disease-free spans. Frequent recurrences, impacting nearly half of the diagnosed population, require frequent and invasive monitoring. Given the advancing comprehension of its etiology and attributes, bladder cancer is an appealing candidate for screening strategies. Cystoscopy is the current gold standard for bladder cancer detection, but it is invasive and has the potential for undesired complications and elevated costs. Although urine cytology is a supplementary tool in select instances, its efficacy is limited due to its restricted sensitivity, mainly when targeting low-grade tumors. Although most of these assays exhibit higher sensitivity than urine cytology, clinical guidelines do not currently incorporate them. Consequently, it is necessary to explore novel screening assays to identify distinctive alterations exclusive to bladder cancer. Thus, integrating potential molecular assays requires further investigation through more extensive validation studies. Within this article, we offer a comprehensive overview of the critical features of bladder cancer while conducting a thorough analysis of the FDA-approved assays designed to diagnose and monitor its recurrences.
Collapse
Affiliation(s)
| | - Thomas Reynolds
- NEXT Bio-Research Services, LLC, 11601 Ironbridge Road, Suite 101, Chester, VA 23831, USA;
| | - Maxie Gordon
- BCD Innovations USA, 10606 Candlewick Road, Lutherville, MD 2109, USA
| | - David Moon
- HJM Cancer Research Foundation Corporation, 10606 Candlewick Road, Lutherville, MD 2109, USA
| | - Chulso Moon
- HJM Cancer Research Foundation Corporation, 10606 Candlewick Road, Lutherville, MD 2109, USA
- BCD Innovations USA, 10606 Candlewick Road, Lutherville, MD 2109, USA
- Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Medical Institution, Cancer Research Building II, 5M3, 1550 Orleans Street, Baltimore, MD 21205, USA
| |
Collapse
|
3
|
Wang R, Lian J, Wang X, Pang X, Xu B, Tang S, Shao J, Lu H. Survival rate of colorectal cancer in China: A systematic review and meta-analysis. Front Oncol 2023; 13:1033154. [PMID: 36937415 PMCID: PMC10020492 DOI: 10.3389/fonc.2023.1033154] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 02/20/2023] [Indexed: 03/06/2023] Open
Abstract
Background This study aims to comprehensively summarize the colorectal survival rate in China. Method: In PubMed and Web of Science, keywords such as "colorectal cancer", "survival" and "China" were used to search literatures in the past 10 years. Random effect models were selected to summarize 1-year, 3-year, and 5-year survival rates, and meta-regression and subgroup analyses were performed on the included studies. Results A total of 16 retrospective and prospective studies providing survival rates for colorectal cancer in China were included. The 1-year, 3-year, and 5-year survival rates of colorectal cancer in China were 0.79, 0.72 and 0.62, respectively. In the included studies, the 5-year survival rates of stage I (5474 cases), stage II (9215 cases), stage III (8048 cases), and stage IV (4199 cases) colorectal cancer patients were 0.85, 0.81, 0.57 and 0.30, respectively. Among them, the 5-year survival rates of colorectal cancer were 0.82, 0.76, 0.71, 0.67, 0.66, 0.65 and 0.63 in Tianjin, Beijing, Guangdong, Shandong, Liaoning, Zhejiang and Shanghai, respectively. Conclusion The 5-year survival rate in China is close to that of most European countries, but still lower than Japan and South Korea, and the gap is gradually narrowing. Region, stage, differentiation, pathological type, and surgical approach can affect 5-year survival in colorectal cancer. Systematic review registration https://www.crd.york.ac.uk/prospero/ identifier, CRD42022357789.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Haibo Lu
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
| |
Collapse
|
4
|
The Influence of Clusterin Glycosylation Variability on Selected Pathophysiological Processes in the Human Body. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:7657876. [PMID: 36071866 PMCID: PMC9441386 DOI: 10.1155/2022/7657876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 08/12/2022] [Accepted: 08/16/2022] [Indexed: 11/17/2022]
Abstract
The present review gathers together the most important information about variability in clusterin molecular structure, its profile, and the degree of glycosylation occurring in human tissues and body fluids in the context of the utility of these characteristics as potential diagnostic biomarkers of selected pathophysiological conditions. The carbohydrate part of clusterin plays a crucial role in many biological processes such as endocytosis and apoptosis. Many pathologies associated with neurodegeneration, carcinogenesis, metabolic diseases, and civilizational diseases (e.g., cardiovascular incidents and male infertility) have been described as causes of homeostasis disturbance, in which the glycan part of clusterin plays a very important role. The results of the discussed studies suggest that glycoproteomic analysis of clusterin may help differentiate the severity of hippocampal atrophy, detect the causes of infertility with an immune background, and monitor the development of cancer. Understanding the mechanism of clusterin (CLU) action and its binding epitopes may enable to indicate new therapeutic goals. The carbohydrate part of clusterin is considered necessary to maintain its proper molecular conformation, structural stability, and proper systemic and/or local biological activity. Taking into account the wide spectrum of CLU action and its participation in many processes in the human body, further studies on clusterin glycosylation variability are needed to better understand the molecular mechanisms of many pathophysiological conditions. They can also provide the opportunity to find new biomarkers and enrich the panel of diagnostic parameters for diseases that still pose a challenge for modern medicine.
Collapse
|
5
|
Yao M, Yang JL, Wang DF, Wang L, Chen Y, Yao DF. Encouraging specific biomarkers-based therapeutic strategies for hepatocellular carcinoma. World J Clin Cases 2022; 10:3321-3333. [PMID: 35611205 PMCID: PMC9048543 DOI: 10.12998/wjcc.v10.i11.3321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/10/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
The prevention, early discovery and effective treatment of patients with hepatocellular carcinoma (HCC) remain a global medical challenge. At present, HCC is still mainly treated by surgery, supplemented by vascular embolization, radio frequency, radiotherapy, chemotherapy and biotherapy. The application of multikinase inhibitor sorafenib, chimeric antigen receptor T cells, or PD-1/PD-L1 inhibitors can prolong the median survival of HCC patients. However, the treatment efficacy is still unsatisfactory due to HCC metastasis and postoperative recurrence. During the process of hepatocyte malignant transformation, HCC tissues can express and secrete many types of specific biomarkers, or oncogenic antigen molecules into blood, for example, alpha-fetoprotein, glypican-3, Wnt3a (one of the key signaling molecules in the Wnt/β-catenin pathway), insulin-like growth factor (IGF)-II or IGF-I receptor, vascular endothelial growth factor, secretory clusterin and so on. In addition, combining immunotherapy with non-coding RNAs might improve anti-cancer efficacy. These biomarkers not only contribute to HCC diagnosis or prognosis, but may also become molecular targets for HCC therapy under developing or clinical trials. This article reviews the progress in emerging biomarkers in basic research or clinical trials for HCC immunotherapy.
Collapse
Affiliation(s)
- Min Yao
- Research Center of Clinical Medicine & Department of Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Jun-Ling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - De-Feng Wang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Li Wang
- Department of Medical Informatics, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Ying Chen
- Department of Oncology, Affiliated Second Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Deng-Fu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| |
Collapse
|
6
|
Jiang Y, Yuan H, Li Z, Ji X, Shen Q, Tuo J, Bi J, Li H, Xiang Y. Global pattern and trends of colorectal cancer survival: a systematic review of population-based registration data. Cancer Biol Med 2021; 19:j.issn.2095-3941.2020.0634. [PMID: 34486877 PMCID: PMC8832952 DOI: 10.20892/j.issn.2095-3941.2020.0634] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 04/25/2021] [Indexed: 12/05/2022] Open
Abstract
This review will describe the global patterns and trends of colorectal cancer survival, using data from the population-based studies or cancer registration. We performed a systematic search of China National Knowledge Infrastructure (CNKI), Wanfang Data, PubMed, Web of Science, EMBASE, and SEER and collected all population-based survival studies of colorectal cancer (up to June 2020). Estimates of observed and relative survival rates of colorectal cancer by sex, period, and country were extracted from original studies to describe the temporal patterns and trends from the late 1990s to the early 21st century. Globally, 5-year observed survival rates were higher in Seoul, Republic of Korea (1993-1997; 56.8% and 54.3% for colon and rectum cancers, respectively), Zhejiang province (2005-2010; 52.9% for colon cancer), Tianjin (1991-1999; 52.5% for colon cancer), Shanghai (2002-2006; 50.0% for rectum cancer) of China, and in Japan (1993-1996, 59.6% for colorectal cancer). Five-year relative survival rates of colorectal cancer in the Republic of Korea (2010-2014), Queensland, Australia (2005-2012), and the USA (2005-2009) ranked at relatively higher positions compared to other countries. In general, colorectal cancer survival rates are improving over time worldwide. Sex disparities in survival rates were also observed in the colon, rectum, and colorectal cancers in most countries or regions. The poorest age-specific 5-year relative survival rate was observed in patients > 75 years of age. In conclusion, over the past 3 decades, colorectal cancer survival has gradually improved. Geographic variations, sex differences, and age gradients were also observed globally in colorectal cancer survival. Further studies are therefore warranted to investigate the prognostic factors of colorectal cancer.
Collapse
Affiliation(s)
- Yufei Jiang
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Huiyun Yuan
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhuoying Li
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Xiaowei Ji
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Qiuming Shen
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jiayi Tuo
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Jinghao Bi
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Honglan Li
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Yongbing Xiang
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
- Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| |
Collapse
|
7
|
Wu MN, Zheng WJ, Ye WX, Wang L, Chen Y, Yang J, Yao DF, Yao M. Oncogenic tuftelin 1 as a potential molecular-targeted for inhibiting hepatocellular carcinoma growth. World J Gastroenterol 2021; 27:3327-3341. [PMID: 34163115 PMCID: PMC8218352 DOI: 10.3748/wjg.v27.i23.3327] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/06/2021] [Accepted: 05/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Abnormal tuftelin 1 (TUFT1) has been reported in multiple cancers and exhibits oncogenic roles in tumor progression. However, limited data are available on the relationship between TUFT1 and hepatocellular carcinoma (HCC), and the exact biological mechanism of TUFT1 is still poorly understood in HCC. AIM To investigate TUFT1 expression in HCC and how interfering TUFT1 transcription affects HCC growth. METHODS TUFT1 in HCC and non-HCC tissues based on databases of the Cancer Genome Atlas and Oncomine were analyzed, and TUFT1 in human HCC tissues on microarray were detected by immunohistochemistry for clinicopathological features, overall survival, and disease-free survival. HCC cells were transfected with constructed vectors of TUFT1 that interfere or over-express TUFT1 for analyzing the biological behaviors of HCC cells. Proliferation, invasion, migration, and apoptosis of cells were detected by cell counting kit-8, scratch assay, transwell tests, and flow cytometry and confirmed by Western blotting, respectively. RESULTS Abnormal TUFT1 levels in databases expressed in HCC at messenger RNA (mRNA) level and HCC tissues were mainly located in cytoplasm and membrane. The level of TUFT1 expression in the HCC group was significantly higher (χ 2 = 18.563, P < 0.001) than that in the non-cancerous group, closely related to clinical staging, size, vascular invasion of tumor, hepatitis B e-antigen positive, and ascites (P < 0.01) of HCC patients, and negatively to HCC patients' overall survival and disease-free survival (P < 0.001). After interfering with TUFT1 transcription at mRNA level in the MHCC-97H cells by the specific TUFT1-short hairpin RNA, cell proliferation, invasion, and metastasis were significantly inhibited with increasing apoptosis rate. In contrast, proliferation, invasion, and migration were significantly enhanced after over-expression of TUFT1 mRNA in Hep3B cells in vitro. CONCLUSION Oncogenic TUFT1 was associated with the progression of HCC and could be a potential molecular-target for inhibiting HCC growth.
Collapse
Affiliation(s)
- Meng-Na Wu
- Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wen-Jie Zheng
- Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wen-Xin Ye
- Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Li Wang
- Department of Medical Informatics, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Ying Chen
- Department of Oncology, The Affiliated Second Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Jie Yang
- Department of Molecular Biology, Life Science School of Nantong University, Nantong 226009, Jiangsu Province, China
| | - Deng-Fu Yao
- Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Min Yao
- Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| |
Collapse
|
8
|
Association of cancer screening and residing in a coal-polluted East Asian region with overall survival of lung cancer patients: a retrospective cohort study. Sci Rep 2020; 10:17432. [PMID: 33060705 PMCID: PMC7566617 DOI: 10.1038/s41598-020-74082-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 09/23/2020] [Indexed: 11/08/2022] Open
Abstract
Lung cancer is the leading cause of cancer death worldwide. The Xuanwei-Fuyuan (XF) region of Yunnan, China has a high incidence of lung cancer from coal-related pollution. Effort to raise public awareness screening for lung cancer has been ongoing. We retrospectively analyzed overall survival (OS) of lung cancer patients of a tertiary cancer center in Yunnan to investigate screening and regional residential status as predictive factors. Consecutive cases of newly diagnosed lung cancer were reviewed. The lung cancer cases diagnosed by screening were more likely to be early-staged and treated by surgery than those diagnosed not by screening. In patients diagnosed not by screening, XF residential status was a significant predictor of improved OS. Frailty model detected significant heterogeneity associated with region of residence in unscreened patients. Potential biases associated with screening were examined by Monte Carlo simulations and sensitivity analyses. Focused effort in cancer screening and increased public awareness of pollution-related lung cancer in XF might have led to early diagnosis and improved OS, and increased investment in health care resources in high risk areas may have produced additional unobserved factors that underlay the association of XF residential status with improved OS in patients diagnosed not by screening.
Collapse
|
9
|
Sai WL, Yao M, Shen SJ, Zheng WJ, Sun JY, Wu MN, Wang L, Yao DF. Dynamic expression of hepatic GP73 mRNA and protein and circulating GP73 during hepatocytes malignant transformation. Hepatobiliary Pancreat Dis Int 2020; 19:449-454. [PMID: 32171652 DOI: 10.1016/j.hbpd.2020.02.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Accepted: 02/19/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatic Golgi protein-73 (GP73) expression is related to hepatocellular carcinoma (HCC) progression. The aim of this study was to investigate the dynamic expression of GP73 mRNA and protein during hepatocytes malignant transformation. METHODS Human GP73 expressions in 88 HCC tissues and their self-control surrounding tissues were examined by immunohistochemistry, and survival time of HCC patients was evaluated by the Kaplan-Meier method. HCC model of Sprague-Dawley rats was made by diet containing 2-fluorenylacetamide. The rats were divided into the control, hepatocyte degeneration, precanceration, and HCC groups to observe GP73 protein and mRNA alterations during hepatocytes malignant transformation. RESULTS The GP73 expression was significantly higher in the cancerous tissues than that in the surrounding tissues, with shorter survival time, and the positive rates of GP73 protein in human HCC tissues were 53.3% at stage I, 84.0% at stage II, 84.6% at stage III, and 60.0% at stage IV, respectively. The positive rates of hepatic GP73 protein and mRNA in the rat models were none in the control group, 66.7% and 44.4% in the hepatocytes degeneration group, 88.9% and 77.8% in the hepatocytes precanceration group, and 100% in the HCC group, respectively. There was a positive correlation (r = 0.91, P<0.01) between hepatic GP73 and serum GP73 during rat hepatocytes malignant transformation. CONCLUSIONS Abnormal GP73 expression may be a sensitive and valuable biomarker in hepatocarcinogensis.
Collapse
MESH Headings
- Adult
- Aged
- Animals
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/metabolism
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/pathology
- Cell Transformation, Neoplastic/genetics
- Cell Transformation, Neoplastic/metabolism
- Cell Transformation, Neoplastic/pathology
- Female
- Gene Expression Regulation, Neoplastic
- Hepatocytes/metabolism
- Hepatocytes/pathology
- Humans
- Liver Neoplasms/genetics
- Liver Neoplasms/metabolism
- Liver Neoplasms/mortality
- Liver Neoplasms/pathology
- Male
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Middle Aged
- Neoplasm Staging
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Rats, Sprague-Dawley
- Time Factors
Collapse
Affiliation(s)
- Wen-Li Sai
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China; Departments of Medical Immunology & Medical Informatics, Medical College of Nantong University, Nantong 226001, China
| | - Min Yao
- Departments of Medical Immunology & Medical Informatics, Medical College of Nantong University, Nantong 226001, China
| | - Shui-Jie Shen
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China; Department of Oncology, Nantong Hospital of Traditional Chinese Medicine, Nantong 226001, China
| | - Wen-Jie Zheng
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Jian-Ying Sun
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Meng-Na Wu
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Li Wang
- Departments of Medical Immunology & Medical Informatics, Medical College of Nantong University, Nantong 226001, China
| | - Deng-Fu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
| |
Collapse
|
10
|
Yao M, Sai W, Zheng W, Wang L, Dong Z, Yao D. Secretory Clusterin as a Novel Molecular-targeted Therapy for Inhibiting Hepatocellular Carcinoma Growth. Curr Med Chem 2020; 27:3290-3301. [PMID: 31232234 DOI: 10.2174/0929867326666190624161158] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2018] [Revised: 03/19/2019] [Accepted: 05/28/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Although secretory clusterin (sCLU) plays a crucial role in Hepatocellular Carcinoma (HCC) cells proliferation, Multiple Drug Resistance (MDR), metastasis and so on, its targeted effects and exact mechanism are still unknown. This review summarizes some new progress in sCLU as a molecular-targeted therapy in the treatment of HCC. METHODS A systematic review of the published English-language literature about sCLU and HCC has been performed using the PubMed and bibliographic databases. Some valuable studies on sCLU in HCC progression were searched for relevant articles with the keywords: HCC, diagnosis, MDR, as molecular-targeted in treatment, and so on. RESULTS The incidence of the positive rate of sCLU was significantly higher in HCC tissues as compared to the surrounding tissues at mRNA or protein level, gradually increasing with tumor-nodemetastasis staging (P<0.05). Also, the abnormal level of sCLU was related to poor differentiation degree, and considered as a useful marker for HCC diagnosis or independent prognosis for patients. Hepatic sCLU could be silenced at mRNA level by specific sCLU-shRNA or by OGX-011 to inhibit cancer cell proliferation with an increase in apoptosis, cell cycle arrest, reversal MDR, alteration of cell migration or invasion behaviors, and a decrease in GSK-3β or AKT phosphorylation in vitro, as well as significant suppression of the xenograft growth by down-regulating β-catenin, p-GSK3β, and cyclinD1 expression in vivo. CONCLUSION Abnormal hepatic sCLU expression should not only be a new diagnostic biomarker but also a novel promising target for inhibiting HCC growth.
Collapse
Affiliation(s)
- Min Yao
- Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wenli Sai
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wenjie Zheng
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Li Wang
- Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Zhizhen Dong
- Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Dengfu Yao
- Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| |
Collapse
|
11
|
Zheng W, Yao M, Fang M, Pan L, Wang L, Yang J, Dong Z, Yao D. Oncogenic Wnt3a: A Candidate Specific Marker and Novel Molecular Target for Hepatocellular Carcinoma. J Cancer 2019; 10:5862-5873. [PMID: 31737122 PMCID: PMC6843874 DOI: 10.7150/jca.31599] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 08/20/2019] [Indexed: 12/22/2022] Open
Abstract
Background and aim: It is of the utmost importance for the specific diagnosis and effective therapy of hepatocellular carcinoma (HCC). Abnormality of oncogenic Wingless-type MMTV integration site family member 3a (Wnt3a) has been associated with progression of HCC. In this study, we aimed to evaluate Wnt3a as a novel biomarker and target for HCC. Methods: Circulating Wnt3a levels were quantitatively detected in a cohort of chronic liver diseases by an enzyme-linked immune-absorbent assay (ELISA). Hepatic Wnt3a expression in HCC and para-cancerous tissues was analyzed by immunohistochemistry. Prognostic value of Wnt3a for HCC was discovered in the cohort from the Cancer Genome Atlas (TCGA). Dynamic alterations of Wnt3a levels were detected in the hepatocarcinogenesis model induced by 2-acetylaminofluorene. Effects of Wnt3a on biological behaviors were evaluated in vitro and in vivo based on Crispr/Cas9. Results: Up-regulated Wnt3a levels were observed in serum of HCC patients with high specificity and sensitivity for HCC diagnosis. Combination of Wnt3a and AFP could improve sensitivity to 93.9% in serological detection. In addition, Wnt3a expression in HCC tissues was significantly higher than that in para-cancerous tissues. The cohort of TCGA demonstrated that high Wnt3a expression led to a poor survival of HCC patients, especially in cases at advanced stages. Furthermore, the hepatocarcinogenesis model showed that Wnt3a dynamically increased in the development of HCC. Functionally, silencing Wnt3a by Crispr/Cas9 suppressed the proliferation, colony formation, induced cell cycle arrest of HCC cells by de-activating Wnt/β-catenin pathway in vitro, and inhibited xenograft tumor growth in vivo. Conclusions: Oncogenic Wnt3a could be considered as a candidate biomarker and novel target for HCC.
Collapse
Affiliation(s)
- Wenjie Zheng
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Min Yao
- Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Miao Fang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Liuhong Pan
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Li Wang
- Department of Medical Informatics, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Junling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Zhizhen Dong
- Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Dengfu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| |
Collapse
|
12
|
Fang M, Yao M, Wang L, Yao DF. Food for thought on hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2019; 18:493-494. [PMID: 31047806 DOI: 10.1016/j.hbpd.2019.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 04/09/2019] [Indexed: 02/05/2023]
Affiliation(s)
- Miao Fang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Min Yao
- Department of Immunology, Medical School of Nantong University, Nantong 226001, China
| | - Li Wang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Deng-Fu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
| |
Collapse
|
13
|
Hou H, Meng Z, Zhao X, Ding G, Sun M, Wang W, Wang Y. Survival of Esophageal Cancer in China: A Pooled Analysis on Hospital-Based Studies From 2000 to 2018. Front Oncol 2019; 9:548. [PMID: 31316913 PMCID: PMC6610307 DOI: 10.3389/fonc.2019.00548] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Accepted: 06/05/2019] [Indexed: 12/31/2022] Open
Abstract
Background: Esophageal cancer (EC) causes more than 400 thousand deaths per year, and half of them occur in China. There are discrepancies regarding the survival of EC patients between population-based surveillance studies and hospital-based studies. Objectives: We aimed to synthesize the survival data from hospital-based EC studies in the Chinese population from 2000 to 2018 and to compare the survival rates between EC patients with different clinical classifications. Methods: The protocol of this systematic review was registered in PROSPERO (CRD-42019121559). We searched Embase, PubMed, CNKI, and Wanfang databases for studies published between January 1, 2000 and December 31, 2018. We calculated the pooled survival rates and 95% confidence intervals (CIs) by Stata software (V14.0). Results: Our literature search identified 933 studies, of which 331 studies with 79,777 EC patients met the inclusion criteria and were included in meta-analyses. The pooled survival rates were 74.1% (95% CI: 72.6–75.7%) for 1-year survival, 49.0% (95% CI: 44.2–53.8%) for 2-years survival, 46.0% (95% CI: 42.6–49.5%) for 3-years survival, and 40.1% (95% CI: 33.7–46.4%) for 5-years survival. An increased tendency toward EC survival was verified from 2000 to 2018. In addition, discrepancies were observed between EC patients with different clinical classifications (e.g., stages, histologic types, and cancer sites). Conclusions: Our findings showed a higher survival rate in hospital-based studies than population-based surveillance studies. Although this hospital-based study is subject to potential representability and publication bias, it offers insight into the prognosis of patients with EC in China.
Collapse
Affiliation(s)
- Haifeng Hou
- School of Public Health, Taishan Medical University, Taian, China
| | - Zixiu Meng
- School of Public Health, Taishan Medical University, Taian, China
| | - Xuan Zhao
- School of Public Health, Taishan Medical University, Taian, China
| | - Guoyong Ding
- School of Public Health, Taishan Medical University, Taian, China
| | - Ming Sun
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| | - Wei Wang
- School of Public Health, Taishan Medical University, Taian, China.,School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
| | - Youxin Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China
| |
Collapse
|
14
|
Tai BJ, Yao M, Zheng WJ, Shen YC, Wang L, Sun JY, Wu MN, Dong ZZ, Yao DF. Alteration of oncogenic IGF-II gene methylation status associates with hepatocyte malignant transformation. Hepatobiliary Pancreat Dis Int 2019; 18:158-163. [PMID: 30692043 DOI: 10.1016/j.hbpd.2019.01.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 12/31/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND Oncogenic insulin-like growth factor-II (IGF-II) is overexpressed in hepatocellular carcinoma (HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its molecular mechanism in HCC progression. METHODS IGF-II alterations were observed in rat hepatocarcinogenesis models induced by 2-acetylaminofluorene. Liver IGF-II expression was compared by immunohistochemistry or tissue IGF-II specific concentration (nmol/mg protein). Status of human IGF-II promoter 3 (P3) or rat IGF-II P2 CpG site methylation was amplified by methylation-specific polymerase chain reaction (MSP). Serum IGF-II levels were quantitatively detected by an enzyme-linked immunosorbent assay. RESULTS The levels of hepatic IGF-II expression were significantly elevated in the HCC group (P < 0.001). The unmethylation rate of IGF-II P3 CpG sites was 100% in the HCC-, 52.5% in the paracancerous-, and none (0%) in the distal noncancerous-tissues. Abnormal IGF-II expression was related to differentiation degree, tumor invasion, and positive HBV-DNA (all P < 0.001), with a negative correlation between P3 methylation degree and IGF-II expression. There was a positive correlation between liver IGF-II specific concentration and circulating IGF-II level (r = 0.97, P < 0.001). Significantly negative correlation was found between IGF-II P2 CpG site methylation and circulating IGF-II (rs = -0.89, P < 0.001) or liver IGF-II level (rs = -0.84, P < 0.001). CONCLUSIONS The increase of serum IGF-II and the alteration of oncogenic gene IGF-II methylation may be biomarkers for HCC diagnosis and DNA methylation may be the therapeutic target of HCC.
Collapse
Affiliation(s)
- Bo-Jun Tai
- Department of Infectious Diseases, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Min Yao
- Department of Immunology, Medical School of Nantong University, Nantong 226001, China
| | - Wen-Jie Zheng
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Yu-Cheng Shen
- Department of Oncology, Affiliated Haian Hospital of Nantong University, Nantong 226601, China
| | - Li Wang
- Department of Immunology, Medical School of Nantong University, Nantong 226001, China
| | - Jian-Ying Sun
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Meng-Na Wu
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Zhi-Zhen Dong
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Deng-Fu Yao
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China.
| |
Collapse
|
15
|
Zheng W, Yang J, Dong Z, Wang L, Fang M, Wu W, Yao D, Yao M. High mobility group box 3 as an emerging biomarker in diagnosis and prognosis of hepatocellular carcinoma. Cancer Manag Res 2018; 10:5979-5989. [PMID: 30538547 PMCID: PMC6255278 DOI: 10.2147/cmar.s181742] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
PURPOSE High mobility group box 3 (HMGB3) is associated with hepatocytes malignant transformation by our previous work. We continued to investigate the diagnostic and prognostic values of HMGB3 for hepatocellular carcinoma (HCC). PATIENTS AND METHODS Circulating HMGB3 levels were quantitatively detected in a cohort of 225 patients with chronic liver diseases by ELISA and compared with alpha-fetoprotein by the receiver operating characteristic curve. HMGB3 expression in tissues of 170 HCC was detected by tissue microarray and immunohistochemistry. Relationship between HMGB3 level and HCC prognosis was evaluated by the Kaplan-Meier curves and Cox regression model. RESULTS The incidence of serum HMGB3 >2.0 ng/mL was 75.6% in HCC (96/127), 20.8% in liver cirrhosis (10/48), 16.0% in chronic hepatitis (8/50), and none in healthy controls (0/49). Significant difference (P<0.001) of circulating HMGB3 level was found between HCC and benign liver diseases. Total diagnostic sensitivity of serum HMGB3 plus alpha-fetoprotein was up to 89.0% for HCC. Higher HMGB3 expression was confirmed to be 73.5% in HCC tissues (125/170) >30.6% in their paracancerous tissues (52/170). HMGB3 expression was closely related to tumor size, TNM stage, poor survival, and high recurrence, suggesting an independent prognosis factor for HCC. CONCLUSION HMGB3 with aberrant expression could be a novel diagnostic and prognostic marker for HCC.
Collapse
Affiliation(s)
- Wenjie Zheng
- Medical School of Nantong University, Nantong 226001, Jiangsu, China, ,
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China,
| | - Junling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China,
| | - Zhizhen Dong
- Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China
| | - Li Wang
- Medical School of Nantong University, Nantong 226001, Jiangsu, China, ,
| | - Miao Fang
- Medical School of Nantong University, Nantong 226001, Jiangsu, China, ,
| | - Wei Wu
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China,
| | - Dengfu Yao
- Medical School of Nantong University, Nantong 226001, Jiangsu, China, ,
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China,
| | - Min Yao
- Medical School of Nantong University, Nantong 226001, Jiangsu, China, ,
| |
Collapse
|
16
|
Yao M, Fang M, Zheng W, Dong Z, Yao D. Role of secretory clusterin in hepatocarcinogenesis. Transl Gastroenterol Hepatol 2018; 3:48. [PMID: 30221206 DOI: 10.21037/tgh.2018.07.13] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Accepted: 07/30/2018] [Indexed: 12/21/2022] Open
Abstract
Secretory clusterin (sCLU) is a small stress-induced cytoprotective chaperone protein. Its biological functions are similar to those of a heat-shock protein. The sCLU plays a crucial role in cell proliferation, multiple drug resistance, metastasis, and tumor progression. Abnormal sCLU expression in tumor tissues or sera of patients with primary hepatic cancer has been considered a useful biomarker for diagnosis and surveillance. However, the exact relationship between sCLU overexpression and malignant transformation of hepatocytes is still unknown. The present review examines some novel advances of the knowledge about the oncogenic role of sCLU in hepatocarcinogenesis.
Collapse
Affiliation(s)
- Min Yao
- Medical School of Nantong University, Nantong 226001, China.,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Miao Fang
- Medical School of Nantong University, Nantong 226001, China
| | - Wenjie Zheng
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Zhizhen Dong
- Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, China
| | - Dengfu Yao
- Medical School of Nantong University, Nantong 226001, China.,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
| |
Collapse
|
17
|
Chen JG, Chen HZ, Zhu J, Yang YL, Zhang YH, Huang PX, Chen YS, Zhu CY, Yang LP, Shen K, Qiang FL, Wang GR. Cancer survival in patients from a hospital-based cancer registry, China. J Cancer 2018; 9:851-860. [PMID: 29581763 PMCID: PMC5868149 DOI: 10.7150/jca.23039] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 01/28/2018] [Indexed: 02/04/2023] Open
Abstract
Purpose: There are few reports on survival rate analysis from hospital-based cancer registries (HBCR) in China, although the National Center of Cancer Registry of China has launched such an effort with the mission to expand the scope of registration and follow-up. Our study aimed to evaluate survival and outcomes of cancer patients from a HBCR in eastern China. Methods: Active and passive follow-up methods were used to obtain information on survival status for all patients from Qidong City and Haimen City in the databases of our hospital-based registrations from 2002 to 2014. Censor time for survival was 31st March, 2016. Survival probability was estimated using the life-table method with SPSS Statistics software, and comparison of significant differences in survival rates was tested by Wilcoxon (Gehan) statistic. Results: The outcomes of 5010 patients were identified in the follow-up for 5244 cases from Qidong and Haimen, with a follow-up rate of 95.65%, and a rate of lost to follow-up of 4.35%. The 1-, 3-, 5-, and 10-year observed survival (OS) rate in all-combined cancer sites were 59.80%, 37.70%, 30.82%, and 22.60%, respectively. The top 10 cancer sites in rank were cancers of lung, esophagus, liver, cervix, stomach, breast, colon-rectum, non-Hodgkin's lymphoma, nasopharynx, and ovary, with 5-year OS rates of 12.63%, 19.62%, 11.69%, 66.61%, 21.35%, 59.43%, 36.36%, 37.03%, 48.95% and 36.17%, respectively. Females experienced better survival than males for lung, esophageal, liver, nasopharyngeal and pancreatic cancers (P<0.05), but not for other sites (P>0.05). A significant difference was also found between males and females when all-sites were combined (P<0.01). There are significant differences (P<0.05) between the 2015 patients (from Qidong) and the 3001 patients (from Haimen) with 5-year OS rates of 32.72% vs 29.57%; no significant differences were found for 5-year OS rates for individual cancer sites (P>0.05) except for liver (P=0.0005) and ovary (P=0.0460) between the two cities. Younger patients had better prognosis, but significance was only seen in cervical (P=0.0102) and nasopharyngeal (P=0.0305) cancers. Conclusion: The survival rates of each site or of all sites-combined in this setting are consistent with those elsewhere in China and abroad. Discrepancies in overall survival could be affected by the proportion of sites with or without better prognosis. Hospital-based cancer survival is a better index to evaluate outcomes that reflect the levels of comprehensive treatment and improvement of medical and health services.
Collapse
Affiliation(s)
- Jian-Guo Chen
- Nantong University Tumor Hospital / Institute, 226361 Nantong, China.,Qidong Liver Cancer Institute, 226200 Qidong, China
| | - Hai-Zhen Chen
- Nantong University Tumor Hospital / Institute, 226361 Nantong, China
| | - Jian Zhu
- Qidong Liver Cancer Institute, 226200 Qidong, China
| | - Yan-Lei Yang
- Haimen City Center for Disease Control and Prevention, 226100 Haimen, China
| | | | - Pei-Xin Huang
- Haimen City Center for Disease Control and Prevention, 226100 Haimen, China
| | | | - Chao-Yong Zhu
- Nantong University Tumor Hospital / Institute, 226361 Nantong, China
| | - Li-Ping Yang
- Nantong University Tumor Hospital / Institute, 226361 Nantong, China
| | - Kang Shen
- Nantong University Tumor Hospital / Institute, 226361 Nantong, China
| | - Fu-Lin Qiang
- Nantong University Tumor Hospital / Institute, 226361 Nantong, China
| | - Gao-Ren Wang
- Nantong University Tumor Hospital / Institute, 226361 Nantong, China
| |
Collapse
|
18
|
Duong C, Nguyen T, Sheppard JP, Ong V, Chung LK, Nagasawa DT, Yang I. Genomic and Molecular Characterization of Brain Tumors in Asian and Non-Asian Patients of Los Angeles: A Single Institution Analysis. Brain Tumor Res Treat 2017; 5:64-69. [PMID: 29188206 PMCID: PMC5700029 DOI: 10.14791/btrt.2017.5.2.64] [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: 08/23/2017] [Revised: 08/24/2017] [Accepted: 09/21/2017] [Indexed: 01/01/2023] Open
Abstract
Background Worldwide, approximately 2% of new cancers are of the brain. Five-year survival rates among brain cancer patients have been reported as a little over a third. Differences in clinical outcomes between brain tumor patients of different races remain poorly understood. Methods A retrospective chart review was performed on brain tumor resection patients≥18 years old. Demographics, treatment variables, and survival outcomes were collected. Primary outcomes were length of stay, recurrence rate, progression-free survival (PFS), and overall survival (OS). Results A total of 452 patients were included in analysis. Females and males had nearly a 1:1 ratio (n=242 and n=220, respectively). Mean age was 54.8 years (SD: 14.5 range: 18–90). Females composed 69% (n=48) of Asian patients; males constituted 31% (n=22). Mean age of the Asian patients was 55.9 years (SD: 14.6 range: 26–89). Asian-only cohort tumor pathologies included glioblastoma (GBM) (n=14), high-grade glioma (n=7), low-grade glioma (n=4), meningioma (n=38), and metastases (n=7). Of the 185 meningioma patients, non-Asian patients comprised 79% of the group (n=146). Of the 65 GBM patients in total, non-Asian patients made up 89% of the GBM cohort (n=58). There were no statistically significant differences between these groups of both cohorts in recurrence (p=0.1580 and p=0.6294, respectively), PFS (p=0.9662 and p=0.4048, respectively), or OS (p=0.3711 and p=0.8183, respectively). Conclusion Studies evaluating the survival between patients of different racial backgrounds against several tumor varieties are rare. Patients of certain racial backgrounds may need additional consideration when being attended to despite the same mutational composition as their counterparts. Repeated studies using national databases may yield more conclusive results.
Collapse
Affiliation(s)
- Courtney Duong
- Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Thien Nguyen
- Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - John P Sheppard
- Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Vera Ong
- Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Lawrance K Chung
- Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Daniel T Nagasawa
- Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| | - Isaac Yang
- Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.,Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.,Department of Head and Neck Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.,Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.,Los Angeles Biomedical Research Institute, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.,Harbor-UCLA Medical Center, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA
| |
Collapse
|
19
|
Evaluation of the NMP22 BladderChek test for detecting bladder cancer: a systematic review and meta-analysis. Oncotarget 2017; 8:100648-100656. [PMID: 29246009 PMCID: PMC5725051 DOI: 10.18632/oncotarget.22065] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 09/03/2017] [Indexed: 12/11/2022] Open
Abstract
Background We examined the usefulness of the nuclear matrix protein 22 (NMP22) BladderChek test for detecting bladder cancer. Materials and Methods A literature search was performed using PubMed, Embase, the Cochrane Library, and Web of Science. The diagnostic accuracy of the NMP22 BladderChek test was evaluated via pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under curve (AUC). Inter-study heterogeneity was explored using meta-regression and subgroup analyses. Results We included 23 studies in the systematic review and 19 in the quantitative meta-analysis. Overall sensitivity and specificity were 56% (52-59%) and 88% (87-89%), respectively; pooled PLR and NLR were 4.36 (3.02-6.29) and 0.51 (0.40-0.66), respectively; DOR was 9.29 (5.55-15.55) with an AUC of 0.8295. The mean sensitivity for Ta, T1, ≥ T2, Tis, G1, G2, and G3 disease was 13.68%, 29.49%, 74.03%, 34.62%, 44.16%, 56.25%, and 67.34%, respectively. Conclusions The NMP22 BladderChek test shows good discrimination ability for detecting bladder cancer and a high-specificity algorithm that can be used for early detection to rule out patients with higher bladder cancer risk. It also has better potential for screening higher-grade and higher-stage tumors, and better diagnostic performance in Asians.
Collapse
|