Prognostic Value of Excision Repair Cross-Complementing mRNA Expression in Gastric Cancer

Luo, Shuang; Liao, Xiwen; Zhu, Xiaodong

doi:10.1155/2018/6204684

Cited by 7 publications

(4 citation statements)

References 50 publications

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“…ERCC family genes are known to play essential roles in the NER process and DNA damage repair 36 . Previous studies have suggested that ERCC genes may be involved in the tumorigenesis of various cancer types 22 , 23 . However, the relationship between ERCC genes and tumor prognosis has not been thoroughly investigated, and the association of ERCC mutations with ICI response remains uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the expression level of ERCC family genes has been linked to cancer prognosis. For example, Zhao et al discovered that the expression level of ERCC4 correlates with overall survival (OS) in ovarian and gastric cancers 22 , 23 . ERCC5 downregulation has been identified as a biomarker for ovarian cancer prognosis and a potential therapeutic target 24 .…”

Section: Introductionmentioning

confidence: 99%

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Association of ERCC family mutations with prognosis and immune checkpoint inhibitors response in multiple cancers

Chen,

Liu,

et al. 2023

Sci Rep

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The proteins encoded by the excision repair cross-complementing (ERCC) family are pivotal in DNA damage repair and maintaining genome stability. However, the precise role of the ERCC family in tumor prognosis and the effectiveness of immune checkpoint inhibitors (ICI) therapy remain uncertain. This study aimed to explore the connection between ERCC mutations and prognosis as well as the response to ICI. We observed that patients with ERCC mutations exhibited enhanced progression-free survival (PFS) and overall survival (OS) in two independent pan-cancer cohorts. Furthermore, this mutant subgroup showed higher tumor mutation burden (TMB) compared to the wild-type subgroup. Notably, ERCC mutations were associated with better OS (HR 0.54, 95% CI 0.42–0.70; P < 0.001) in pan-cancer patients who underwent ICI therapy (N = 1661). These findings were validated in a separate cohort, where patients in the ERCC mutant subgroup demonstrated improved clinical outcomes (HR 0.56, 95% CI 0.37–0.84; P = 0.03) and higher response rates (51.9% vs. 26.8%) than the wild-type subgroup. Further analysis revealed that patients with ERCC mutations displayed elevated tumor neoantigen burden (TNB) levels and increased infiltration of immune-response cells. Our study suggests that ERCC mutations are linked to enhanced immunogenicity and improved ICI efficacy, thus potentially serving as a biomarker for ICI therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of ERCC family mutations with prognosis and immune checkpoint inhibitors response in multiple cancers

Chen,

Liu,

et al. 2023

Sci Rep

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“…RAD23B, DDB1, and ERCC family genes (ERCC1, ERCC5, and ERCC6) are key genes in the NER pathway. Many studies have reported that they are significantly correlated with prognosis in different cancer types, such as colorectal cancer, pancreatic cancer, gastric cancer, and so on ( Luo et al, 2018 ; Zhang et al, 2019 ; Li et al, 2021 ). NEIL3 , PCNA , RFC3 , and POLD2 play important roles in the BER pathway which are recruited to DNA lesions and cleave and repair the damaged bases cooperatively ( Robertson et al, 2009 ; Hurst et al, 2021 ; Wang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

DNA Damage Response Gene-Based Subtypes Associated With Clinical Outcomes in Early-Stage Lung Adenocarcinoma

Zhao

Qing

et al. 2022

Front. Mol. Biosci.

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DNA damage response (DDR) pathways play a crucial role in lung cancer. In this retrospective analysis, we aimed to develop a prognostic model and molecular subtype based on the expression profiles of DDR-related genes in early-stage lung adenocarcinoma (LUAD). A total of 1,785 lung adenocarcinoma samples from one RNA-seq dataset of The Cancer Genome Atlas (TCGA) and six microarray datasets of Gene Expression Omnibus (GEO) were included in the analysis. In the TCGA dataset, a DNA damage response gene (DRG)–based signature consisting of 16 genes was constructed to predict the clinical outcomes of LUAD patients. Patients in the low-DRG score group had better outcomes and lower genomic instability. Then, the same 16 genes were used to develop DRG-based molecular subtypes in the TCGA dataset to stratify early-stage LUAD into two subtypes (DRG1 and DRG2) which had significant differences in clinical outcomes. The Kappa test showed good consistency between molecular subtype and DRG (K = 0.61, p < 0.001). The DRG subtypes were significantly associated with prognosis in the six GEO datasets (pooled estimates of hazard ratio, OS: 0.48 (0.41–0.57), p < 0.01; DFS: 0.50 (0.41–0.62), p < 0.01). Furthermore, patients in the DRG2 group benefited more from adjuvant therapy than standard-of-care, which was not observed in the DRG1 group. In summary, we constructed a DRG-based molecular subtype that had the potential to predict the prognosis of early-stage LUAD and guide the selection of adjuvant therapy for early-stage LUAD patients.

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“…For example, Zhao et al ( 32 ) reported that high expression of ERCC6 was associated with poor OS in patients with colorectal cancer who received or did not receive treatment with 5-fluorouracil. Luo et al ( 33 ) revealed that ERCC6 may be a biomarker for the prognosis of gastric cancer. Pu et al ( 34 ) demonstrated that the expression of ERCC6L was significantly correlated with the clinical survival of patients with breast and gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of ERCC6L correlates with poor prognosis and confers malignant phenotypes of lung adenocarcinoma

et al. 2022

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Excision repair cross-complementation group 6 like (ERCC6L) has been reported to be upregulated in a variety of malignant tumors and plays a critical oncogenic role. However, the role and molecular mechanism of ERCC6L in lung adenocarcinoma (LUAD) remain unclear, and were therefore investigated in the present study. Clinical data of patients with LUAD were obtained and bioinformatics analysis was performed to investigate the expression characteristics, prognostic value, and biological function of ERCC6L. In addition, cell function experiments were performed to detect the effect of ERCC6L silencing on the biological behavior of LUAD cells. The results revealed that ERCC6L expression was significantly higher in LUAD tissues vs. normal lung tissues and closely associated with nodal invasion, advanced clinical stage and survival in LUAD. Overexpression of ERCC6L was an independent prognostic biomarker of overall survival, progression-free interval, and disease-specific survival in patients with LUAD. DNA amplification and low methylation levels of ERCC6L suggested regulation at both the genetic and epigenetic levels. The most significant positive genes co-expressed with ERCC6L were mainly enriched in the cell cycle signaling pathway. The major functions of ERCC6L in LUAD cells were positively correlated with the cell cycle, DNA damage, DNA repair, proliferation, invasion and epithelial-mesenchymal transition (EMT). Knockdown of ERCC6L inhibited the proliferative, migratory and invasive abilities of A549 and PC9 cells. It also promoted cell apoptosis, and led to cell cycle arrest in the S phase. ERCC6L may regulate the EMT process through the Wnt/β-catenin and Wnt/Notch 3 signaling pathways, thus regulating the tumorigenesis and progression of LUAD. The overexpression of ERCC6L may be a biological indicator for the diagnosis and prognosis of LUAD. ERCC6L may be a novel molecular target for the treatment of lung cancer.

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Prognostic Value of Excision Repair Cross-Complementing mRNA Expression in Gastric Cancer

Cited by 7 publications

References 50 publications

Association of ERCC family mutations with prognosis and immune checkpoint inhibitors response in multiple cancers

Association of ERCC family mutations with prognosis and immune checkpoint inhibitors response in multiple cancers

DNA Damage Response Gene-Based Subtypes Associated With Clinical Outcomes in Early-Stage Lung Adenocarcinoma

Overexpression of ERCC6L correlates with poor prognosis and confers malignant phenotypes of lung adenocarcinoma

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