KEY TAKEAWAYS
- The study aimed to identify the role of FCGR1A in OC metastasis using CRISPR/Cas9-based screening.
- FCGR1A enhanced OC metastasis via LSP1 regulation led to poor prognosis & presented a predictive factor for early postoperative metastasis.
Metastasis is a major cause of death in ovarian cancer (OC). Identifying key biomarkers can improve early postoperative detection, yet FCGR1A’s role remained unclear. The current study employed CRISPR/Cas9 screening to identify metastasis regulators.
Yingying Qi and co-workers analyzed FCGR1A and LSP1 expression in OC cell lines via qRT-PCR to identify a correlation between FCGR1A and LSP1 expression and OC metastasis.
Researchers obtained about 151 tissue samples from patients with OC, including 32 patients with metastatic cancer, with information including the TNM stage and evaluated cell migration, invasion, and proliferation using wound healing, transwell invasion, and CKK-8 assays by employing a transcription-activated library to identify potential downstream genes of FCGR1A. Further, FCGR1A expression was assessed through immunohistochemistry, and immunity risk score (IRS) scores were computed.
Results indicated that FCGR1A expression was significantly higher in OC cells vs normal ovarian cells. They found that on the downregulation of FCGR1A, a significant inhibition of metastasis was observed. Also, FCGR1A expression declined proliferation and epithelial-mesenchymal transition (EMT) progression in OC cells in vitro.
Moreover, in vivo studies demonstrated that reducing FCGR1A levels also suppressed intraperitoneal metastasis. Concurrently, decreased FCGR1A expression was associated with reduced levels of LSP1. Notably, experiments involving overexpression of LSP1 showed a partial reversal of the tumor suppressive effects observed upon FCGR1A downregulation.
Furthermore, higher FCGR1A expression levels were closely linked to increased metastasis, higher tumor grade, and stage as well as lymph node metastasis in OC. Survival analysis underscored that individuals with elevated FCGR1A expression had lower rates of tumor-free survival and overall survival compared to those with lower FCGR1A expression levels.
The study concluded that FCGR1A drives OC metastasis by regulating LSP1 and correlates with poor prognosis, favoring its potential as an early postoperative metastasis predictor.
The study received open research funds from the Sixth Affiliated Hospital of Guangzhou Medical University (202011–308), the Science and Technology Projects in Guangzhou, the Science and Technology Program of Guangzhou, China (2021–02-08–12-3017–0002), the GuangDong Basic and Applied Basic Research Foundation-Joint fund, and the Guangdong Provincial Second Hospital of Traditional Chinese Medicine Scientific Research Innovation Foundation (SEZYY2023B13).
Source: https://pubmed.ncbi.nlm.nih.gov/38879666/
Qi Y., Zhu W., Mo K., et al. (2024). “CRISPR/Cas9-based genome-wide screening for metastasis ability identifies FCGR1A regulating the metastatic process of ovarian cancer by targeting LSP1.” J Cancer Res Clin Oncol. 2024 Jun 15;150(6):306. doi: 10.1007/s00432-024-05837-9. PMID: 38879666; PMCID: PMC11180010.
