1. Department of Assisted Reproductive Centre, Zhuzhou central hospital, Xiangya hospital Zhuzhou central south university, Central South University, Zhuzhou, Hunan, China.
2. Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, Hunan, China.
3. School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China.
4. Department of Obstetrics and Gynecology, The Second Affiliated Hospital of University of South China, Hengyang, Hunan, China.
5. Medical College, Hunan Polytechnic of Environment and Biology, Hengyang, Hunan, China.
6. Department of gynecology, Clinical research center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.
7. Department of Pathology, Huizhou Sixth People's Hospital, Huizhou, Guangdong, China.
8. Department of Obstetrics and Gynecology, Foshan First People's Hospital, Foshan, Guangdong, China.
9. Center of Reproductive Medicine, The First-affiliated hospital of Hunan normal university, Hunan Provincial People's Hospital, Changsha, Hunan, China.
#These authors contributed equally to this work.
Background: Ovarian cancer (OC), a serious gynecological malignant disease, remains an enormous challenge in early diagnosis and medical treatment. Based on the GEO and TCGA databases in R language, endothelial cell-specific molecule 1 (ESM1) was confirmed separately with the bioinformatic analysis tool. ESM1 has been demonstrated to be upregulated in multiple cancer types, but the oncogenic mechanism by which ESM1 promotes OC is still largely unknown.
Methods: In this study, we used WGCNA and random survival forest variable screening to filter out ESM1 in OC differentially expressed genes (DEGs). Next, we confirmed the mRNA and protein levels of ESM1 in OC samples via PCR and IHC. The correlation between the ESM1 level and clinical data of OC patients was further confirmed, including FIGO stage, lymph node metastasis, and recurrence. The role of ESM1 in OC development was explored by several functional experiments in vivo and in vitro. Then, the molecular mechanisms of ESM1 were further elucidated by bioinformatic end experimental analysis.
Results: ESM1 was significantly upregulated in OC and was positively correlated with PFS but negatively correlated with OS. ESM1 knockdown inhibited cell proliferation, apoptosis escape, the cell cycle, angiogenesis, migration and invasion in multiple experiments. Moreover, GSVA found that ESM1 was associated with the Akt pathway, and our results supported this prediction.
Conclusion: ESM1 was closely correlated with OC development and progression, and it could be considered a novel biomarker and therapeutic target for OC patients.
Keywords: Ovarian cancer, Bioinformatic analysis, ESM1, Akt/mTOR pathway, Prognostic marker