Abstract
BackgroundCACNA1C, as a type of voltage-dependent calcium ion transmembrane channel, played regulatory roles in the development and progress of multiple tumors. This study was aimed to analyze the roles of CACNA1C in ovarian cancer (OC) of overall survival (OS) and to explore its relationships with immunity.MethodsSingle gene mRNA sequencing data and corresponding clinical information were obtained from The Cancer Genome Atlas Database (TCGA) and the International Cancer Genome Consortium (ICGC) datasets. Gene set enrichment analysis (GSEA) was used to identify CACNA1C-related signal pathways. Univariate and multivariate Cox regression analyses were applied to evaluate independent prognostic factors. Besides, associations between CACNA1C and immunity were also explored.ResultsCACNA1C had a lower expression in OC tumor tissues than in normal tissues (P < 0.001), with significant OS (P = 0.013) and a low diagnostic efficiency. We further validated the expression levels of CACNA1C in OC by means of the ICGC dataset (P = 0.01), qRT-PCR results (P < 0.001) and the HPA database. Univariate and multivariate Cox hazard regression analyses indicated that CACNA1C could be an independent risk factor of OS for OC patients (both P < 0.001). Five significant CACNA1C-related signaling pathways were identified by means of GSEA. As for genetic alteration analysis, altered CACNA1C groups were significantly associated with OS (P = 0.0169), progression-free survival (P = 0.0404), disease-free survival (P = 0.0417) and disease-specific survival (P = 9.280e-3), compared with unaltered groups in OC. Besides, CACNA1C was dramatically associated with microsatellite instability (MSI) and immunity.ConclusionsOur results shed light on that CACNA1C could be a prognostic predictor of OS in OC and it was closely related to immunity.
Highlights
Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide, with approximately 21,750 newly estimated cases and 13,940 newly estimated death in USA, 2020 [1]
The expression level of calcium voltage-gated channel subunit alpha1C (CACNA1C) in ovarian cancer (OC) based on The Cancer Genome Atlas (TCGA) and GenetypeTissue Expression (GTEx) datasets As showed in Fig. 1 A, we obtained the expression level of CACNA1C in various normal tissues and organs by GTEx database and noticed that there were significant differences between female and male in adipose tissues, breast tissues, and heart tissues
Based on OC samples from the TCGA cohort, we explored the associations between the CACNA1C expression and microsatellite instability (MSI), tumor mutational burden (TMB), tumor neoantigen burden (TNB)
Summary
Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide, with approximately 21,750 newly estimated cases and 13,940 newly estimated death in USA, 2020 [1] Despite other cancers such as endometrial cancer (EC) having higher rates of incidence, OC is the deadliest of all female reproductive cancers [2]. Bioinformatics analysis revealed that mutation of CACNA1C was significantly associated with longer overall survival (OS) in EC patients [15]. All of these indicated that CACNA1C could be served as a prognostic biomarker for human cancers. This study was aimed to analyze the roles of CACNA1C in ovarian cancer (OC) of overall survival (OS) and to explore its relationships with immunity
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