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      Identification of a novel miRNA-based recurrence and prognosis prediction biomarker for hepatocellular carcinoma

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          Abstract

          Background

          A high recurrence rate has always been a serious problem for treatment of hepatocellular carcinoma (HCC). Exploring predictors of postoperative and posttransplantation recurrence in patients with HCC can guide treatment strategies for clinicians.

          Results

          In this study, logistic regression and multivariate Cox regression models were constructed with microRNA expression profile data from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO). The accuracy of predictions was assessed using receiver operating characteristic curve (ROC) and Kaplan‒Meier survival curve analyses. The results showed that the combination of 10 miRNAs (including hsa-miR-509-3p, hsa-miR-769-3p, hsa-miR-671-3p, hsa-miR-296-5p, hsa-miR-767-5p, hsa-miR-421, hsa-miR-193a-3p, hsa-miR-139-3p, hsa-miR-342-3p, and hsa-miR-193a-5p) accurately predicted postoperative and posttransplantation malignancy recurrence in HCC patients and was also valuable for prognostic evaluation of HCC patients. The 10-miRNA prediction model might assist doctors in making prognoses for HCC patients who have a high probability of relapse following surgery and in offering additional, individualized treatment to lessen that risk.

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          Most cited references34

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.

            The role of orthotopic liver transplantation in the treatment of patients with cirrhosis and hepatocellular carcinoma is controversial, and determining which patients are likely to have a good outcome after liver transplantation is difficult. We studied 48 patients with cirrhosis who had small, unresectable hepatocellular carcinomas and who underwent liver transplantation. In 94 percent of the patients, the cirrhosis was related to infection with hepatitis B virus, hepatitis C virus, or both. The presence of tumor was confirmed by biopsy or serum alpha-fetoprotein assay. The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors. Thirty-three patients with sufficient hepatic function underwent treatment for the tumor, mainly chemoembolization, before transplantation. After liver transplantation, the patients were followed prospectively for a median of 26 months (range, 9 to 54). No anticancer treatment was given after transplantation. The overall mortality rate was 17 percent. After four years, the actuarial survival rate was 75 percent and the rate of recurrence-free survival was 83 percent. Hepatocellular carcinoma recurred in four patients (8 percent). The overall and recurrence-free survival rates at four years among the 35 patients (73 percent of the total) who met the predetermined criteria for the selection of small hepatocellular carcinomas at pathological review of small hepatocellular carcinomas at pathological review of the explanted liver wer 85 percent and 92 percent, respectively, whereas the rates in the 13 patients (27 percent) whose tumors exceeded these limits were 50 percent and 59 percent, respectively (P=0.01 for overall survival; P=0.002 for recurrence-free survival). In this group of 48 patients with early-stage tumors, tumor-node-metastasis status, the number of tumors, the serum alphafetoprotein concentration, treatment received before transplantation, and 10 other variables were not significantly correlated with survival. Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.
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              Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study.

              Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant)
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                Author and article information

                Contributors
                zxfujs@126.com
                zd950812@163.com
                xuefengbu05@163.com
                zhaomengxi196335@2008.sina.com
                lboclong@aliyun.com
                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central (London )
                1471-2105
                14 November 2022
                14 November 2022
                2022
                : 23
                : 479
                Affiliations
                [1 ]GRID grid.452207.6, ISNI 0000 0004 1758 0558, Center of Hepatobiliary Pancreatic Disease, , XuZhou Central Hospital, ; Xuzhou, Jiangsu People’s Republic of China
                [2 ]GRID grid.252957.e, ISNI 0000 0001 1484 5512, Bengbu Medical College, ; Bengbu, Anhui People’s Republic of China
                [3 ]GRID grid.452247.2, Department of General Surgery, , Affiliated People’s Hospital of Jiangsu University, ; Zhenjiang, Jiangsu People’s Republic of China
                Article
                5040
                10.1186/s12859-022-05040-y
                9664787
                36376850
                4a292267-6867-490e-8dc7-1883eb65aa00
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 18 July 2022
                : 7 November 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100018636, Xuzhou Science and Technology Program;
                Award ID: KC19192
                Award ID: KC19192
                Award ID: KC19192
                Award ID: KC19192
                Award Recipient :
                Funded by: Xuzhou Key Research and Development Project
                Award ID: KC20124
                Award ID: KC20124
                Award ID: KC20124
                Award ID: KC20124
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Bioinformatics & Computational biology
                hepatocellular carcinoma,recurrence,prognosis
                Bioinformatics & Computational biology
                hepatocellular carcinoma, recurrence, prognosis

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