Identification and validation of an immunotherapeutic signature for colon cancer based on the regulatory patterns of ferroptosis and their association with the tumor microenvironment

Liu，Yong1,2; Zhao，Junzhang3; Huang，Baoxiang1,2; Liang，Youcheng4; Jiang，Guanming5; Zhou，Xinglin1,2; Chen，Yilin1,2; He，Tao6; Zheng，Mingbin2,7; Huang，Zunnan1,2

2024-04-01

10.1016/j.bbamcr.2024.119698

Biochimica et Biophysica Acta - Molecular Cell Research   影响因子和分区

0167-4889

1879-2596

The integrated landscape of ferroptosis regulatory patterns and their association with colon microenvironment have been demonstrated in recent studies. However, the ferroptosis-related immunotherapeutic signature for colon cancer (CC) remains unclear. We comprehensively evaluated 1623 CC samples, identified patterns of ferroptosis modification based on ferroptosis-associated genes, and systematically correlated these patterns with tumor microenvironment (TME) cell infiltration characteristics. In addition, the ferroptosis-regulated gene score (FRG-score) was constructed to quantify the pattern of ferroptosis alterations in individual tumors. Three distinct patterns of ferroptosis modification were identified, including antioxidant defense, iron toxicity, and lipid peroxidation. The characteristics of TME cell infiltration under these three patterns were highly consistent with the three immune phenotypes of tumors, including immune-inflamed, immune-excluded and immune-desert phenotypes. We also demonstrated that evaluation of ferroptosis regulatory patterns within individual tumors can predict tumor inflammatory status, tumor subtype, TME stromal activity, genetic variation, and clinical outcome. Immunotherapy cohorts confirmed that patients with low FRG-scores showed remarkable therapeutic and clinical benefits. Furthermore, the hub gene apolipoprotein L6 (APOL6), a drug-sensitive target associated with cancer cell ferroptosis, was identified through our proposed novel key gene screening process and validated in CC cell lines and scRNA-seq.

APOL6 Colon cancer Drug target Ferroptosis regulation genes Immunotherapy Tumor microenvironment

SCI

英语

通讯

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85186987591

Scopus

1.Key Laboratory of Computer-Aided Drug Design of Dongguan City,The First Dongguan Affiliated Hospital,Guangdong Medical University,Dongguan,Guangdong,523710,China
2.Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University,Key Laboratory for Research and Development of Natural Drugs of Guangdong Province,School of Pharmacy,Guangdong Medical University,Dongguan,Guangdong,523808,China
3.Department of Gastroenterology,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,510655,China
4.Science and Technology Innovation Center,Guangzhou University of Chinese Medicine,Guangzhou,Guangdong,510405,China
5.Dongguan Institute of Clinical Oncology Research in Dongguan People's Hospital,Dongguan,Guangdong,523018,China
6.School of Basic Medicine,Guangdong Medical University,Dongguan,Guangdong,523018,China
7.National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,The Second Affiliated Hospital,Southern University of Science and Technology,Shenzhen,Guangdong,518112,China

Liu，Yong,Zhao，Junzhang,Huang，Baoxiang,et al. Identification and validation of an immunotherapeutic signature for colon cancer based on the regulatory patterns of ferroptosis and their association with the tumor microenvironment[J]. Biochimica et Biophysica Acta - Molecular Cell Research,2024,1871(4).

Liu，Yong.,Zhao，Junzhang.,Huang，Baoxiang.,Liang，Youcheng.,Jiang，Guanming.,...&Huang，Zunnan.(2024).Identification and validation of an immunotherapeutic signature for colon cancer based on the regulatory patterns of ferroptosis and their association with the tumor microenvironment.Biochimica et Biophysica Acta - Molecular Cell Research,1871(4).

Liu，Yong,et al."Identification and validation of an immunotherapeutic signature for colon cancer based on the regulatory patterns of ferroptosis and their association with the tumor microenvironment".Biochimica et Biophysica Acta - Molecular Cell Research 1871.4(2024).