Explore association of genes in PDL1/PD1 pathway to radiotherapy survival benefit based on interaction model strategy

Radiation Oncology

Junjie Shen¹  Ruirui Geng¹  Zaixiang Tang¹  Huijun Li¹  Lu Bai¹  Zixuan Du¹  Jingfang Liu²  Peng Sun³  Jianping Cao⁴ 

[1] Department of Biostatistics, School of Public Health, Medical College of Soochow University, 215123, Suzhou, China;Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, 215123, Suzhou, China;Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Soochow University, 215123, Suzhou, China;Department of Otolaryngology, The First Affiliated Hospital of Soochow University, 215123, Suzhou, China;School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, 215006, Suzhou, China;

关键词: Cancers;    Radio-sensitivity;    Gene biomarkers;    PD-1 check point pathway;    Interaction model;   

DOI  :  10.1186/s13014-021-01951-x

来源: Springer

【 摘 要 】

PurposeTo explore the association of genes in “PD-L1 expression and PD-1 check point pathway in cancer” to radiotherapy survival benefit.Methods and materialsGene expression data and clinical information of cancers were downloaded from TCGA. Radiotherapy survival benefit was defined based on interaction model. Fast backward multivariate Cox regression was performed using stacking multiple interpolation data to identify radio-sensitive (RS) genes.ResultsAmong the 73 genes in PD-L1/PD-1 pathway, we identified 24 RS genes in BRCA data set, 25 RS genes in STAD data set and 20 RS genes in HNSC data set, with some crossover genes. Theoretically, there are two types of RS genes. The expression level of Type I RS genes did not affect patients' overall survival (OS), but when receiving radiotherapy, patients with different expression level of Type I RS genes had varied survival benefit. Oppositely, Type II RS genes affected patients' OS. And when receiving radiotherapy, those with lower OS could benefit a lot. Type II RS genes in BRCA had strong positive correlation and closely biological interactions. When performing cluster analysis using these related Type II RS genes, patients could be divided into RS group and non-RS group in BRCA and METABRIC data sets.ConclusionsOur study explored potential radio-sensitive biomarkers of several main cancer types in an important tumor immune checkpoint pathway and revealed a strong association between this pathway and radiotherapy survival benefit. New types of RS genes could be identified based on expanded definition to RS genes.

【 授权许可】

CC BY