Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome

Abstract This study was conducted to investigate the impact of genetic variants of immune checkpoint genes on the treatment outcome in small cell lung cancer (SCLC). In the present study, 261 platinum doublet-treated SCLC patients were enrolled. A total of 96 polymorphisms in 33 immune checkpoint-re...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jang Hyuck Lee, Seung Soo Yoo, Mi Jeong Hong, Jin Eun Choi, Soyoun Kim, Hyo-Gyoung Kang, Sook Kyung Do, Ji Hyun Kim, Sun Ah Baek, Won Kee Lee, Jae Do Yoo, Sun Ha Choi, Yong Hoon Lee, Hyewon Seo, Jaehee Lee, Shin Yup Lee, Seung Ick Cha, Chang Ho Kim, Jae Yong Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/87ca5758799b4b35a34b7677f223a6ae
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:87ca5758799b4b35a34b7677f223a6ae
record_format	dspace
spelling	oai:doaj.org-article:87ca5758799b4b35a34b7677f223a6ae2021-12-02T13:51:16ZImpact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome10.1038/s41598-021-81260-12045-2322https://doaj.org/article/87ca5758799b4b35a34b7677f223a6ae2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81260-1https://doaj.org/toc/2045-2322Abstract This study was conducted to investigate the impact of genetic variants of immune checkpoint genes on the treatment outcome in small cell lung cancer (SCLC). In the present study, 261 platinum doublet-treated SCLC patients were enrolled. A total of 96 polymorphisms in 33 immune checkpoint-related genes were selected, and their association with chemotherapy response and survival outcomes were analyzed. Among the polymorphisms studied, CD155 rs1058402G > A (Ala67Thr, A67T) and CD226 rs763361C > T (Gly307Ser, G307S) were significantly associated with SCLC treatment outcome. The rs1058402G > A had a worse chemotherapy response and overall survival (under a dominant model, adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.27–0.99, P = 0.05; adjusted hazard ratio [aHR] = 1.55, 95% CI = 1.12–2.14, P = 0.01, respectively). The rs763361C > T had better chemotherapy response and overall survival (under a dominant model, aOR = 2.03, 95% CI = 1.10–3.75, P = 0.02; aHR = 0.69, 95% CI = 0.51–0.94, P = 0.02, respectively). When the rs1058402GA/AA and rs763361CC genotypes were combined, the chemotherapy response and overall survival were significantly decreased as the number of bad genotypes increased (aOR = 0.52, 95% CI = 0.33–0.81, Ptrend = 0.004; aHR = 1.48, 95% CI = 1.19–1.84, Ptrend = 4 × 10−4, respectively). The 3-D structural model showed that CD155 A67T created a new hydrogen bond and structural change on CD155. These changes resulted in extending the distance and losing the hydrogen bonds between CD155 and CD226, thus weakening CD155/CD226 binding activity. In conclusion, CD155 rs1058402G > A and CD226 rs763361C > T may be useful for predicting the clinical outcomes of SCLC patients after chemotherapy.Jang Hyuck LeeSeung Soo YooMi Jeong HongJin Eun ChoiSoyoun KimHyo-Gyoung KangSook Kyung DoJi Hyun KimSun Ah BaekWon Kee LeeJae Do YooSun Ha ChoiYong Hoon LeeHyewon SeoJaehee LeeShin Yup LeeSeung Ick ChaChang Ho KimJae Yong ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jang Hyuck Lee Seung Soo Yoo Mi Jeong Hong Jin Eun Choi Soyoun Kim Hyo-Gyoung Kang Sook Kyung Do Ji Hyun Kim Sun Ah Baek Won Kee Lee Jae Do Yoo Sun Ha Choi Yong Hoon Lee Hyewon Seo Jaehee Lee Shin Yup Lee Seung Ick Cha Chang Ho Kim Jae Yong Park Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome
description	Abstract This study was conducted to investigate the impact of genetic variants of immune checkpoint genes on the treatment outcome in small cell lung cancer (SCLC). In the present study, 261 platinum doublet-treated SCLC patients were enrolled. A total of 96 polymorphisms in 33 immune checkpoint-related genes were selected, and their association with chemotherapy response and survival outcomes were analyzed. Among the polymorphisms studied, CD155 rs1058402G > A (Ala67Thr, A67T) and CD226 rs763361C > T (Gly307Ser, G307S) were significantly associated with SCLC treatment outcome. The rs1058402G > A had a worse chemotherapy response and overall survival (under a dominant model, adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.27–0.99, P = 0.05; adjusted hazard ratio [aHR] = 1.55, 95% CI = 1.12–2.14, P = 0.01, respectively). The rs763361C > T had better chemotherapy response and overall survival (under a dominant model, aOR = 2.03, 95% CI = 1.10–3.75, P = 0.02; aHR = 0.69, 95% CI = 0.51–0.94, P = 0.02, respectively). When the rs1058402GA/AA and rs763361CC genotypes were combined, the chemotherapy response and overall survival were significantly decreased as the number of bad genotypes increased (aOR = 0.52, 95% CI = 0.33–0.81, Ptrend = 0.004; aHR = 1.48, 95% CI = 1.19–1.84, Ptrend = 4 × 10−4, respectively). The 3-D structural model showed that CD155 A67T created a new hydrogen bond and structural change on CD155. These changes resulted in extending the distance and losing the hydrogen bonds between CD155 and CD226, thus weakening CD155/CD226 binding activity. In conclusion, CD155 rs1058402G > A and CD226 rs763361C > T may be useful for predicting the clinical outcomes of SCLC patients after chemotherapy.
format	article
author	Jang Hyuck Lee Seung Soo Yoo Mi Jeong Hong Jin Eun Choi Soyoun Kim Hyo-Gyoung Kang Sook Kyung Do Ji Hyun Kim Sun Ah Baek Won Kee Lee Jae Do Yoo Sun Ha Choi Yong Hoon Lee Hyewon Seo Jaehee Lee Shin Yup Lee Seung Ick Cha Chang Ho Kim Jae Yong Park
author_facet	Jang Hyuck Lee Seung Soo Yoo Mi Jeong Hong Jin Eun Choi Soyoun Kim Hyo-Gyoung Kang Sook Kyung Do Ji Hyun Kim Sun Ah Baek Won Kee Lee Jae Do Yoo Sun Ha Choi Yong Hoon Lee Hyewon Seo Jaehee Lee Shin Yup Lee Seung Ick Cha Chang Ho Kim Jae Yong Park
author_sort	Jang Hyuck Lee
title	Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome
title_short	Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome
title_full	Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome
title_fullStr	Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome
title_full_unstemmed	Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome
title_sort	impact of immune checkpoint gene cd155 ala67thr and cd226 gly307ser polymorphisms on small cell lung cancer clinical outcome
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/87ca5758799b4b35a34b7677f223a6ae
work_keys_str_mv	AT janghyucklee impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT seungsooyoo impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT mijeonghong impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT jineunchoi impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT soyounkim impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT hyogyoungkang impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT sookkyungdo impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT jihyunkim impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT sunahbaek impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT wonkeelee impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT jaedoyoo impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT sunhachoi impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT yonghoonlee impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT hyewonseo impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT jaeheelee impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT shinyuplee impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT seungickcha impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT changhokim impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome AT jaeyongpark impactofimmunecheckpointgenecd155ala67thrandcd226gly307serpolymorphismsonsmallcelllungcancerclinicaloutcome
_version_	1718392390628147200

Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome

Ejemplares similares