A chemoresistance lncRNA signature for recurrence risk stratification of colon cancer patients with chemotherapy

Abstract

Chemotherapy is considered the nonsurgical treatment of choice for colon cancer patients. However, no precise molecular markers are available to determine which patients can actually benefit from it. In this study, we identified 55 chemotherapy-specific long non-coding RNAs (lncRNAs) of colon cancer patients through a systematic assessment of lncRNA expression profiles from a public database. These were taken from multiple cohorts of colon cancer patients who had received chemotherapy, or not. Based on these data, a chemoresistance lncRNA signature, named CRLSig, was constructed and successfully applied to divide chemotherapy patients into two groups with different recurrence-free survival (RFS) rates. Gene set enrichment analysis revealed that patients with low CRLSig had more infiltrating CD8+ T cells and macrophages, while those with high CRLSig had more infiltrating natural killer T cells. KEGG pathway analysis revealed that the low CRLSig group had more activated metabolic pathways compared with those in the high CRLSig group, indicating better response to chemotherapy. Single-cell sequencing analysis revealed that stromal cells and epithelial cells had higher CRLSig. Thus, we have constructed an auxiliary prognostic tool, CRLSig, able to discriminate patients at high risk of RFS, despite having received standard adjuvant chemotherapy treatment.

Graphical Abstract

Highlights

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  A CRLSig was constructed for the first time

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  CRLSig revealed chemotherapy patients with different RFS rates

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  Low CRLSig group had more activated metabolic pathways

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  ScRNA-seq analysis revealed stromal cells and epithelial cells had higher CRLSig