Abstract
Ferroptosis is a newly defined mode of programmed oxidative cell death. Knowledge of ferroptosis-related long noncoding (lnc) RNA in the tumor immune microenvironment of colon cancer is lacking. We systematically analyzed the correlations between ferroptosis-related lncRNAs and the tumor microenvironment, immune cell infiltration, and patient prognosis for 379 colon cancer samples in the Cancer Genome Atlas (TCGA). Using consensus clustering, we divided the 379 colon cancer patients into two subgroups (clusters 1 and 2) based on the differentially expressed ferroptosis-related lncRNAs. Cluster 1 was preferentially associated with longer overall survival, upregulated immune checkpoint inhibitor expressions, higher immunoscores, higher stromal scores, higher estimated scores, and distinct immune cell infiltration. Cancer- and metabolism-related pathways were enriched by gene set enrichment analyses. We constructed a prognostic signature of 15 ferroptosis-related lncRNAs (ZEB1-AS1, LINC01011, AC005261.3, LINC01063, LINC02381, ELFN1-AS1, AC009283.1, LINC02361, AC105219.1, AC002310.1, AL590483.1, MIR4435-2HG, NKILA, AC021054.1, and AL450326.1) and divided the patients into the high- and low-risk-score groups. The signature was validated using TCGA training and testing cohorts. The risk signature was an independent prognostic factor for predicting survival and excellently predicted the prognoses of patients with colon cancer. Moreover, the risk signature was related to immune characteristics. Chemosensitivity analyses showed that low-risk-score patients were more sensitive to sorafenib. In summary, our work revealed the important role of ferroptosis-related lncRNAs in the tumor microenvironment and immune cell infiltration and may help determine personalized prognoses and treatment for patients with colon cancer.
Highlights
As one of the most common malignant tumors worldwide, colon cancer exhibits high morbidity and mortality, and the age of onset is becoming increasingly younger in China [1]
We found that k = 2 showed optimal clustering stability from k = 2 to k = 9 according to the cumulative distribution function (CDF) curve of the consensus score (Figure 2(a))
We evaluated the connections between risk score, clinicopathological features of 379 colon cancer patients, and expression levels of 15 ferroptosisrelated lncRNAs
Summary
As one of the most common malignant tumors worldwide, colon cancer exhibits high morbidity and mortality, and the age of onset is becoming increasingly younger in China [1]. According to Cancer Statistics, approximately 148,000 new cases of colon cancer were diagnosed in the United States in 2020, leading to more than 53,200 deaths [2]. People are being diagnosed with colon cancer at increasingly younger ages, indicating that the incidence in younger people is gradually trending upward. The precise underlying mechanisms of colon cancer and the initiation of its progression remain unclear. Ferroptosis is a newly defined mode of programmed oxidative cell death, which is distinct from other cell deaths such as apoptosis, necrosis, and autophagy. Ferroptosis is iron-dependent and Journal of Immunology Research
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