Immunity-Related Gene Signature Identifies Subtypes Benefitting From Adjuvant Chemotherapy or Potentially Responding to PD1/PD-L1 Blockage in Pancreatic Cancer

Hao Qian; Hongzhe Li; Junjie Xie; Xiongxiong Lu; Fanlu Li; Weishen Wang; Xiaomei Tang; Minmin Shi; Linxi Jiang; Hongwei Li; Hao Chen; Chenghong Peng; Zhiwei Xu; Xiaxing Deng; Baiyong Shen

doi:10.3389/fcell.2021.682261

Immunity-Related Gene Signature Identifies Subtypes Benefitting From Adjuvant Chemotherapy or Potentially Responding to PD1/PD-L1 Blockage in Pancreatic Cancer

Front Cell Dev Biol. 2021 Jun 23:9:682261. doi: 10.3389/fcell.2021.682261. eCollection 2021.

Authors

Hao Qian^{1

2}, Hongzhe Li^{1

2}, Junjie Xie^{1

2}, Xiongxiong Lu^{1

2}, Fanlu Li^{1

2}, Weishen Wang^{1

2}, Xiaomei Tang^{1

2}, Minmin Shi^{1

2}, Linxi Jiang^{1

2}, Hongwei Li^{1

2}, Hao Chen^{1

2}, Chenghong Peng^{1

2}, Zhiwei Xu^{1

2}, Xiaxing Deng^{1

2}, Baiyong Shen^{1

2

3

4}

Affiliations

¹ Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ State Key Laboratory of Oncogenes and Related Genes, Shanghai, China.
⁴ Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Tumor microenvironment comprises of a variety of cell types, which is quite complex and involved in chemotherapy and immune checkpoint blockage resistance. In order to explore the mechanisms involved in tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC), we first constructed an immunity-related 18-gene signature using The Cancer Genome Atlas (TCGA) PDAC project data. Then we applied the 18-gene signature to divide PDAC patients into low score and high score groups. Patients in high score group showed inferior prognosis, which was validated in another four independent cohorts, including Ruijin cohort. High score group showed significant enrichment of pathways involved in cell division and cell cycle especially in G1/S phase transition. In high score group, IHC analysis revealed higher levels of the proliferative indexes of Ki67 and PCNA than that in low score group. Prognostic analysis confirmed that patients in high score group could benefit from the gemcitabine-based adjuvant chemotherapy. In low score group, the programmed cell death 1 ligand 1(PD-L1) (+) cases showed worse prognosis but higher T cell infiltration than PD-L1(-) cases. Our immunity-related 18-gene signature could effectively predict PDAC prognosis, and it might be a practical predictive tool to identify PDAC subtype benefitting from gemcitabine-based adjuvant chemotherapy or potentially responding to PD1/PD-L1 blockade therapy.

Keywords: gene signature; immunity; pancreatic cancer; pancreatic ductal adenocarcinoma; prognosis.