Genetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma
Abstract We investigated the association between genetic variants in the histone modification regions and the prognosis of lung adenocarcinoma after curative surgery. Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The SNPs were analyzed in a discovery se...
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2021
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oai:doaj.org-article:ab77e259b9c54b8aab65c9c23d314e942021-11-08T10:47:54ZGenetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma10.1038/s41598-021-00909-z2045-2322https://doaj.org/article/ab77e259b9c54b8aab65c9c23d314e942021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00909-zhttps://doaj.org/toc/2045-2322Abstract We investigated the association between genetic variants in the histone modification regions and the prognosis of lung adenocarcinoma after curative surgery. Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The SNPs were analyzed in a discovery set (n = 166) and a validation set (n = 238). The associations of the SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed. A total of 279 SNPs were selected for genotyping. Among these, CAPN1 rs17583C>T was significantly associated with better OS and DFS (P = 0.001 and P = 0.007, respectively), and LINC00959 rs4751162A>G was significantly associated with worse DFS (P = 0.008). Luciferase assays showed a significantly lower promoter activity of CAPN1 in the rs17583 T allele than C allele (P = 0.008), and consistently the CT + TT genotypes had significantly lower CAPN1 expression than CC genotype (P = 0.01) in clinical samples. The rs4751162 G allele had higher promoter activity of GLRX3 than A allele (P = 0.05). The motif analyses and ChIP-qPCR confirmed that the variants are located in the active promoter/enhancer regions where transcription factor binding occurs. This study showed that genetic variants in the histone modification regions could predict the prognosis of lung adenocarcinoma after surgery.Hyo-Gyoung KangYong Hoon LeeShin Yup LeeJin Eun ChoiSook Kyung DoMi Jeong HongJang Hyuck LeeJi Yun JeongYoung Woo DoEung Bae LeeKyung Min ShinWon Kee LeeSun Ha ChoiHye won SeoSeung Soo YooJaehee LeeSeung Ick ChaChang Ho KimSukki ChoSanghoon JheonJae Yong ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q Hyo-Gyoung Kang Yong Hoon Lee Shin Yup Lee Jin Eun Choi Sook Kyung Do Mi Jeong Hong Jang Hyuck Lee Ji Yun Jeong Young Woo Do Eung Bae Lee Kyung Min Shin Won Kee Lee Sun Ha Choi Hye won Seo Seung Soo Yoo Jaehee Lee Seung Ick Cha Chang Ho Kim Sukki Cho Sanghoon Jheon Jae Yong Park Genetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma |
| description |
Abstract We investigated the association between genetic variants in the histone modification regions and the prognosis of lung adenocarcinoma after curative surgery. Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The SNPs were analyzed in a discovery set (n = 166) and a validation set (n = 238). The associations of the SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed. A total of 279 SNPs were selected for genotyping. Among these, CAPN1 rs17583C>T was significantly associated with better OS and DFS (P = 0.001 and P = 0.007, respectively), and LINC00959 rs4751162A>G was significantly associated with worse DFS (P = 0.008). Luciferase assays showed a significantly lower promoter activity of CAPN1 in the rs17583 T allele than C allele (P = 0.008), and consistently the CT + TT genotypes had significantly lower CAPN1 expression than CC genotype (P = 0.01) in clinical samples. The rs4751162 G allele had higher promoter activity of GLRX3 than A allele (P = 0.05). The motif analyses and ChIP-qPCR confirmed that the variants are located in the active promoter/enhancer regions where transcription factor binding occurs. This study showed that genetic variants in the histone modification regions could predict the prognosis of lung adenocarcinoma after surgery. |
| format |
article |
| author |
Hyo-Gyoung Kang Yong Hoon Lee Shin Yup Lee Jin Eun Choi Sook Kyung Do Mi Jeong Hong Jang Hyuck Lee Ji Yun Jeong Young Woo Do Eung Bae Lee Kyung Min Shin Won Kee Lee Sun Ha Choi Hye won Seo Seung Soo Yoo Jaehee Lee Seung Ick Cha Chang Ho Kim Sukki Cho Sanghoon Jheon Jae Yong Park |
| author_facet |
Hyo-Gyoung Kang Yong Hoon Lee Shin Yup Lee Jin Eun Choi Sook Kyung Do Mi Jeong Hong Jang Hyuck Lee Ji Yun Jeong Young Woo Do Eung Bae Lee Kyung Min Shin Won Kee Lee Sun Ha Choi Hye won Seo Seung Soo Yoo Jaehee Lee Seung Ick Cha Chang Ho Kim Sukki Cho Sanghoon Jheon Jae Yong Park |
| author_sort |
Hyo-Gyoung Kang |
| title |
Genetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma |
| title_short |
Genetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma |
| title_full |
Genetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma |
| title_fullStr |
Genetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma |
| title_full_unstemmed |
Genetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma |
| title_sort |
genetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/ab77e259b9c54b8aab65c9c23d314e94 |
| work_keys_str_mv |
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| _version_ |
1718442651336835072 |