Research Paper|Volume 13, Issue 7|pp 10369—10386

Tumor infiltrating lymphocyte signature is associated with single nucleotide polymorphisms and predicts survival in esophageal squamous cell carcinoma patients

Chen Suo^1,², Huiyao Chen^1,³, Franciszek Binczyk⁴, Renjia Zhao¹, Jiahui Fan⁵, Xiaorong Yang⁶, Ziyu Yuan², David Kreil⁷, Paweł Łabaj⁸, Tiejun Zhang^1,², Ming Lu⁶, Li Jin^2,⁹, Joanna Polańska⁴, Xingdong Chen^2,⁹, Weimin Ye¹⁰

¹Department of Epidemiology and Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, China
²Fudan University Taizhou Institute of Health Sciences, Taizhou, China
³Center for Molecular Medicine of Children's Hospital of Fudan University, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
⁴Silesian University of Technology, Data Mining Division, Gliwice, Poland
⁵State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
⁶Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China
⁷IMBT Bioinformatics Research, Boku University Vienn, Vienna, Austria
⁸Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland
⁹Human Phenome Institute, Fudan University, Shanghai, China
¹⁰Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden

* Equal contribution

# Co-first authors

Received: October 7, 2020Accepted: February 8, 2021Published: April 4, 2021

https://doi.org/10.18632/aging.202798

Copyright: © 2021 Suo 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.

Abstract

Purpose: Esophageal cancer is the sixth leading cause of cancer-related death worldwide, and is associated with a poor prognosis. Stromal tumor infiltrating lymphocytes (sTIL) and certain single nucleotide polymorphisms (SNPs) have been found to be predictive of patient survival. In this study, we explored the association between SNPs and sTIL regarding the predictability of disease-free survival in patients with esophageal squamous cell carcinoma (ESCC).

Materials and methods: We collected 969 pathologically confirmed ESCC patients from 2010 to 2013 and genotyped 101 SNPs from 59 genes. The number of sTIL for each patient was determined using an automatic algorithm. A Kruskal-Wallis test was used to determine the association between genotype and sTIL. The genotypes and clinical factors related to survival were analyzed using a Kaplan-Meier curve, Cox proportional hazards model, and log-rank test.

Results: The median age of the patients was 67 (42-85 years), there was a median follow-up of 851.5 days and 586 patients died. The univariable analysis showed that 10 of the 101 SNPs were associated with sTIL. Six SNPs were also associated with disease-free survival. A multivariable analysis revealed that sTIL, rs1801131, rs25487, and rs8030672 were independent prognostic markers for ESCC patients. The model combining SNPs, clinical characteristics and sTIL outperformed the model with clinical characteristics alone for predicting outcomes in ESCC patients.

Conclusion: We discovered 10 SNPs associated with sTIL in ESCC and we built a model of sTIL, SNPs and clinical characteristics with improved prediction of survival in ESCC patients.