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Galectin-3 not Galectin-9 as a candidate prognosis marker for hepatocellular carcinoma.

ABSTRACT: Background:Galectins (Gal) are a family of protein that bind to the ?-galactoside of glycoproteins. It modulates a variety of biological functions, such as tumor growth, angiogenesis and tumor metastasis. A series of experimental and clinical evidences have been reported to support a correlation between galectin expressions and neoplastic transformation, progression and prognosis. The objective of this study was to estimate the expression of Gal-3 and Gal-9 in order to evaluate their relation to hepatocellular carcinoma (HCC) -related clinical features and their prognostic values. Methods:We evaluated Gal-3 and Gal-9 expression in 247 HCC patients by a tissue microarray immunohistochemistry method, then analyzed the relationship between expression levels of Gal-3 and Gal-9 protein and tumor parameters or clinical outcomes. Results:The Gal-3 expression was significantly higher in tumor tissues compared with adjacent non-tumor tissues (P < 0.001), while no significant differences of Gal-9 was detected (P = 0.222). A higher Gal-3 expression was significantly associated with lymph-vascular invasion (P = 0.049), poor histological differentiation (P = 0.016), and no cirrhosis (P = 0.040). In contrast, a lower Gal-9 expression was related to lymph-vascular invasion (P = 0.012) and poor histological differentiation (P = 0.002). Survival analysis showed that patients with higher Gal-3 expression had worse overall survival (P = 0.012) , however no correlation was found between Gal-9 expression and survival (P = 0.185). Multivariate analysis showed that multiple tumor (HR = 1.94, 95% CI [1.36-2.78]), tumor size ? 5 cm (HR = 1.51, 95% CI [1.07-2.12]), Lymph-vascular invasion (HR = 1.45, 95% CI [1.00-2.10]) and Gal-3 expression (HR = 1.57, 95% CI [1.06-2.33]) were independent influencing factors of prognosis in patients with hepatocellular carcinoma. Conclusion:Gal-3 was expected to serve as a novel prognostic marker of hepatocellular carcinoma, while Gal-9 expression was only related to tumor progression.

SUBMITTER: Kong F

PROVIDER: S-EPMC7501799 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Galectin-3 not Galectin-9 as a candidate prognosis marker for hepatocellular carcinoma.

Kong Fei F Jin Meishan M Cao Donghui D Jia Zhifang Z Liu Yawen Y Jiang Jing J

PeerJ 20200916

<h4>Background</h4>Galectins (Gal) are a family of protein that bind to the <i>β</i>-galactoside of glycoproteins. It modulates a variety of biological functions, such as tumor growth, angiogenesis and tumor metastasis. A series of experimental and clinical evidences have been reported to support a correlation between galectin expressions and neoplastic transformation, progression and prognosis. The objective of this study was to estimate the expression of Gal-3 and Gal-9 in order to evaluate th ...[more]

PMID: 32995093

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Project description:BackgroundHepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. PAFAH1B3 plays an important role on occurrence and development in a variety tumor. However, the function of PAFAH1B3 in HCC remains unclear.MethodsThe TIMER, ONCOMINE, Human Protein Atlas (HPA), GEPIA, The Cancer Genome Atlas (TCGA), HCCDB, UALCAN and LinkedOmics database were used to analyze the prognostic value, co-expression genes and regulator networks of PAFAH1B3 in HCC. siRNA transfections and inhibitor of PAFAH1B3 P11 were used to verify the anti-tumor effect on HCC cell lines. Gene expression was detected by qRT-PCR. The functions of PAFAH1B3 downregulation in HCC cell lines were investigated using cell cycle analysis, apoptosis detection, CCK8 assay and transwell assay. Western blot was used to evaluate the role of PAFAH1B3 on metabolic pathways in HCC cells.ResultsBased on the data from databases, the expression of PAFAH1B3 was remarkably increased in HCC patients. High expression of PAFAH1B3 was associated with poorer overall survival (OS) and disease-free survival (DFS). And PAFAH1B3 was notably linked to age, sex, grade, stage, race, and TP53 mutational status. Then, the functional network analysis showed PAFAH1B3 may be involved in HCC through cell cycle, cell metabolism, spliceosome, and RNA transport. Furthermore, the mRNA expression of PAFAH1B3 was also increased in HCC cell lines. Flow cytometry analysis showed that PAFAH1B3 manipulated apoptosis and cell cycle regulation. CCK8 assay showed that PAFAH1B3 silencing or pharmacologic inhibitor of PAFAH1B3 inhibited the proliferation of HepG2, Huh7 and MHCC-97H cells. Transwell assay results showed that PAFAH1B3 silencing also significantly impaired the invasion and migratory ability of HCC cells. In addition, PAFAH1B3 silencing significantly downregulated the expression of glycolysis and lipid synthesis signaling pathways.ConclusionOur findings suggested that PAFAH1B3 plays a critical role in progression of HCC. PAFAH1B3 as a prognosis marker and potential target for HCC has prospective clinical significance.

Project description:Background Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high mortality rate. However, spliceosomal genes are still lacking in the diagnosis and prognosis of HCC. Methods Identification of differentially expressed genes (DEGs) was performed using the limma package in R software. Modules highly related to HCC were obtained by weighted gene co-expression network analysis (WGCNA), and the module genes were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The biomarker for diagnosing HCC was determined by receiver operating characteristic (ROC) curve analysis, and the effect of the biomarker in the diagnosis of HCC was evaluated by performing five-fold cross-validation with logistic regression. HCC specimens from preoperatively treated patients were tested for biomarker by real-time quantitative polymerase chain reaction (RT-qPCR). Kaplan-Meier analysis was used to assess the relationship between biomarker and patient survival. The role of biomarker was evaluated using ESTIMATE analysis in the tumor microenvironment. Results In this study, 389 DEGs were screened out from three Gene Expression Omnibus (GEO) datasets. We also found that the turquoise module of 123 genes from The Cancer Genome Atlas (TCGA) data was the key module with the highest correlation with HCC traits. Then, 123 genes were analyzed using the KEGG enrichment pathway, and eight genes were found to be most significantly related to the spliceosome pathway. We selected 8 genes and 389 DEGs shared genes, and finally got the only gene, heterogeneous nuclear ribonucleoprotein (hnRNPU). The high expression of hnRNPU was associated with poor prognosis of HCC, and hnRNPU was a biomarker for diagnosing HCC. In the tissues of patients with excellent HCC treatment hnRNPU messenger RNA (mRNA) was lower than in the tissues of patients with poor HCC treatment. High expression of hnRNPU was significantly increased in HCC patients with low stromal (P<0.05), low immune (P<0.05), and low estimation scores (P<0.05), and with high tumor purity (P<0.05) and high malignant progression (P<0.05) of the HCC. Conclusions The hnRNPU gene identified in this study may become a new biomarker for the diagnosis and prognosis of HCC.

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Galectin-3 not Galectin-9 as a candidate prognosis marker for hepatocellular carcinoma.

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Galectin-3 not Galectin-9 as a candidate prognosis marker for hepatocellular carcinoma.

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