CAVIN2/SDPR Functioned as a Tumor Suppressor in Lung Adenocarcinoma from Systematic Analysis of Caveolae-Related Genes and Experimental Validation

Keyun Zhu; Baichuan Wang; Yingxi Li; Yue Yu; Zhaohui Chen; Haoran Yue; Qingxiang Meng; Dongchen Tian; Xiaofeng Liu; Weiyu Shen; Yao Tian

doi:10.7150/jca.84567

CAVIN2/SDPR Functioned as a Tumor Suppressor in Lung Adenocarcinoma from Systematic Analysis of Caveolae-Related Genes and Experimental Validation

J Cancer. 2023 Jul 3;14(11):2001-2014. doi: 10.7150/jca.84567. eCollection 2023.

Authors

Keyun Zhu¹, Baichuan Wang^{2

3}, Yingxi Li⁴, Yue Yu⁵, Zhaohui Chen⁵, Haoran Yue⁵, Qingxiang Meng⁵, Dongchen Tian⁵, Xiaofeng Liu⁵, Weiyu Shen¹, Yao Tian⁶

Affiliations

¹ Department of Thoracic Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, P. R. China, 315040.
² Anhui Medical University Clinical College of Chest, Hefei, Anhui Province, P. R. China, 230022.
³ Anhui Chest Hospital, Hefei, Anhui Province, P. R. China, 230022.
⁴ Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, P. R. China, 300070.
⁵ Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China, 300060.
⁶ Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, P. R. China, 300052.

Abstract

Background: Caveolae-Related Genes include caveolins and cavins, which are the main component of the fossa and, play important roles in a variety of physiological and pathological processes. Although increasing evidence indicated that caveolins (CAVs) and cavins (CAVINs) are involved in carcinogenesis and progression, their clinical significance and biological function in lung cancer are still limited. Methods: We investigated the expression of CAVs and CAVINs at transcriptional levels using Oncomine and Gene Expression Profiling Interactive Analysis. The protein and mRNA expression levels of CAVs and CAVINs were determined by the human protein atlas website and our surgically resected samples, respectively. The clinical value of prognostic prediction based on the expression of CAVs and CAVINs was also assessed. cBioPortal, GeneMANIA and STRING were used to analyze the molecular characteristics of CAVs and CAVINs in lung adenocarcinoma (LUAD) comprehensively. Finally, we investigated the effect of CAVIN2/SDPR (serum deprivation protein response) on LUAD cells with biological experiments in vitro. Results: The expression of CAV1/2 and CAVIN1/2/3 were significantly downregulated in LUAD and lung squamous cell carcinoma (LUSC). The patients with high expression of CAV1, CAV2, CAV3, CAVIN1 and CAVIN2/SDPR were tightly correlated with a better prognosis in LUAD, while no statistical significances in LUSC. Further, our results found that CAVIN2/SDPR can be identified as a prognostic biomarker independent of other CAVINs in patients with LUAD. Mechanically, the overexpression of CAVIN2/SDPR inhibited cell proliferation and migration owing to the cell apoptosis induction and cell cycle arrest at S phase in LUAD cells. Conclusions: CAVIN2/SDPR functioned as a tumor suppressor, and was able to serve as prognostic biomarkers in precision medicine of LUAD. Mechanically, overexpression of CAVIN2/SDPR inhibited cell proliferation by inducing cell apoptosis and S phase arrest in LUAD cells.

Keywords: LUAD; SDPR; biomarkers; cell cycle; lung cancer.