S100A10 Overexpression Correlates with Adverse Prognosis, Tumor Microenvironment, and Aggressive Behavior In Vitro and In Vivo of Cervical Cancer

Yue-Chen Zhao; Tie-Jun Wang; Li-Zhen She; Jie Cui; Chao-He Zhang

doi:10.7150/jca.87689

S100A10 Overexpression Correlates with Adverse Prognosis, Tumor Microenvironment, and Aggressive Behavior In Vitro and In Vivo of Cervical Cancer

J Cancer. 2023 Sep 11;14(15):2931-2945. doi: 10.7150/jca.87689. eCollection 2023.

Authors

Yue-Chen Zhao¹, Tie-Jun Wang¹, Li-Zhen She¹, Jie Cui¹, Chao-He Zhang²

Affiliations

¹ Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
² Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.

Abstract

Background: The incidence of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is increasing in women. S100A10 overexpression is commonly reported in various malignancies and is closely associated with tumor cell characteristics and prognosis. Methods: The expression of S100A10 and its prognostic relevance were assessed utilizing RNA-seq data from The Cancer Genome Atlas. S100A10 regulation of CESC cell growth and migration was investigated using CCK-8, colony-forming, and Transwell-based approaches. Xenograft model mice were used to examine the in vivo effects of S100A10, and differentially expressed genes (DEGs) linked to S100A10 were identified to explore its functional role in oncogenesis. Associations between S100A10 levels, chemosensitivity, and the immune microenvironment were assessed, and the mutational and methylation status of S100A10 was evaluated using the cBioPortal and MethSurv databases, respectively. Results: S100A10 was upregulated in CESC samples, and higher S100A10 mRNA levels were associated in poor prognostic outcomes. The area under the curve for S100A10 when diagnosing CESC was 0.935, and S100A10 was found to regulate tumor cell proliferation and metastasis both in vitro and in vivo. Overall, 1125 DEGs enriched in crucial CESC progression-associated signaling pathways were identified. S100A10 expression was also associated with the intratumoral immune microenvironment and immune checkpoint activity. Patients expressing elevated S100A10 levels exhibited distinct chemotherapeutic susceptibility, and methylation of the S100A10 gene was correlated with patient survival outcomes. Conclusion: In summary, this research demonstrated that S100A10 plays a crucial role in regulating CESC development, prognosis, and the intratumoral immune microenvironment. Thus, S100A10 shows potential as a prognostic or diagnostic tool and as a potential target for CESC immunotherapy.

Keywords: Cancer Biomarker; Cervical carcinoma; Prognosis; S100 Calcium Binding Protein A10 (S100A10); Tumor immune microenvironment.