A Systematic Pan-Cancer Analysis and Experimental Verification Reveals SPATS2L as a Potential New Immunological and Prognostic Biomarker of Lung adenocarcinoma

Abstract

Abstract Background SPATS2L (Spermatogenesis-associated serine-rich 2-like) is an intranuclear stress-response protein involved in chromosomal organization, ribosomal biogenesis, and translational control. Although there is mounting evidence that SPATS2L was involved in the carcinogenesis of some cancers, no thorough pan-cancer investigation of SPATS2L is available so far. Results Based on multiple databases, including TCGA, GTEx, CCLE, cBioPortal, TIMER2, ImmuCellAI, GDSC, and Reactome, we analyzed the expression, prognosis, DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), immune cell infiltration, drug sensitivity, and clinicopathological and prognostic relevance of SPATS2L in pan-cancer including 33 types of cancers. Lung adenocarcinoma (LUAD) specimens were enrolled to test the expression of SPATS2L by immunohistochemistry. LUAD cell A549 transfected with siRNA targeting SPATS2L was used in subsequent experiments. SPATS2L expression was dramatically increased in a variety of malignancies, while it was low in ACC, KICH, and LAML as indicated by multiple databases and confirmed by immunohistochemistry assays. Importantly, SPATS2L has been found to have prognostic and clinicopathological importance in several malignancies. SPATS2L expression was also linked to TMB and MSI in 9 types of cancers, and there was a link between SPATS2L expression and DNA methylation in 28 types of cancers. SPATS2L was also found to be highly linked with immune cell infiltration, ICP expression, stromal score, immune score, and ESTIMATE score in various malignancies, demonstrating their regulatory roles on the TME. Consistently, the results of GSEA and GSVA analyses revealed a substantial link between SPATS2L and certain cellular immunological responses. SPATS2L was found to be strongly linked to 173 anti-tumor drugs. The overexpressed SPATS2L in LUAD tissues was validated. Knockdown of SPATS2L inhibited LUAD cell proliferation and promoted apoptosis. Conclusions This study indicated that SPATS2L might be a potential cancer biomarker for the prognosis and immunotherapeutic response. SPATS2L expression in cancers may be involved in the regulation of the tumor immune microenvironment and drug sensitivity, which may be a new-targeted molecule for developing anti-tumor drugs and immunotherapy, especially for LUAD.