The DNA damage repair-related lncRNAs signature predicts the prognosis and immunotherapy response in gastric cancer.

BACKGROUND

Gastric cancer (GC) is one of the most prevalent cancers, and it has unsatisfactory overall treatment outcomes. DNA damage repair (DDR) is a complicated process for signal transduction that causes cancer. lncRNAs can influence the formation and incidence of cancers by influencing DDR-related mRNAs/miRNAs. A DDR-related lncRNA prognostic model is urgently needed to improve treatment strategies.

METHODS

The data of GC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. A total of 588 mRNAs involved in DDR were selected from MSigDB, 62 differentially expressed mRNAs from TCGA-STAD were obtained, and 137 lncRNAs were correlated with these mRNAs. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were used to develop a DDR-related lncRNA prognostic model. Based on the risk model, the differentially expressed gene signature A/B in the low-risk and high-risk groups of TCGA-STAD was identified for further validation.

RESULTS

The prognosis model of 5 genes (AC145285.6, MAGI2-AS3, AL590705.3, AC007405.3, and LINC00106) was constructed and classified into two risk groups. We found that GC patients with a low-risk score had a better OS than those with a high-risk score. We found that the high-risk group tended to have higher TME scores. We also found that patients in the high-risk group had a higher proportion of resting CD4 T cells, monocytes, M2 macrophages, resting dendritic cells, and resting mast cells, whereas the low-risk subgroup had a greater abundance of activated CD4 T cells, follicular helper T cells, M0 macrophages, and M1 macrophages. We observed significant differences in the T-cell exclusion score, T-cell dysfunction, MSI, and TMB between the two risk groups. In addition, we found that patients treated with immunotherapy in the low-RS score group had a longer survival and a better prognosis than those in the high-RS score group.

CONCLUSION

The prognostic model has a significant role in the TME, clinicopathological characteristics, prognosis, MSI, and drug sensitivity. We also discovered that patients treated with immunotherapy in the low-RS score group had a better prognosis. This work provides a foundation for improving the prognosis and response to immunotherapy among patients with GC.