Japan Digestive Disease Week 2025
International Poster Session9 (JDDW)
October 31, 14:40–15:20, Room 15 (Kobe International Exhibition Hall No.1 Building Digital Poster Venue)
IP-45_S
Systematic identification and evaluation of ferroptosis negative regulators as potential prognostic biomarkers in colorectal cancer patients
- 1
- Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine
- 2
- Department of Genomic Medicine, Mie University
【Background】The present study performed a systematic in－silico identification and selection of candidate negative regulators of ferroptosis using The Cancer Genome Atlas data cohort （n＝367）, followed by clinical validation through immunohistochemistry of samples from colorectal cancer （CRC） patients （n＝166） and further in vitro evaluation.
【Results】In silico analysis identified SLC7A11, AIFM2, NFE2L2, FTH1, GLS2, GPX4, and HSPB1 genes as possible candidates. Furthermore, patients with high expression of GPX4 or HSPB1 exhibited significantly worse overall survival （OS）（p＜0.01 for both）. Immunohistochemical analysis revealed that both OS and recurrence free survival （RFS） of patients with CRC and high GPX4 or HSPB1 expression were significantly worse （p＜0.01 for all）. Furthermore, multivariate analysis showed that high GPX4 and HSPB1 expression were independent risk factors for poor oncological outcome for OS and RFS （GPX4： RFS, p＝0.03； HSPB1： OS, p＝0.006 and RFS, p＜0.0001）. Moreover, the effects of GPX4 and HSPB1 small interfering RNAs on two CRC cell lines （DLD－1 and SW480） indicated that GPX4 and HSPB1 may exhibit important roles in attenuating the cytotoxic effect of 5－fluorouracil based chemotherapy.
【Conclusion】The current study confirmed that GPX4 and HSPB1 may serve as substantial prognostic－ and recurrence－predictive biomarkers in patients with CRC.
【Results】In silico analysis identified SLC7A11, AIFM2, NFE2L2, FTH1, GLS2, GPX4, and HSPB1 genes as possible candidates. Furthermore, patients with high expression of GPX4 or HSPB1 exhibited significantly worse overall survival （OS）（p＜0.01 for both）. Immunohistochemical analysis revealed that both OS and recurrence free survival （RFS） of patients with CRC and high GPX4 or HSPB1 expression were significantly worse （p＜0.01 for all）. Furthermore, multivariate analysis showed that high GPX4 and HSPB1 expression were independent risk factors for poor oncological outcome for OS and RFS （GPX4： RFS, p＝0.03； HSPB1： OS, p＝0.006 and RFS, p＜0.0001）. Moreover, the effects of GPX4 and HSPB1 small interfering RNAs on two CRC cell lines （DLD－1 and SW480） indicated that GPX4 and HSPB1 may exhibit important roles in attenuating the cytotoxic effect of 5－fluorouracil based chemotherapy.
【Conclusion】The current study confirmed that GPX4 and HSPB1 may serve as substantial prognostic－ and recurrence－predictive biomarkers in patients with CRC.
- Index Term 1: colorectal cancer
- Index Term 2: ferroptosis