DNA damage repair-related gene signature predicts prognosis and indicates immune cell infiltration landscape in skin cutaneous melanoma

Liang, Liping; Mai, Shijie; Mai, Genghui; Chen, Ye; Liu, Le

doi:10.3389/fendo.2022.882431

Cited by 3 publications

(3 citation statements)

References 46 publications

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“…Our study found that compared with the high DDR group, the low DDR group had stronger immune cell infiltration, with immunosuppressive cells such as NK cells and M2 macrophages enriched in the high DDR group, leading to poorer prognosis, while the activated T cells and B cells were more abundant in the low DDR group, resulting in a better prognosis. Moreover, in gastric cancer and melanoma, it has also been found that patients with low DDR scores have significantly increased immune infiltration, consistent with our results ( 43 , 44 ). Studies have shown that changes in tumor DDR pathways are significantly correlated with the response to immune checkpoint inhibitors (ICIs) and can also affect patient survival ( 45 – 48 ).…”

Section: Discussionsupporting

confidence: 92%

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A novel DNA damage repair-related gene signature predicting survival, immune infiltration and drug sensitivity in cervical cancer based on single cell sequencing

et al. 2023

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BackgroundAberrant DNA damage repair (DDR) is one of the hallmarks of tumors, and therapeutic approaches targeting this feature are gaining increasing attention. This study aims to develop a signature of DDR-related genes to evaluate the prognosis of cervical cancer (CC).MethodsDifferentially expressed genes were identified between high and low DDR groups of cells from the single-cell RNA sequencing dataset GSE168652 based on DDR scores. Using the ssGSEA and WGCNA methods, DDR-related differentially expressed genes were identified from different patients within the TCGA-CESC cohort. Using Cox analysis and LASSO regression analysis, a DDR-related gene signature was constructed based on the intersection of two groups of differentially expressed genes and DDR-related genes from WGCNA, and validated in GSE52903. Immune cell infiltration analysis, mutation analysis, survival analysis, drug sensitivity analysis, etc., were performed in different groups which were established based on the DDR gene signature scoring. A key gene affecting prognosis was selected and validated through biological experiments such as wound healing, migration, invasion, and comet assays.ResultsA novel DDR-related signature was constructed and the nomogram results showed this signature performed better in predicting prognosis than other clinical features for CC. The high DDR group exhibited poorer prognosis, weaker immune cell infiltration in the immune microenvironment, lower expression of immune checkpoint-related genes, lower gene mutation frequencies and more sensitivity to drugs such as BI.2536, Bleomycin and etc. ITGB1, ZC3H13, and TOMM20 were expressed at higher levels in CaSki and HeLa cells compared to ECT1 cells. Compared with the native CaSki and HeLa cells, the proliferation, migration, invasion and DDR capabilities of CaSki and HeLa cell lines with ITGB1 suppressed expression were significantly decreased.ConclusionThe 7 DDR-related gene signature was an independent and powerful prognostic biomarker that might effectively evaluate the prognosis of CC and provide supplementary information for a more personalized evaluation and precision therapy. ITGB1 was a potential candidate gene that may affect the DDR capacity of CC cells, and its mechanism of action was worth further in-depth study.

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Section: Discussionsupporting

confidence: 92%

“…significantly increased immune infiltration, consistent with our results (43,44). Studies have shown that changes in tumor DDR pathways are significantly correlated with the response to immune checkpoint inhibitors (ICIs) and can also affect patient survival (45-48).…”

Section: Discussionsupporting

confidence: 91%

A novel DNA damage repair-related gene signature predicting survival, immune infiltration and drug sensitivity in cervical cancer based on single cell sequencing

et al. 2023

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“…The development of GC is associated with mutations in oncogenes, cancer suppressor genes, and DDRrelated genes, such as KRAS and BRCA1/2, which promote genomic instability and carcinogenesis. Based on DNA damage repair, multiple biomarkers with strong predictive effectiveness for prognosis and anticancer treatment have been identified (39)(40)(41). Nevertheless, recent research has mostly focused on the proteincoding genes involved in DDR regulation.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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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.

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Emerging prognostic biomarkers in advanced cutaneous melanoma: a literature update

Roccuzzo,

Bongiovanni,

Tonella

et al. 2024

Expert Review of Molecular Diagnostics

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DNA damage repair-related gene signature predicts prognosis and indicates immune cell infiltration landscape in skin cutaneous melanoma

Cited by 3 publications

References 46 publications

A novel DNA damage repair-related gene signature predicting survival, immune infiltration and drug sensitivity in cervical cancer based on single cell sequencing

A novel DNA damage repair-related gene signature predicting survival, immune infiltration and drug sensitivity in cervical cancer based on single cell sequencing

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

Emerging prognostic biomarkers in advanced cutaneous melanoma: a literature update

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