<p>Association between single nucleotide polymorphisms of <em>NOTCH</em> signaling pathway-related genes and the prognosis of NSCLC</p>

Abstract

Objective In this study, we analyzed the association between genetic variants of genes in the NOTCH signaling pathway and the prognosis of non-small-cell lung cancer (NSCLC) in the Chinese population. We also explored the interaction between genetic and epidemiological factors for the test group. Methods We performed genotyping of 987 NSCLC patients. Then, we used Cox proportional hazard models to analyze the associations between single-nucleotide polymorphisms (SNPs) and the prognosis of NSCLC. We employed Stata software to test the heterogeneity of associations between subgroups, and we analyzed the additive and multiplicative interactions between SNPs and epidemiologic factors. Results This work revealed the important prognostic and predictive value of rs915894 in the NOTCH4 gene, which may be regarded as a promising prognosis biomarker of NSCLC. Cox regression analysis indicated that the C allele of rs915894 is associated with longer survival and decreased risk of death in NSCLC (codominant model: adjusted HR =0.83, 95% CI =0.70–0.99; dominant model: adjusted HR =0.83, 95% CI =0.71–0.98). Additional stepwise regression analysis suggested that this SNP is an independently favorable factor for the prognosis of NSCLC (dominant model: adjusted HR =0.85, 95% CI =0.72–0.99). This protective effect is more pronounced for patients who are not smokers, have a history of other lung diseases, or have a family history of cancer. We also detected statistically significant additive and multiplicative interactions between rs915894 and smoking, rs915894 and history of lung diseases, and rs915894 and family history of cancer, which all affect NSCLC survival. Conclusion This study demonstrated that rs915894 in NOTCH 4 may be a genetic marker for NSCLC prognosis in the Chinese population and that rs915894 may have an interactive relationship with epidemiologic factors.

Comprehensive genomic profile of Chinese lung cancer patients and mutation characteristics of individuals resistant to icotinib/gefitinib

“…The Notch signaling pathway has an important regulatory role in a variety of tumor stem cells. Mutations in DNMT3a and NOTCH4 have been reported to be associated with better prognosis in patients with LUAD and NSCLC, respectively 73 , 74 . Similarly, the EGFR-TKI sensitivity of patients with these indicates a good prognosis.…”

The Association Between Heat-Shock Protein Polymorphisms and Prognosis in Lung Cancer Patients Treated With Platinum-Based Chemotherapy

“…Genotype mutations in some key genes, including single nucleotide polymorphisms (SNPs), may cause disorder or over-activation of some specific signaling pathway, leading to tumor development and affect patients' prognosis (Xu et al, 2019). We have found that RAC1 polymorphisms are associated with platinum-based chemotherapy toxicity in lung cancer patients in our previous study (Zou et al, 2016).…”

Genetic Variants in DNA Mismatch Repair Pathway predict prognosis of Lung Cancer patients with receiving Platinum-Based Chemotherapy

“…International Publisher [14][15][16][17][18][19][20]. It is important to discern some new biomarkers that can be used to predict the prognosis of platinum-based chemotherapy.…”