The prognostic importance of the negative regulators of ferroptosis, GPX4 and HSPB1, in patients with colorectal cancer
- Tadanobu Shimura 1, Chengzeng Yin 1, Ruiya Ma 1,2, Aiying Zhang 1, Yuka Nagai 1, Aoi Shiratori 1, Hana Ozaki 1, Shinji Yamashita 1, Koki Higashi 1, Yuki Sato 1, Hiroki Imaoka 1, Takahito Kitajima 1,3, Mikio Kawamura 1, Yuhki Koike 1, Yoshiki Okita 1, Shigeyuki Yoshiyama 1, Masaki Ohi 1, Akinobu Hayashi 4, Hiroshi Imai 4, Xueming Zhang 2, Yoshinaga Okugawa 1,3, Yuji Toiyama 1
- Tadanobu Shimura 1, Chengzeng Yin 1, Ruiya Ma 1,2
- 1Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
- 2Department of Surgery, Tangshan Gongren Hospital, Tangshan, Hebei 063007, P.R. China.
- 3Department of Genomic Medicine, Mie University Hospital, Tsu, Mie 514-8507, Japan.
- 4Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
- 0Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
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View abstract on PubMed
Summary
This summary is machine-generated.Negative regulators of ferroptosis, specifically glutathione peroxidase 4 (GPX4) and heat shock protein β-1 (HSPB1), are poor prognostic markers in colorectal cancer (CRC). High expression of GPX4 and HSPB1 predicts worse survival and recurrence in CRC patients.
Area Of Science
- Biochemistry
- Oncology
- Molecular Biology
Background
- The prognostic significance of ferroptosis regulators in colorectal cancer (CRC) remains incompletely understood.
- Ferroptosis, a regulated form of cell death, is implicated in cancer progression and treatment response.
Purpose Of The Study
- To systematically identify and validate negative regulators of ferroptosis as prognostic biomarkers in colorectal cancer.
- To investigate the role of identified regulators in chemoresistance.
Main Methods
- <i>In silico</i> analysis of The Cancer Genome Atlas (TCGA) data for ferroptosis regulators.
- Clinical validation using immunohistochemistry on CRC patient samples (n=166).
- <i>In vitro</i> experiments with small interfering RNAs (siRNAs) in CRC cell lines.
Main Results
- <i>In silico</i> analysis identified GPX4 and HSPB1 as key candidate negative regulators.
- High GPX4 and HSPB1 expression correlated with significantly worse overall survival (OS) and recurrence-free survival (RFS) in CRC patients (P<0.01).
- GPX4 and HSPB1 knockdown attenuated the cytotoxic effect of 5-fluorouracil chemotherapy in CRC cell lines.
Conclusions
- Glutathione peroxidase 4 (GPX4) and heat shock protein β-1 (HSPB1) are significant prognostic and recurrence-predictive biomarkers in colorectal cancer.
- GPX4 and HSPB1 may play a role in chemoresistance, suggesting potential therapeutic targets.
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