Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small‐cell lung cancer patients
Abstract Background Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small‐cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. Methods In this study, we evaluated the association between putative functional polymorphisms...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Language: | English |
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Wiley
2023-05-01
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| Series: | Thoracic Cancer |
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| Online Access: | https://doi.org/10.1111/1759-7714.14839 |
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| author | Sunwoong Lee Seung Soo Yoo Jin Eun Choi Mi Jeong Hong Sook Kyung Do Jang Hyuck Lee Won Ki Lee Ji Eun Park Sun Ha Choi Hyewon Seo Jaehee Lee Shin Yup Lee Seung Ick Cha Chang Ho Kim Hyo‐Gyoung Kang Jae Yong Park |
| author_facet | Sunwoong Lee Seung Soo Yoo Jin Eun Choi Mi Jeong Hong Sook Kyung Do Jang Hyuck Lee Won Ki Lee Ji Eun Park Sun Ha Choi Hyewon Seo Jaehee Lee Shin Yup Lee Seung Ick Cha Chang Ho Kim Hyo‐Gyoung Kang Jae Yong Park |
| author_sort | Sunwoong Lee |
| collection | DOAJ |
| description | Abstract Background Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small‐cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. Methods In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. Results The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (p = 0.04 and p = 0.04, respectively). The SNP rs11265375C>T in nescient helix–loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (p = 0.04 and p = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (p = 4 × 10−6). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (p = 0.001). Conclusion These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC. |
| first_indexed | 2024-04-09T14:58:12Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-04-09T14:58:12Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-0ffd19c0dffd4e939929578dfbeb601b2023-05-01T23:44:43ZengWileyThoracic Cancer1759-77061759-77142023-05-0114131145115210.1111/1759-7714.14839Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small‐cell lung cancer patientsSunwoong Lee0Seung Soo Yoo1Jin Eun Choi2Mi Jeong Hong3Sook Kyung Do4Jang Hyuck Lee5Won Ki Lee6Ji Eun Park7Sun Ha Choi8Hyewon Seo9Jaehee Lee10Shin Yup Lee11Seung Ick Cha12Chang Ho Kim13Hyo‐Gyoung Kang14Jae Yong Park15Department of Biochemistry and Cell Biology, School of Medicine Kyungpook National University Daegu Republic of KoreaDepartment of Internal Medicine, School of Medicine Kyungpook National University, Kyungpook National University Hospital Daegu Republic of KoreaDepartment of Biochemistry and Cell Biology, School of Medicine Kyungpook National University Daegu Republic of KoreaDepartment of Biochemistry and Cell Biology, School of Medicine Kyungpook National University Daegu Republic of KoreaDepartment of Biochemistry and Cell Biology, School of Medicine Kyungpook National University Daegu Republic of KoreaDepartment of Biochemistry and Cell Biology, School of Medicine Kyungpook National University Daegu Republic of KoreaMedical Research Collaboration Center in Kyungpook National University Hospital and School of Medicine Kyungpook National University Daegu Republic of KoreaDepartment of Internal Medicine, School of Medicine Kyungpook National University, Kyungpook National University Hospital Daegu Republic of KoreaDepartment of Internal Medicine, School of Medicine Kyungpook National University, Kyungpook National University Hospital Daegu Republic of KoreaDepartment of Internal Medicine, School of Medicine Kyungpook National University, Kyungpook National University Hospital Daegu Republic of KoreaDepartment of Internal Medicine, School of Medicine Kyungpook National University, Kyungpook National University Hospital Daegu Republic of KoreaDepartment of Internal Medicine, School of Medicine Kyungpook National University, Kyungpook National University Hospital Daegu Republic of KoreaDepartment of Internal Medicine, School of Medicine Kyungpook National University, Kyungpook National University Hospital Daegu Republic of KoreaDepartment of Internal Medicine, School of Medicine Kyungpook National University, Kyungpook National University Hospital Daegu Republic of KoreaDepartment of Biochemistry and Cell Biology, School of Medicine Kyungpook National University Daegu Republic of KoreaDepartment of Biochemistry and Cell Biology, School of Medicine Kyungpook National University Daegu Republic of KoreaAbstract Background Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small‐cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. Methods In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. Results The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (p = 0.04 and p = 0.04, respectively). The SNP rs11265375C>T in nescient helix–loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (p = 0.04 and p = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (p = 4 × 10−6). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (p = 0.001). Conclusion These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC.https://doi.org/10.1111/1759-7714.14839NEUROD1NHLH1SCLCSEMA6ASNPSurvival |
| spellingShingle | Sunwoong Lee Seung Soo Yoo Jin Eun Choi Mi Jeong Hong Sook Kyung Do Jang Hyuck Lee Won Ki Lee Ji Eun Park Sun Ha Choi Hyewon Seo Jaehee Lee Shin Yup Lee Seung Ick Cha Chang Ho Kim Hyo‐Gyoung Kang Jae Yong Park Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small‐cell lung cancer patients Thoracic Cancer NEUROD1 NHLH1 SCLC SEMA6A SNP Survival |
| title | Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small‐cell lung cancer patients |
| title_full | Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small‐cell lung cancer patients |
| title_fullStr | Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small‐cell lung cancer patients |
| title_full_unstemmed | Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small‐cell lung cancer patients |
| title_short | Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small‐cell lung cancer patients |
| title_sort | genetic variants of neurod1 target genes are associated with clinical outcomes of small cell lung cancer patients |
| topic | NEUROD1 NHLH1 SCLC SEMA6A SNP Survival |
| url | https://doi.org/10.1111/1759-7714.14839 |
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