Abstract
Background Inhibin subunit beta B (INHBB) is a protein-coding gene that participated in the synthesis of the transforming growth factor-β (TGF-β) 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-β 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.
Highlights
Colorectal cancer (CRC) is the fourth most common cause of cancer-related death, causing at least 90,000 deaths every year, and its morbidity has increased yearly [1]
We explored the promoter methylation differences of Inhibin subunit beta B (INHBB) between colorectal cancer (CRC) and normal control and found that CRC tissue had a higher methylation level of INHBB compared to normal control in The Cancer Genome Atlas (TCGA) database (Figure 2(a))
We explored the relationship between INHBB expression and promoter methylation, and the results indicated that INHBB expression was negatively correlated with promoter
Summary
Colorectal cancer (CRC) is the fourth most common cause of cancer-related death, causing at least 90,000 deaths every year, and its morbidity has increased yearly [1]. More and more molecular mechanisms have been delineated in the tumorigenesis and metastasis of CRC, the overall survival of patients remains low, especially in stage III-IV patients [2, 3]. Kita et al indicated that high-level expression of INHBB is correlated with regional lymph node metastasis in oral cancer and promotes cell proliferation and migration [8]. The study is aimed at exploring the clinical significance of INHBB in patients with colorectal cancer (CRC) by bioinformatics analysis. 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. 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). INHBB might be a potential prognostic biomarker and a novel therapeutic target for CRC
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