ERCC5 (ERCC Excision Repair 5 Endonuclease 2)

The integrated analysis of longitudinal WES data from primary tumors and matched PDXs enabled the identification of a core set of conserved, potentially deleterious mutations. The four prioritized mutations (PTPRK, PIK3CB, LRP1B, and IGF2R) provide new insights into the genetic landscape of gastric cancer and represent promising candidates for the development of targeted therapeutic strategies.

Although several DNA repair gene polymorphisms have been explored, findings remain inconsistent and limited by populations and SNPs studied. Larger, well-designed studies with standardized methodologies are needed to confirm these associations and identify genetic markers for predicting high-risk patients for CIO.

Furthermore, the expression of both genes remained unaffected by key clinical variables, including smoking, diabetes, hypertension, nodule presence, PSA level, Gleason, and PIRADS scores. The high expression of the ERCC5 gene in prostate cancer suggests that the NER pathway plays a significant role in this disease, and that ERCC5 may be considered a potential biomarker.

Furthermore, the slope of the GPA Mf dose-response curve was significantly higher in the cancer group than in the cancer-free group among Hiroshima survivors whose rs751402 genotype was the major homozygote. These findings suggest that ERCC5 may play a crucial role in the individual differences observed in HSC somatic gene mutability, as well as in cancer susceptibility after radiation exposure.

These findings suggest that SNPs in DNA repair genes, particularly XPC rs2228001, play a crucial role in modulating the prognosis of CCA.

ERCC5 mutation-related diseases were characterized by mild to severe clinical phenotypes. In addition to tumors, liver function should be considered in ERCC5-related diseases, and patients should be cautious with medication to avoid drug-induced liver injury.

Overall survival is lower compared to national and international data. Despite the small number of patients referred to genetic testing, it is important to search for germline mutations to improve patients' diagnosis and treatment.

Additionally, four male-specific hub genes-DAXX, IKBKB, PDGFRA, and PPARG-were immune-related and showed sex-differential correlations with immune cell infiltration, with three of them associated with AR signaling regulation. These findings provide new insights into the molecular basis of sex differences in bladder cancer and could pave the way for more personalized and effective therapeutic strategies tailored to male and female patients.

Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP (p = 0.24 for PFS and p = 0.14 for OS) and of the rs13181 and rs1799793 ERCC2 SNPs (p = 0.43 and p = 0.26 for PFS and p = 0.21 and p = 0.16 for OS, respectively) compared to patients with homozygous mutant genotypes. The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.

This study of multiple cohorts identifies CHEK2 as a candidate susceptibility gene for DFSP. Additional epidemiologic and functional studies are needed to further characterize this potential gene-tumor relationship.

Especially, SNPs in ATP7B, ERCC-1, ERCC-2, MATE-1, OCT-2, ABCB-1, ABCC-1, ABCG-2, ABCC-2, SLC22A, ERCC-5, BRCA-1, GSTM-3, GSTM-4 and GSTM-5 genes appear to be associated with the therapeutic response and/or adverse effects of cisplatin. We recommend utilizing this information to minimize the risk of treatment failure due to chemoresistance and adverse effects on other organs.

Overall, among the eight compounds identified as the most promising, three of them revealed to significantly increase the impact of cisplatin. The inherent cytotoxicity of these compounds was further investigated in a non-tumoral lung cell line (BEAS-2B cells), which resulted in the identification of two non-cytotoxic candidates to be used in combination with cisplatin in order to improve its efficacy in NSCLC therapy.