Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery
| Autor: | Dong Kwan Kim, Chang Ho Kim, Eung Bae Lee, Jang Hyuck Lee, Sanghoon Jheon, Won Kee Lee, Yangki Seok, Kyung Min Shin, Young-Chul Kim, Moon Soo Kim, Chi Young Jung, Seung Ick Cha, Seung Soo Yoo, Shin Yup Lee, Ji Yun Jeong, Kook Joo Na, Jae Yong Park, Hyo Gyoung Kang, Chang Kwon Park, Hee Chul Yang, Jin Eun Choi, Mi Jeong Hong, Min Ki Lee, In-Jae Oh, Jong Mog Lee, Jaehee Lee, Sukki Cho, Sook Kyung Do |
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| Rok vydání: | 2018 |
| Předmět: |
Oncology
Male medicine.medical_specialty Lung Neoplasms Genotype Ubiquitin-Protein Ligases Notch signaling pathway Single-nucleotide polymorphism Adenocarcinoma Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Surgical oncology Internal medicine Carcinoma Non-Small-Cell Lung medicine Biomarkers Tumor Humans Stage (cooking) Allele Gene Aged Lung cancer surgery business.industry Prognosis Survival Rate 030220 oncology & carcinogenesis Carcinoma Squamous Cell Carcinoma Large Cell 030211 gastroenterology & hepatology Surgery Female business Follow-Up Studies |
| Zdroj: | Annals of surgical oncology. 26(11) |
| ISSN: | 1534-4681 |
| Popis: | We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC. Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated. Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64–0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71–0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (Ptrend = 0.02) in tumor tissues. These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC. |
| Databáze: | OpenAIRE |
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