Chemokines have been reported to be involved in tumorigenesis and progression and can also modulate the tumor microenvironment. However, it is still unclear whether chemokine-related long noncoding RNAs (lncRNAs) can affect the prognosis of colon adenocarcinoma (COAD). We summarized chemokine-related genes and downloaded RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) database. A total of 52 prognostic chemokine-related lncRNAs were screened by univariate Cox regression analysis; patients were grouped according to cluster analysis results. Lasso regression analysis was applied to determine chemokine-related lncRNAs to construct a risk model for further research. This study first investigated the differences between the prognosis and immune status of two chemokine-related lncRNAs clusters by consensus clustering. Then, using various algorithms, we obtained ten chemokine-related lncRNAs to construct a new prognostic chemokine-related lncRNAs risk model. The risk model's predictive efficiency, validity, and accuracy were further validated and determined in the test and training cohorts. Furthermore, this risk model played a vital role in predicting immune cell infiltration, immune checkpoint gene expression, tumor mutational burden (TMB), immunotherapy score, and drug sensitivity in COAD patients. These findings elucidated the critical role of novel prognostic chemokine-related lncRNAs in prognosis, immune landscape, and drug therapy, thereby providing valuable insights for prognosis assessment and personalized treatment strategies for COAD patients.
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