Abstract
Background: Signal transducing adaptor molecule 1 (STAM1) was considered to mediate cell growth and be involved in multiple signaling pathways; however, no research on the role of STAM1 in any tumors has been published yet. Our study aimed to investigate the prognostic value of STAM1 for clear cell renal cell carcinoma (ccRCC) and its role in modulating cancer cell function.Methods: Data from The Cancer Genome Atlas (TCGA) in December 2019 were used to examine the role of STAM1 in indicating ccRCC patients' survival. A purchased tissue microarray (TM) and fresh ccRCC renal tissues were used for further validation. Then, STAM1 was overexpressed in human ccRCC cell lines for in vitro assays. Finally, bioinformatics was performed for STAM1 protein–protein interaction (PPI) network construction and functional analyses.Results: A total of 539 ccRCC and 72 control samples were included for the TCGA cohort, and 149 ccRCC and 29 control slices were included for the TM cohort. In the TCGA and TM cohorts, we found that STAM1 expression was lower in ccRCC compared with normal adjacent non-cancerous renal tissues (P < 0.0001 for both cohorts). STAM1 downregulation was also related to significantly shorter overall survival (OS) (P < 0.0001 for both cohorts). In the TCGA cohort, reduced STAM1 expression was also associated with aggressive features of the tumor. Under multivariate analyses, STAM1 was demonstrated to be an independent prognostic factor for ccRCC survival in both TCGA (HR = 0.52, 95% CI: 0.33–0.84, P = 0.007) and TM cohorts (HR = 0.12, 95% CI: 0.04–0.32, P < 0.001). Our in vitro experiments showed that STAM1 inhibited cell viability, invasion, and migration in ccRCC cell lines. In PPI network, 10 candidate genes categorized into five biological processes were found to be closely related to STAM1.Conclusion: STAM1 is a promising prognostic biomarker for predicting ccRCC survival outcomes. Preliminary pathogenesis is demonstrated by our in vitro experiments. Further pathological mechanisms of STAM1 in modulating ccRCC require comprehensive laboratory and clinical studies.
Highlights
Renal cell carcinoma (RCC) is the most common kind of kidney malignant tumor
We focused on Signal transducing adaptor molecule 1 (STAM1) and its relationship with Clear cell RCC (ccRCC) by RNA sequencing through online databases at first
A ccRCC cohort from the TCGA public database was included for bioinformatic analyses, and the tissue microarray (TM) cohort was added for validation
Summary
Renal cell carcinoma (RCC) is the most common kind of kidney malignant tumor. Among more than 400,000 new cases of kidney cancer in each year, RCC is responsible for ∼90% of them [1, 2]. Clear cell RCC (ccRCC) is the most frequent histological form, accounting for 70–80% in patients bearing kidney cancer [3]. The cure rate is relatively high when the tumor is early and localized; as an aggressive subtype, the 5-year survival of ccRCC drops to < 12% when metastasis occurs [4]. For advanced ccRCC, after the patients received total nephrectomy, about 30% cases suffer from tumor recurrence [5]. Our study aimed to investigate the prognostic value of STAM1 for clear cell renal cell carcinoma (ccRCC) and its role in modulating cancer cell function
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