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. 2022 Jan 4:12:705512.
doi: 10.3389/fgene.2021.705512. eCollection 2021.

INHBA is a Prognostic Biomarker and Correlated With Immune Cell Infiltration in Cervical Cancer

Kaidi Zhao  1 , Yuexiong Yi  1 , Zhou Ma  1 , Wei Zhang  1
Affiliations

INHBA is a Prognostic Biomarker and Correlated With Immune Cell Infiltration in Cervical Cancer

Kaidi Zhao et al. Front Genet. .

Abstract

Background: Inhibin A (INHBA), a member of the TGF-β superfamily, has been shown to be differentially expressed in various cancer types and is associated with prognosis. However, its role in cervical cancer remains unclear. Methods: We aimed to demonstrate the relationship between INHBA expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. Next, we validated INHBA expression in cervical cancer using the Gene Expression Omnibus (GEO) database, including GSE7803, GSE63514, and GSE9750 datasets. Enrichment analysis of INHBA was performed using the R package "clusterProfiler." We analyzed the association between immune infiltration level and INHBA expression in cervical cancer using the single-sample gene set enrichment analysis (ssGSEA) method by the R package GSVA. We explored the association between INHBA expression and prognosis using the R package "survival". Results: Pan-cancer data analysis showed that INHBA expression was elevated in 19 tumor types, including cervical cancer. We further confirmed that INHBA expression was higher in cervical cancer samples from GEO database and cervical cancer cell lines than in normal cervical cells. Survival prognosis analysis indicated that higher INHBA expression was significantly associated with reduced Overall Survival (p = 0.001), disease Specific Survival (p = 0.006), and Progression Free Interval (p = 0.001) in cervical cancer and poorer prognosis in other tumors. GSEA and infiltration analysis showed that INHBA expression was significantly associated with tumor progression and some types of immune infiltrating cells. Conclusion: INHBA was highly expressed in cervical cancer and was significantly associated with poor prognosis. Meanwhile, it was correlated with immune cell infiltration and could be used as a promising prognostic target for cervical cancer.

Keywords: INHBA; biomarker; cervical cancer; immune infiltration; prognosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
INHBA expression level analysis in pan-cancer. (A) INHBA expression in normal and tumor tissues in TCGA and GTEx data. (B) Boxplot representation of INHBA expression in cervical cancer tissue. (C–E) INHBA expression in normal cervical tissues and cervical cancer epithelial component from GSE7803, GSE9750 and GSE63514. (F) qRT-PCR analysis of INHBA expression in the indicated cell lines.
FIGURE 2
FIGURE 2
Top 10 INHBA-binding proteins obtained by STRING database.
FIGURE 3
FIGURE 3
Significant Gene Ontology terms of the top 100 genes most positively associated with INHBA, including BP (biological processes), MF (molecular function) and CC (cell component).
FIGURE 4
FIGURE 4
Significant KEGG pathway of the top 100 genes most positively associated with INHBA.
FIGURE 5
FIGURE 5
Top 9 significant results most positively associated with INHBA, including Reactome pathways and KEGG pathways.
FIGURE 6
FIGURE 6
Association between INHBA expression and cancer survival prognosis. (A) CESC INHBA OS Survival. (B) CESC INHBA DSS Survival. (C) CESC INHBA PFI Survival. (D) HNSC INHBA OS Survival. (E) STAD INHBA OS Survival. (F) BRCA INHBA DSS Survival. (G) HNSC INHBA DSS Survival. (H) BRCA INHBA PFI Survival. (I) DLBC INHBA PFI Survival. (J) HNSC INHBA PFI Survival.
FIGURE 7
FIGURE 7
The correlation between INHBA expression level and 24 immune cell types. The size of dots indicate the absolute value of Spearman r.
FIGURE 8
FIGURE 8
Immune cells postively correlated with INHBA expression. (A) Correlation between INHBA expression and Macrophages. (B) Correlation between INHBA expression and Mast cells. (C) Correlation between INHBA expression and NK cells. (D) Correlation between INHBA expression and Neutrophils. (E) Correlation between INHBA expression and Th2 cells. (F) Correlation between INHBA expression and Eosinophils.
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