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

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.

Zhao YC ，Wang TJ ，She LZ ，Cui J ，Zhang CH ... -  《Journal of Cancer》

SERPINB7 as a prognostic biomarker in cervical cancer: Association with immune infiltration and facilitation of the malignant phenotype.

Wei HF ，Zhang RF ，Zhao YC ，Tong XS ... -  《Heliyon》

TPM3: a novel prognostic biomarker of cervical cancer that correlates with immune infiltration and promotes malignant behavior in vivo and in vitro.

Zhao YC ，Wang TJ ，Qu GH ，She LZ ，Cui J ，Zhang RF ，Qu HD ... -  《American Journal of Cancer Research》

The role of SLC39A4 in the prognosis, immune microenvironment, and contribution to malignant behavior in vivo and in vitro of cervical cancer.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are becoming more common in younger women. Solute carrier family 39 member 4 (SLC39A4) produces a zinc ion transporter involved in metastasis and invasion of tumors. The Cancer Genome Atlas RNA-seq data was used to investigate the expression of SLC39A4 and its prognostic potential. The assessment of the effect of SLC39A4 on cell growth and migration in CESC was conducted using MTT, colony formation, and Transwell assays. SLC39A4 was studied in vivo using a xenograft mouse model, and its functional involvement in oncogenesis was investigated by identifying the associated differentially expressed genes (DEGs). We evaluated the relationships among SLC39A4 levels, chemosensitivity, radiosensitivity and immune infiltration. SLC39A4 was upregulated in CESC samples, and individuals with greater SLC39A4 mRNA expression had shorter overall survival. SLC39A4 has been identified to be a regulator of tumor cell metastasis and proliferation in vivo and in vitro, with an area under the curve of 0.874 for diagnosing CESC. In total, 948 DEGs were discovered to be enriched in key CESC progression-related signaling pathways. Additionally, intratumoral immune checkpoint and infiltration activity were associated with SLC39A4 expression. High SLC39A4 expression exhibited poor chemosensitivity and radiosensitivity profiles. In conclusion, SLC39A4 is a key regulator of CESC development, prognosis, and the composition of the tumor immune microenvironment. SLC39A4 could be used as a prognostic or diagnostic screening tool and as a potential target for CESC treatment.

Zhao YC ，Wang TJ ，Cui J ，She LZ ，Zhang RF ，Zhang CH ... -  《Translational Oncology》

SQLE-a promising prognostic biomarker in cervical cancer: implications for tumor malignant behavior, cholesterol synthesis, epithelial-mesenchymal transition, and immune infiltration.

Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development. RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed. SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis. SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.

Zhao YC ，Li YF ，Qiu L ，Jin SZ ，Shen YN ，Zhang CH ，Cui J ，Wang TJ ... -  《BMC CANCER》