TY - JOUR
T1 - Prognostic immune markers for recurrence and survival in locally advanced esophageal adenocarcinoma
AU - Babar, Laila
AU - Kosovec, Juliann E.
AU - Jahangiri, Vida
AU - Chowdhury, Nobel
AU - Zheng, Ping
AU - Omstead, Ashten N.
AU - Salvitti, Madison S.
AU - Smith, Matthew A.
AU - Goel, Ajay
AU - Kelly, Ronan J.
AU - Jobe, Blair A.
AU - Zaidi, Ali H.
N1 - Publisher Copyright:
Copyright: Babar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Treatment options and risk stratification for esophageal adenocarcinomas (EAC) currently rely on pathological criteria such as tumor staging. However, with advancement in immune modulated treatments, there is a need for accurate predictive biomarkers that will help identify high-risk patients and provide novel therapeutic targets. Hence, we analyzed as prognostic classifiers a host of histopathological parameters in conjunction with novel immune biomarkers. Specifically, gene expression levels for CXCL9, IDO1, LAG3, and TIM3 were established in treatment naïve samples. Additionally, PD-L1 and CD8 positivity was determined by immunohistochemical staining. Based on our finding, a Cox model consisting of pathological complete response (CR), LAG3, and CXCL9 provided improved predictability for disease-free survival (DFS) compared to CR alone, and it demonstrated statistical significance for predictability of recurrence (p=0.0001). Likewise, for overall survival (OS), a Cox model constituted of TIM3, CR, and IDO1 performed better than CR alone, and it demonstrated statistical significance for predictability of survival (p = 0.0004). TIM3 was identified as the best predictor for OS (HR=4.43, p=0.0023). In conclusion, given the paucity of treatment options for EAC, evaluation of these biomarkers early in the disease course will lead to better risk stratification of patients and much needed alternatives for improved therapy.
AB - Treatment options and risk stratification for esophageal adenocarcinomas (EAC) currently rely on pathological criteria such as tumor staging. However, with advancement in immune modulated treatments, there is a need for accurate predictive biomarkers that will help identify high-risk patients and provide novel therapeutic targets. Hence, we analyzed as prognostic classifiers a host of histopathological parameters in conjunction with novel immune biomarkers. Specifically, gene expression levels for CXCL9, IDO1, LAG3, and TIM3 were established in treatment naïve samples. Additionally, PD-L1 and CD8 positivity was determined by immunohistochemical staining. Based on our finding, a Cox model consisting of pathological complete response (CR), LAG3, and CXCL9 provided improved predictability for disease-free survival (DFS) compared to CR alone, and it demonstrated statistical significance for predictability of recurrence (p=0.0001). Likewise, for overall survival (OS), a Cox model constituted of TIM3, CR, and IDO1 performed better than CR alone, and it demonstrated statistical significance for predictability of survival (p = 0.0004). TIM3 was identified as the best predictor for OS (HR=4.43, p=0.0023). In conclusion, given the paucity of treatment options for EAC, evaluation of these biomarkers early in the disease course will lead to better risk stratification of patients and much needed alternatives for improved therapy.
KW - CXCL9
KW - Esophageal adenocarcinoma
KW - IDO1
KW - LAG3
KW - TIM3
UR - https://www.scopus.com/pages/publications/85069441729
M3 - Article
AN - SCOPUS:85069441729
SN - 1949-2553
VL - 10
SP - 4546
EP - 4555
JO - Oncotarget
JF - Oncotarget
IS - 44
ER -