Construction of a Prognostic Model for Predicting Colorectal Cancer Prognosis and Response to Immunotherapy Based on Cuproptosis-Associated lncRNAs

Abstract

Colorectal cancer (CRC) is a common and highly lethal gastrointestinal malignancy. Immunotherapy has shown positive efficacy in the treatment of CRC; however, only a minority of patients benefit from immunotherapy. The aim of this study is to construct a cuproptosis-related lncRNA (CRLs) risk score model to predict the prognosis and immune infiltration of CRC patients. Firstly, we synthetically analyzed 19 cuproptosis-related genes (CRGs) from CRC samples derived from the TCGA and obtained 33 CRLs that were significantly associated with prognosis. Next, we defined three cuproptosis modification patterns via consensus clustering analysis (C1, C2, and C3). Further analysis showed that there were significant differences in the abundance of B cells, NK cells, fibroblasts, monocytes, CD8+ cells, bone marrow dendritic cells, and cytotoxic lymphocytes in different clusters. In addition, the LASSO regression screened out 6 individual CRLs (AC009315.1, PLS3-AS1, ZEB1-AS1, AC007608.3, AC010789.2, and AC010207.1) closely related to the prognosis of CRC. We found that the low-risk group had better survival prognoses in patients. Furthermore, the high-risk group had lower immune scores and exhibited lower CD8+ T cell infiltration. Moreover, the low-risk group had lower immune exclusion, immune dysfunction and TIDE scores than the high-risk group. Interestingly, the lncRNAs in our risk model were positively associated with most immune checkpoints. CD274 (PD-L1), CTLA4, and HAVCR2 (TIM3) were positively correlated with risk scores. Moreover, MSI-H patients had lower risk scores than MSI-L patients, and IPS scores were significantly higher in the low CRLs score group. In conclusion, we constructed a novel risk score model with6 lncRNAs related to cuproptosis, which may be a potential biomarker for evaluating the prognosis and immune treatment for CRC.

Construction and validation of eight cuproptosis-related lncRNAs signature for predicting prognosis and immune response in melanoma

“…There is other study that has also observed reduced tumorin ltrating CD8 + T cell values in SKCM patients [49]. This study's results on immune in ltration analysis align with those of Yang et al, who found decreased CD8 + T-cell in ltration of the high risk group in colorectal cancer patients [50].…”

Relationships of SIGLEC family-related lncRNAs with clinical prognosis and tumor immune microenvironment in ovarian cancer

“…A six SIGLEC family-related lncRNAs prognostic signature (AC007608.3, AC008750.1, AC039056.2, AC078788.1, AL021878.2, AL133279.1) was established to predict the OS of OC patients and all of them have close correction with worse prognosis of OC. Previous research has shown that AC007608.3 was related to cuproptosis and poor prognosis of colorectal cancer 23 . Feng et al 24 revealed that AC078788.1 was associated with tumor immunity and a favorable prognosis of OC.…”

“…We calculated the correlation coefficient between 15 SIGLEC family genes and lncRNAs based on Pearson correlation analysis. Then, SIGLEC family-related lncRNAs were selected out acrroding to the screening criteria p < 0.05 and |R|> 0.4 23 .…”