Dataset Information

INHBB Is a Novel Prognostic Biomarker Associated with Cancer-Promoting Pathways in Colorectal Cancer.

ABSTRACT: Background:Inhibin subunit beta B (INHBB) is a protein-coding gene that participated in the synthesis of the transforming growth factor-? (TGF-?) family members. The study is aimed at exploring the clinical significance of INHBB in patients with colorectal cancer (CRC) by bioinformatics analysis. Methods:Real-time PCR and analyses of Oncomine, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases were utilized to evaluate the INHBB gene transcription level of colorectal cancer (CRC) tissue. We evaluated the INHBB methylation level and the relationship between expression and methylation levels of CpG islands in CRC tissue. The corresponding clinical data were obtained to further explore the association of INHBB with clinical and survival features. In addition, Gene Set Enrichment Analysis (GSEA) was performed to explore the gene ontology and signaling pathways of INHBB involved. Results:INHBB expression was elevated in CRC tissue. Although the promoter of INHBB was hypermethylated in CRC, methylation did not ultimately correlate with the expression of INHBB. Overexpression of INHBB was significantly and positively associated with invasion depth, distant metastasis, and TNM stage. Cox regression analyses and Kaplan-Meier survival analysis indicated that high expression of INHBB was correlated with worse overall survival (OS) and disease-free survival (DFS). GSEA showed that INHBB was closely correlated with 5 cancer-promoting signaling pathways including the Hedgehog signaling pathway, ECM receptor interaction, TGF-? signaling pathway, focal adhesion, and pathway in cancer. INHBB expression significantly promoted macrophage infiltration and inhibited memory T cell, mast cell, and dendritic cell infiltration. INHBB expression was positively correlated with stromal and immune scores of CRC samples. Conclusion:INHBB might be a potential prognostic biomarker and a novel therapeutic target for CRC.

SUBMITTER: Yuan J

PROVIDER: S-EPMC7563060 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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INHBB Is a Novel Prognostic Biomarker Associated with Cancer-Promoting Pathways in Colorectal Cancer.

Yuan Jinpeng J Xie Aosi A Cao Qiangjian Q Li Xinxin X Chen Juntian J

BioMed research international 20201006

<h4>Background</h4>Inhibin subunit beta B (INHBB) is a protein-coding gene that participated in the synthesis of the transforming growth factor-<i>β</i> (TGF-<i>β</i>) family members. The study is aimed at exploring the clinical significance of INHBB in patients with colorectal cancer (CRC) by bioinformatics analysis.<h4>Methods</h4>Real-time PCR and analyses of Oncomine, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases were utilized to evaluate the INHBB gene transcri ...[more]

PMID: 33083477

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Project description:BACKGROUND:Liver cancer has a high mortality and morbidity rate throughout the world. In clinical practice, the prognosis of liver cancer patients is poor, and the complex reasons contribute to treatment failures, including fibrosis, hepatitis viral infection, drug resistance and metastasis. Thus, screening novel prognostic biomarkers is of great importance for guiding liver cancer therapy. Orosomucoid genes (ORMs) encode acute phase plasma proteins, including orosomucoid 1 (ORM1) and ORM2. Previous studies showed their upregulation upon inflammation, but the specific function of ORMs has not yet been determined, especially in the development of liver cancer. AIM:To determine the expression of ORMs and their potential function in liver cancer. METHODS:Analysis of the expression of ORMs in different human tissues was performed on data from the HPA RNA-seq normal tissues project. The expression ratio of ORMs was determined using the HCCDB database, including the ratio between liver cancer and other cancers, normal liver and other normal tissues, liver cancer and adjacent normal liver tissues. Analysis of ORM expression in different cancer types was performed using The Cancer Genome Atlas and TIMER database. The expression of ORMs in liver tumor tissues and adjacent normal tissues were further confirmed using Gene Expression Omnibus data, including GSE36376 and GSE14520. The 10-year overall survival (OS), progression-free survival (PFS) and relapse-free survival (RFS) rates between high and low ORM expression groups in liver cancer patients were determined using the Kaplan-Meier plotter tool. Gene Set Enrichment Analysis (GSEA) was employed to explore the ORM2-associated signaling network. Correlations between ORM2 expression and tumor purity or the infiltration level of macrophages in liver tumor tissues were determined using the TIMER database. The correlation between ORM2 gene levels, tumor-associated macrophage (TAM) markers (including CD68 and TGF?1) and T cell immunosuppression (including CTLA4 and PD-1) in liver tumor tissues and liver GTEx was determined using the GEPIA database. RESULTS:ORM1 and ORM2 were highly expressed in normal liver and liver tumor tissues. ORM1 and ORM2 expression was significantly decreased in liver tumor tissues compared with adjacent normal tissues, and similar results were also noted in cholangiocarcinoma, esophageal carcinoma, and lung squamous cell carcinoma. Further analysis of the Gene Expression Omnibus Database also confirmed the downregulation of ORM1 and ORM2 in liver tumors. Survival analysis showed that the high ORM2 group had better survival rates in OS, PFS and RFS. ORM1 only represented better performance in PFS, but not in OS or RFS. GSEA analysis of ORM2 from The Cancer Genome Atlas liver cancer data identified that ORM2 positively associated with the G2/M checkpoint, E2F target signaling, as well as Wnt/?-catenin and Hedgehog signaling. Moreover, apoptosis, IFN-? responses, IFN-? responses and humoral immune responses were upregulated in the ORM2 high group. ORM2 expression was negatively correlated with the macrophage infiltration level, CD68, TGF?1, CTLA4 and PD-1 levels. CONCLUSION:The results showed that ORM1 and ORM2 were highly expressed specifically in liver tissues, whereas ORM1 and ORM2 were downregulated in liver tumor tissues. ORM2 is a better prognostic factor for liver cancer. Furthermore, ORM2 is closely associated with cancer-promoting pathways.

Dataset Information

INHBB Is a Novel Prognostic Biomarker Associated with Cancer-Promoting Pathways in Colorectal Cancer.

Publications

INHBB Is a Novel Prognostic Biomarker Associated with Cancer-Promoting Pathways in Colorectal Cancer.

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