Dataset Information

Identification of Prognostic Biomarkers for Suppressing Tumorigenesis and Metastasis of Hepatocellular Carcinoma through Transcriptome Analysis.

ABSTRACT: Cancer is one of the deadliest diseases developed through tumorigenesis and could be fatal if it reaches the metastatic phase. The novelty of the present investigation is to explore the prognostic biomarkers in hepatocellular carcinoma (HCC) that could develop glioblastoma multiforme (GBM) due to metastasis. The analysis was conducted using RNA-seq datasets for both HCC (PRJNA494560 and PRJNA347513) and GBM (PRJNA494560 and PRJNA414787) from Gene Expression Omnibus (GEO). This study identified 13 hub genes found to be overexpressed in both GBM and HCC. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability, leading to improper chromosome segregation, causing aneuploidy. A 13-gene predictive model was obtained and validated using a KM plot. These hub genes could be prognostic biomarkers and potential therapeutic targets, inhibition of which could suppress tumorigenesis and metastasis.

SUBMITTER: Mishra D

PROVIDER: S-EPMC10001411 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Identification of Prognostic Biomarkers for Suppressing Tumorigenesis and Metastasis of Hepatocellular Carcinoma through Transcriptome Analysis.

Mishra Divya D Mishra Ashish A Rai Sachchida Nand SN Vamanu Emanuel E Singh Mohan P MP

Diagnostics (Basel, Switzerland) 20230303 5

Cancer is one of the deadliest diseases developed through tumorigenesis and could be fatal if it reaches the metastatic phase. The novelty of the present investigation is to explore the prognostic biomarkers in hepatocellular carcinoma (HCC) that could develop glioblastoma multiforme (GBM) due to metastasis. The analysis was conducted using RNA-seq datasets for both HCC (PRJNA494560 and PRJNA347513) and GBM (PRJNA494560 and PRJNA414787) from Gene Expression Omnibus (GEO). This study identified 1 ...[more]

PMID: 36900109

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Project description:BackgroundHepatocellular carcinoma (HCC) most commonly develops in patients who have a viral infection, especially in the case of hepatitis B virus (HBV), and in patients with a chronic liver disease. HCC patients with bone metastasis (BM) suffer from pain and other symptoms that significantly reduce their quality of life. Identification of patients who are at high risk for BM after undergoing potentially curative treatment for HCC remains challenging. Here, we aimed to identify HCC BM-related genes and proteins to establish prediction biomarkers.MethodsRNA was extracted from 48 pairs of intratumoral and peritumoral formalin-fixed, paraffin-embedded tissue from HCC patients with and without BM. A cDNA-mediated annealing, selection, extension and ligation assay containing 502 cancer-related genes was used to identify novel BM-associated genes. An additional independent study with 350 HCC patients who had undergone hepatectomy was conducted to evaluate the expression of candidate genes at the protein level using immunohistochemistry on tissue microarrays (TMAs). Of the 350 patients, 273 (78.0%) were infected with HBV.ResultsSeven intratumoral genes and 17 peritumoral genes were overexpressed in patients with BM, whereas 15 intratumoral genes and 28 peritumoral genes were underexpressed in patients with BM. We selected the following four genes for further analysis because they were differentially expressed in the cancer gene-specific microarray and were previously reported to be associated with BM: connective tissue growth factor (CTGF), matrix metalloproteinase-1 (MMP-1), transforming growth factor β1 (TGF-β1), and interleukin-11 (IL-11). We assessed the protein expression of these selected genes using immunohistochemistry on TMAs including 350 HCC patient specimens. We determined that expression of intratumoral CTGF, intratumoral IL-11, and peritumoral MMP-1 were independent prognostic factors for developing BM in HCC patients. Combining intratumoral CTGF and IL-11 expression was also an independent risk factor for BM development.ConclusionsSixty-seven genes were differentially expressed in HCC patients with and without BM. High intratumoral CTGF, positive IL-11, and high peritumoral MMP-1 expression were associated with BM after hepatectomy. Intratumoral CTGF expression combined with IL-11 expression may serve as a useful predictive biomarker for HCC BM.

Dataset Information

Identification of Prognostic Biomarkers for Suppressing Tumorigenesis and Metastasis of Hepatocellular Carcinoma through Transcriptome Analysis.

Publications

Identification of Prognostic Biomarkers for Suppressing Tumorigenesis and Metastasis of Hepatocellular Carcinoma through Transcriptome Analysis.

Similar Datasets

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