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

• Published in: BMC cancer Vol. 24; no. 1; pp. 1133 - 21
• Main Authors: Zhao, Yue-Chen, Li, Yun-Feng, Qiu, Ling, Jin, Shun-Zi, Shen, Yan-Nan, Zhang, Chao-He, Cui, Jie, Wang, Tie-Jun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.09.2024; BioMed Central; BMC
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - immunology; Adenocarcinoma - pathology; Analysis; Animals; Antibodies; Associations, institutions, etc; Biological markers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biosynthesis; Cancer; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Cell activation; Cell culture; Cell cycle; Cell differentiation; Cell Line, Tumor; Cell Proliferation; Cell survival; Cervical cancer; Cervical carcinoma; Cervical neoplasms; Chemotherapy; Cholesterol; Cholesterol - metabolism; Cholesterol synthesis; Colorimetry; Development and progression; Diagnosis; DNA Methylation; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene set enrichment analysis; Genetic analysis; Genetic aspects; Genomics; Health aspects; Humans; Immune checkpoint; Immune infiltration; Immune response; Infiltration; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Medical prognosis; Metastases; Metastasis; Methylation; Mice; Mice, Nude; Mortality; Oncology, Experimental; Oxidoreductases; Prognosis; Proteins; Risk factors; RNA; Societies; Squalene epoxidase; Squalene epoxidase (SQLE); Squalene Monooxygenase - genetics; Squalene Monooxygenase - metabolism; Squamous cell carcinoma; Stem cells; Therapeutic targets; Tumors; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - immunology; Uterine Cervical Neoplasms - mortality; Uterine Cervical Neoplasms - pathology; Western blotting; Women; China; United States > US; Japan; Cervical neoplasms; Epithelial-mesenchymal transition; Squalene epoxidase (SQLE); Prognosis; Cholesterol synthesis; Immune infiltration
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-024-12897-0

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.