Dataset Information

Clinical Limitations of Tissue Annexin A2 Level as a Predictor of Postoperative Overall Survival in Patients with Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is the second common cause of cancer-related death in Taiwan. Tumor recurrence is frequently observed in HCC patients receiving surgical resection, resulting in unsatisfactory overall survival (OS). Therefore, it is pivotal to identify effective prognostic makers, so that intensive surveillance or adjuvant treatments can be applied to predictively unfavorable patients. Previous studies indicated that Annexin A2 (ANXA2) was an effective prognostic marker in several cancers, including HCC. However, the prognostic value of ANXA2 in Taiwanese HCC patients remains unclear, where a great proportion of patients had chronic hepatitis B with liver cirrhosis. Here, ANXA2 was highly expressed in HCC tissues compared with para-neoplastic noncancerous tissues. Furthermore, high ANXA2 expression in HCC tissues independently predicted shorter OS. In subgroup analysis, however, ANXA2 expression could not effectively predict OS in the following subgroups: female, age > 65 years old, Child-Pugh classification B, hepatitis B virus surface antigen negative or anti-hepatitis C antibody positive, alcoholism, tumor number >1, presence of micro- or macrovascular invasion, absence of capsule, non-cirrhosis and high alpha-fetoprotein. In conclusion, ANXA2 expression in HCC tissues could predict postoperative OS. However, the predictive value was limited in patients with specific clinical conditions.

SUBMITTER: Huang SW

PROVIDER: S-EPMC8465313 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Clinical Limitations of Tissue Annexin A2 Level as a Predictor of Postoperative Overall Survival in Patients with Hepatocellular Carcinoma.

Huang Shu-Wei SW Chen Yen-Chin YC Lin Yang-Hsiang YH Yeh Chau-Ting CT

Journal of clinical medicine 20210915 18

Hepatocellular carcinoma (HCC) is the second common cause of cancer-related death in Taiwan. Tumor recurrence is frequently observed in HCC patients receiving surgical resection, resulting in unsatisfactory overall survival (OS). Therefore, it is pivotal to identify effective prognostic makers, so that intensive surveillance or adjuvant treatments can be applied to predictively unfavorable patients. Previous studies indicated that Annexin A2 (ANXA2) was an effective prognostic marker in several ...[more]

PMID: 34575275

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Project description:BackgroundFew studies have focused on the prognosis of patients with hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage 0‒C in terms of early recurrence and 5-years overall survival (OS). We sought to develop nomograms for predicting 5-year OS and early recurrence after curative resection of HCC, based on a clinicopathological‒radiological model. We also investigated whether different treatment methods influenced the OS of patients with early recurrence.MethodsRetrospective data, including clinical pathology, radiology, and follow-up data, were collected for 494 patients with HCC who underwent hepatectomy. Nomograms estimating OS and early recurrence were constructed using multivariate Cox regression analysis, based on the random survival forest (RSF) model. We evaluated the discrimination and calibration abilities of the nomograms using concordance indices (C-index), calibration curves, and Kaplan‒Meier curves. OS curves of different treatments for patients who had recurrence within 2 years after curative surgery were depicted and compared using the Kaplan-Meier method and the log-rank test.ResultsMultivariate Cox regression revealed that BCLC stage, non-smooth margin, maximum tumor diameter, age, aspartate aminotransferase levels, microvascular invasion, and differentiation were prognostic factors for OS and were incorporated into the nomogram with good predictive performance in the training (C-index: 0.787) and testing cohorts (C-index: 0.711). A nomogram for recurrence-free survival was also developed based on four prognostic factors (BCLC stage, non-smooth margin, maximum tumor diameter, and microvascular invasion) with good predictive performance in the training (C-index: 0.717) and testing cohorts (C-index: 0.701). In comparison to the BCLC staging system, the C-index (training cohort: 0.787 vs. 0.678, 0.717 vs. 0.675; external cohort 2: 0.748 vs. 0.624, 0.729 vs. 0.587 respectively, for OS and RFS; external cohort1:0.716 vs. 0.627 for RFS, all p value<0.05), and model calibration curves all showed improved performance. Patients who underwent surgery after tumor recurrence had a higher reOS than those who underwent comprehensive treatments and supportive care.ConclusionsThe nomogram, based on clinical, pathological, and radiological factors, demonstrated good accuracy in estimating OS and recurrence, which can guide follow-up and treatment of individual patients. Reoperation may be the best option for patients with recurrence in good condition.

Project description:BackgroundLong noncoding RNAs (lncRNAs) are functionally associated with cancer development and progression. Although gene copy number variation (CNV) is common in hepatocellular carcinoma (HCC), it is not known how CNV in lncRNAs affects HCC progression and recurrence. We aimed to identify a CNV-related lncRNA involved in HCC progression and recurrence and illustrate its underlying mechanisms and prognostic value.MethodsWe analyzed the whole genome sequencing (WGS) data of matched cancerous and noncancerous liver samples from 49 patients with HCC to identify lncRNAs with CNV. The results were validated in another cohort of 238 paired HCC and nontumor samples by TaqMan copy number assay. We preformed Kaplan-Meier analysis and log-rank test to identify lncRNA CNV with prognostic value. We conducted loss- and gain-of-function studies to explore the biological functions of LINC01133 in vitro and in vivo. The competing endogenous RNAs (ceRNAs) mechanism was clarified by microRNA sequencing (miR-seq), quantitative real-time PCR (qRT-PCR), western blot, and dual-luciferase reporter assays. We confirmed the binding mechanism between lncRNA and protein by RNA pull-down, RNA immunoprecipitation, qRT-PCR, and western blot analyses.ResultsGenomic copy numbers of LINC01133 were increased in HCC, which were positively related with the elevated expression of LINC01133. Increased copy number of LINC01133 predicted the poor prognosis in HCC patients. LINC01133 overexpression in HCC cells promoted proliferation and aggressive phenotypes in vitro, and facilitated tumor growth and lung metastasis in vivo, whereas LINC01133 knockdown had the opposite effects. LINC01133 sponged miR-199a-5p, resulting in enhanced expression of SNAI1, which induced epithelial-to-mesenchymal transition (EMT) in HCC cells. In addition, LINC01133 interacted with Annexin A2 (ANXA2) to activate the ANXA2/STAT3 signaling pathway.ConclusionsLINC01133 promotes HCC progression by sponging miR-199a-5p and interacting with ANXA2. LINC01133 CNV gain is predictive of poor prognosis in patients with HCC.

Dataset Information

Clinical Limitations of Tissue Annexin A2 Level as a Predictor of Postoperative Overall Survival in Patients with Hepatocellular Carcinoma.

Publications

Clinical Limitations of Tissue Annexin A2 Level as a Predictor of Postoperative Overall Survival in Patients with Hepatocellular Carcinoma.

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