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

Abstract

BackgroundGastric 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.MethodsThe 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.ResultsThe 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.ConclusionThe 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.

Identification of a DNA damage repair-related LncRNA signature for predicting the prognosis and immunotherapy response of hepatocellular carcinoma

“…The dysfunction of the DDR process has been determined to have important implications for carcinogenesis, progression, treatment and prognosis in HCC. In previous studies, the DDR-related lncRNAs signature for prognostic prediction have been described in many kinds of cancers, such as gastric cancer [ 15 ], colon cancer [ 16 ], ovarian cancer [ 17 ], etc. However, the DDR-related lncRNAs in the HCC prognostic model remains to be clarified.…”

Establishment and validation of a prognostic scoring model based on disulfidptosis-related long non-coding RNAs in stomach adenocarcinoma

“…STAD, a malignant tumour, is highly prevalent worldwide and has a poor prognosis ( 22 ). Research has demonstrated that lncRNA plays a regulatory role in the progression of gastric cancer, making it a promising target for the treatment of cancers ( 23 , 24 ). Lin et al identified lncRNA BC002811 as a promoter of gastric cancer metastasis through decoying SOX2 and inhibiting PTEN transcription ( 25 ).…”