Validation of microRNA pathway polymorphisms in esophageal adenocarcinoma survival

Olusola O. Faluyi; Lawson Eng; Xin Qiu; Jiahua Che; Qihuang Zhang; Dangxiao Cheng; Nanjiao Ying; Alvina Tse; Qin Kuang; Lorin Dodbiba; Daniel J. Renouf; Sharon Marsh; Sevtap Savas; Helen J. Mackay; Jennifer J. Knox; Gail E. Darling; Rebecca K.S. Wong; Wei Xu; Abul Kalam Azad; Geoffrey Liu

doi:10.1002/cam4.989

Validation of microRNA pathway polymorphisms in esophageal adenocarcinoma survival

Olusola O. Faluyi, Lawson Eng, Xin Qiu, Jiahua Che, Qihuang Zhang, Dangxiao Cheng, Nanjiao Ying, Alvina Tse, Qin Kuang, Lorin Dodbiba, Daniel J. Renouf, Sharon Marsh, Sevtap Savas, Helen J. Mackay, Jennifer J. Knox, Gail E. Darling, Rebecca K.S. Wong, Wei Xu, Abul Kalam Azad, Geoffrey Liu

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Polymorphisms in miRNA and miRNA pathway genes have been previously associated with cancer risk and outcome, but have not been studied in esophageal adenocarcinoma outcomes. Here, we evaluate candidate miRNA pathway polymorphisms in esophageal adenocarcinoma prognosis and attempt to validate them in an independent cohort of esophageal adenocarcinoma patients. Among 231 esophageal adenocarcinoma patients of all stages/treatment plans, 38 candidate genetic polymorphisms (17 biogenesis, 9 miRNA targets, 5 pri-miRNA, 7 pre-miRNA) were genotyped and analyzed. Cox proportional hazard models adjusted for sociodemographic and clinicopathological covariates helped assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then evaluated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis, and median OS and PFS were 20 and 12 months, respectively. GEMIN3 rs197412 (aHR = 1.37, 95%CI: [1.04–1.80]; P = 0.02), hsa-mir-124-1 rs531564 (aHR = 0.60, 95% CI: [0.53–0.90]; P = 0.05), and KIAA0423 rs1053667 (aHR = 0.51, 95% CI: [0.28–0.96]; P = 0.04) were found associated with OS. Furthermore, GEMIN3 rs197412 (aHR = 1.33, 95% CI: [1.03–1.74]; P = 0.03) and KRT81 rs3660 (aHR = 1.29, 95% CI: [1.01–1.64]; P = 0.04) were found associated with PFS. Although none of these polymorphisms were significant in the second cohort, hsa-mir-124-1 rs531564 and KIAA0423 rs1053667 had trends in the same direction; when both cohorts were combined together, GEMIN3 rs197412, hsa-mir-124-1 rs531564, and KIAA0423 rs1053667 remained significantly associated with OS. We demonstrate the association of multiple miRNA pathway polymorphisms with esophageal adenocarcinoma prognosis in a discovery cohort of patients, which did not validate in a separate cohort but had consistent associations in the pooled cohort. Larger studies are required to confirm/validate the prognostic value of these polymorphisms in esophageal adenocarcinoma.

Original language	English (US)
Pages (from-to)	361-373
Number of pages	13
Journal	Cancer Medicine
Volume	6
Issue number	2
DOIs	https://doi.org/10.1002/cam4.989
State	Published - Feb 1 2017
Externally published	Yes

Keywords

Esophageal adenocarcinoma
miRNA pathways
polymorphisms
prognosis

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/cam4.989

Cite this

Faluyi, O. O., Eng, L., Qiu, X., Che, J., Zhang, Q., Cheng, D., Ying, N., Tse, A., Kuang, Q., Dodbiba, L., Renouf, D. J., Marsh, S., Savas, S., Mackay, H. J., Knox, J. J., Darling, G. E., Wong, R. K. S., Xu, W., Azad, A. K., & Liu, G. (2017). Validation of microRNA pathway polymorphisms in esophageal adenocarcinoma survival. Cancer Medicine, 6(2), 361-373. https://doi.org/10.1002/cam4.989

@article{029d321ff016497ea7d6a7bd3c3f6288,

title = "Validation of microRNA pathway polymorphisms in esophageal adenocarcinoma survival",

abstract = "Polymorphisms in miRNA and miRNA pathway genes have been previously associated with cancer risk and outcome, but have not been studied in esophageal adenocarcinoma outcomes. Here, we evaluate candidate miRNA pathway polymorphisms in esophageal adenocarcinoma prognosis and attempt to validate them in an independent cohort of esophageal adenocarcinoma patients. Among 231 esophageal adenocarcinoma patients of all stages/treatment plans, 38 candidate genetic polymorphisms (17 biogenesis, 9 miRNA targets, 5 pri-miRNA, 7 pre-miRNA) were genotyped and analyzed. Cox proportional hazard models adjusted for sociodemographic and clinicopathological covariates helped assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then evaluated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis, and median OS and PFS were 20 and 12 months, respectively. GEMIN3 rs197412 (aHR = 1.37, 95%CI: [1.04–1.80]; P = 0.02), hsa-mir-124-1 rs531564 (aHR = 0.60, 95% CI: [0.53–0.90]; P = 0.05), and KIAA0423 rs1053667 (aHR = 0.51, 95% CI: [0.28–0.96]; P = 0.04) were found associated with OS. Furthermore, GEMIN3 rs197412 (aHR = 1.33, 95% CI: [1.03–1.74]; P = 0.03) and KRT81 rs3660 (aHR = 1.29, 95% CI: [1.01–1.64]; P = 0.04) were found associated with PFS. Although none of these polymorphisms were significant in the second cohort, hsa-mir-124-1 rs531564 and KIAA0423 rs1053667 had trends in the same direction; when both cohorts were combined together, GEMIN3 rs197412, hsa-mir-124-1 rs531564, and KIAA0423 rs1053667 remained significantly associated with OS. We demonstrate the association of multiple miRNA pathway polymorphisms with esophageal adenocarcinoma prognosis in a discovery cohort of patients, which did not validate in a separate cohort but had consistent associations in the pooled cohort. Larger studies are required to confirm/validate the prognostic value of these polymorphisms in esophageal adenocarcinoma.",

keywords = "Esophageal adenocarcinoma, miRNA pathways, polymorphisms, prognosis",

author = "Faluyi, {Olusola O.} and Lawson Eng and Xin Qiu and Jiahua Che and Qihuang Zhang and Dangxiao Cheng and Nanjiao Ying and Alvina Tse and Qin Kuang and Lorin Dodbiba and Renouf, {Daniel J.} and Sharon Marsh and Sevtap Savas and Mackay, {Helen J.} and Knox, {Jennifer J.} and Darling, {Gail E.} and Wong, {Rebecca K.S.} and Wei Xu and Azad, {Abul Kalam} and Geoffrey Liu",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",

year = "2017",

month = feb,

day = "1",

doi = "10.1002/cam4.989",

language = "English (US)",

volume = "6",

pages = "361--373",

journal = "Cancer Medicine",

issn = "2045-7634",

publisher = "John Wiley and Sons Ltd",

number = "2",

}

TY - JOUR

T1 - Validation of microRNA pathway polymorphisms in esophageal adenocarcinoma survival

AU - Faluyi, Olusola O.

AU - Eng, Lawson

AU - Qiu, Xin

AU - Che, Jiahua

AU - Zhang, Qihuang

AU - Cheng, Dangxiao

AU - Ying, Nanjiao

AU - Tse, Alvina

AU - Kuang, Qin

AU - Dodbiba, Lorin

AU - Renouf, Daniel J.

AU - Marsh, Sharon

AU - Savas, Sevtap

AU - Mackay, Helen J.

AU - Knox, Jennifer J.

AU - Darling, Gail E.

AU - Wong, Rebecca K.S.

AU - Xu, Wei

AU - Azad, Abul Kalam

AU - Liu, Geoffrey

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Polymorphisms in miRNA and miRNA pathway genes have been previously associated with cancer risk and outcome, but have not been studied in esophageal adenocarcinoma outcomes. Here, we evaluate candidate miRNA pathway polymorphisms in esophageal adenocarcinoma prognosis and attempt to validate them in an independent cohort of esophageal adenocarcinoma patients. Among 231 esophageal adenocarcinoma patients of all stages/treatment plans, 38 candidate genetic polymorphisms (17 biogenesis, 9 miRNA targets, 5 pri-miRNA, 7 pre-miRNA) were genotyped and analyzed. Cox proportional hazard models adjusted for sociodemographic and clinicopathological covariates helped assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then evaluated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis, and median OS and PFS were 20 and 12 months, respectively. GEMIN3 rs197412 (aHR = 1.37, 95%CI: [1.04–1.80]; P = 0.02), hsa-mir-124-1 rs531564 (aHR = 0.60, 95% CI: [0.53–0.90]; P = 0.05), and KIAA0423 rs1053667 (aHR = 0.51, 95% CI: [0.28–0.96]; P = 0.04) were found associated with OS. Furthermore, GEMIN3 rs197412 (aHR = 1.33, 95% CI: [1.03–1.74]; P = 0.03) and KRT81 rs3660 (aHR = 1.29, 95% CI: [1.01–1.64]; P = 0.04) were found associated with PFS. Although none of these polymorphisms were significant in the second cohort, hsa-mir-124-1 rs531564 and KIAA0423 rs1053667 had trends in the same direction; when both cohorts were combined together, GEMIN3 rs197412, hsa-mir-124-1 rs531564, and KIAA0423 rs1053667 remained significantly associated with OS. We demonstrate the association of multiple miRNA pathway polymorphisms with esophageal adenocarcinoma prognosis in a discovery cohort of patients, which did not validate in a separate cohort but had consistent associations in the pooled cohort. Larger studies are required to confirm/validate the prognostic value of these polymorphisms in esophageal adenocarcinoma.

AB - Polymorphisms in miRNA and miRNA pathway genes have been previously associated with cancer risk and outcome, but have not been studied in esophageal adenocarcinoma outcomes. Here, we evaluate candidate miRNA pathway polymorphisms in esophageal adenocarcinoma prognosis and attempt to validate them in an independent cohort of esophageal adenocarcinoma patients. Among 231 esophageal adenocarcinoma patients of all stages/treatment plans, 38 candidate genetic polymorphisms (17 biogenesis, 9 miRNA targets, 5 pri-miRNA, 7 pre-miRNA) were genotyped and analyzed. Cox proportional hazard models adjusted for sociodemographic and clinicopathological covariates helped assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then evaluated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis, and median OS and PFS were 20 and 12 months, respectively. GEMIN3 rs197412 (aHR = 1.37, 95%CI: [1.04–1.80]; P = 0.02), hsa-mir-124-1 rs531564 (aHR = 0.60, 95% CI: [0.53–0.90]; P = 0.05), and KIAA0423 rs1053667 (aHR = 0.51, 95% CI: [0.28–0.96]; P = 0.04) were found associated with OS. Furthermore, GEMIN3 rs197412 (aHR = 1.33, 95% CI: [1.03–1.74]; P = 0.03) and KRT81 rs3660 (aHR = 1.29, 95% CI: [1.01–1.64]; P = 0.04) were found associated with PFS. Although none of these polymorphisms were significant in the second cohort, hsa-mir-124-1 rs531564 and KIAA0423 rs1053667 had trends in the same direction; when both cohorts were combined together, GEMIN3 rs197412, hsa-mir-124-1 rs531564, and KIAA0423 rs1053667 remained significantly associated with OS. We demonstrate the association of multiple miRNA pathway polymorphisms with esophageal adenocarcinoma prognosis in a discovery cohort of patients, which did not validate in a separate cohort but had consistent associations in the pooled cohort. Larger studies are required to confirm/validate the prognostic value of these polymorphisms in esophageal adenocarcinoma.

KW - Esophageal adenocarcinoma

KW - miRNA pathways

KW - polymorphisms

KW - prognosis

UR - http://www.scopus.com/inward/record.url?scp=85009495146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009495146&partnerID=8YFLogxK

U2 - 10.1002/cam4.989

DO - 10.1002/cam4.989

M3 - Article

C2 - 28074552

AN - SCOPUS:85009495146

SN - 2045-7634

VL - 6

SP - 361

EP - 373

JO - Cancer Medicine

JF - Cancer Medicine

IS - 2

ER -

Validation of microRNA pathway polymorphisms in esophageal adenocarcinoma survival

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this