The Association of EGFL7 Polymorphism and Expression with Cervical Cancer Susceptibility and Pathogenesis

Weipeng Liu,1,2,* Zhixin Niu,1,* Zhiling Yan,3 Lei Shi,1 Shao Zhang,3 Chao Hong,1 Shuying Dai,4 Li Shi,1 Yufeng Yao1 1Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People’s Republic of China; 2Department of Orthopedics, The First People’s Hospital of Yunnan Province, Kunming University of Science and Technology Affliated Hospital; the Key Laboratory of Digital Orthopedics of Yunnan Province; the Clinical Medicine Center of Spinal and Spinal Cord Disorders of Yunnan Province, Kunming, People’s Republic of China; 3Department of Gynaecologic Oncology, No.3 Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Department of Pathogen Biology and Immunology Faculty of Basic Medical Science, Kunming Medical University, Kunming, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Shi; Yufeng Yao, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People’s Republic of China, Email [email protected]; [email protected]: Previous studies have highlighted diverse roles for EGFL7 in various cancers, but its specific function in cervical cancer remains unclear. This study aimed to elucidate the role of EGFL7 in cervical cancer susceptibility and pathogenesis.Methods: We genotyped three EGFL7 SNPs in 694 healthy controls, 408 cervical intraepithelial neoplasia (CIN) patients, and 934 cervical cancer (CC) patients using TaqMan probe-based real-time PCR. EGFL7 expression was measured in tumor tissues and cell lines via qRT-PCR. RNA sequencing was used to explore the biological functions of EGFL7 in cervical cancer.Results: The G allele frequency of rs9411260 was significantly elevated in both the cervical cancer (CC) (P = 0.006) and cervical intraepithelial neoplasia (CIN) (P = 0.016) groups compared to the control group. EGFL7 mRNA expression was markedly downregulated in cervical cancer tissues and HeLa/C33A cells compared to normal tissues and ECT1/E6E7 cells. Furthermore, modulation of EGFL7 expression was found to alter pathways associated with cell adhesion, migration, and ECM-receptor interaction.Conclusion: EGFL7 polymorphisms and expression are associated with cervical cancer susceptibility. Dysregulated EGFL7 appears to contribute to cervical cancer progression by affecting cell adhesion and migration, offering new insights into its pathogenesis and potential therapeutic targets.Keywords: EGFL7, SNPs, cervical cancer, cell adhesion, migration