Identification of Ferroptosis-Related Genes Signature Predicting the Efficiency of Invasion and Metastasis Ability in Colon Adenocarcinoma

Chunlei Shi; Yongjie Xie; Xueyang Li; Guangming Li; Weishuai Liu; Wenju Pei; Jing Liu; Xiaozhou Yu; Tong Liu

doi:10.3389/fcell.2021.815104

Identification of Ferroptosis-Related Genes Signature Predicting the Efficiency of Invasion and Metastasis Ability in Colon Adenocarcinoma

Front Cell Dev Biol. 2022 Jan 26:9:815104. doi: 10.3389/fcell.2021.815104. eCollection 2021.

Authors

Chunlei Shi^{1

2}, Yongjie Xie³, Xueyang Li^{3

4}, Guangming Li^{1

2}, Weishuai Liu^{3

5}, Wenju Pei^{1

2}, Jing Liu^{3

4}, Xiaozhou Yu^{3

6}, Tong Liu^{1

2}

Affiliations

¹ Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
² Tianjin General Surgery Institute, Tianjin, China.
³ Key Laboratory of Cancer Prevention, Department of Pancreatic Cancer, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
⁴ Department of Breast Oncoplastic Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
⁵ Department of Pain Relief, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
⁶ Department of Molecular Imaging and Nuclear Medicine, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Abstract

Background: Colon adenocarcinoma (COAD) is one of the most prevalent cancers worldwide and has become a leading cause of cancer death. Although many potential biomarkers of COAD have been screened with the bioinformatics method, it is necessary to explore novel markers for the diagnosis and appropriate individual treatments for COAD patients due to the high heterogeneity of this disease. Epithelial-to-mesenchymal transition (EMT)-mediated tumor metastasis suggests poor prognosis of cancers. Ferroptosis is involved in tumor development. EMT signaling can increase the cellular sensitivity to ferroptosis in tumors. The aim of our study is finding novel prognostic biomarkers to determine COAD patients for predicting efficiency of metastasis status and targeting precise ferroptosis-related therapy. Methods: A novel gene signature related to metastasis and ferroptosis was identified combing with risk model and WGCNA analysis with R software. The biological functions and predictive ability of the signature in COAD were explored through bioinformatics analysis. Results: We established a four-gene prognostic signature (MMP7, YAP1, PCOLCE, and HOXC11) based on EMT and ferroptosis related genes and validated the reliability and effectiveness of this model in COAD. This four-gene prognostic signature was closely connected with metastasis and ferroptosis sensitivity of COAD. Moreover, WGCNA analysis further confirmed the correlation between PCOLCE, HOXC11, and liver and lymphatic invasion of COAD. Conclusion: The four genes may become potential prognostic biomarkers to identify COAD patients with metastasis. Moreover, this four-gene signature may be able to determine the COAD suitable with ferroptosis induction therapy. Finally, PCOLCE2 and HOXC11 were selected individually because of their novelties and precise prediction ability. Overall, this signature provided novel possibilities for better prognostic evaluation of COAD patients and may be of great guiding significance for individualized treatment and clinical decision.

Keywords: COAD; HOXC11; PCOLCE; WGCNA; ferroptosis; metastasis; risk model.