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.
Highlights
The introduction of prophylactic vaccination against human papillomavirus (HPV) and screening would substantially reduce the incidence of cervical cancer, it remains the most common gynecologic malignancy worldwide Matsuo et al (2017)
We performed pan-cancer analyses using the Mann-Whitney U test (Wilcoxon rank sum test) to compare Inhibin A (INHBA) expression in normal tissues and tumor samples using RNA sequencing data obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases (Figure 1A)
To further confirm our observations, we examined INHBA expression in cervical cancer lines, including SiHa and HeLa, compared to that in the normal epithelial cell line, END1, using qRT-PCR
Summary
The introduction of prophylactic vaccination against human papillomavirus (HPV) and screening would substantially reduce the incidence of cervical cancer, it remains the most common gynecologic malignancy worldwide Matsuo et al (2017). The global mortality rate from cervical cancer is approximately 54% Kiran et al (2018). The combination of early detection via screening and effective treatment with surgery, chemotherapy, and radiotherapy has meant that early stage cervical cancer can be successfully treated, with 5-years overall survival (OS) rates as high as 90% Potikanond et al (2017). Metastatic cervical cancer is virtually incurable, mainly due to limited treatment options, with 5-years OS rates below 10% Wallbillich et al (2020). Better prognostic biomarkers for cervical cancer development are urgently required to increase patient survival.
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