Integrated chromosomal instability and tumor microbiome redefined prognosis-related subtypes of pancreatic cancer

Rui-Han Chen; Jia-Ying Cao; Shi Feng; Hai-Tao Huang; Yi-Mou Lin; Jing-Yu Jiang; Xue-Wen Yi; Qi Ling

doi:10.1016/j.hbpd.2024.03.002

Integrated chromosomal instability and tumor microbiome redefined prognosis-related subtypes of pancreatic cancer

Hepatobiliary Pancreat Dis Int. 2024 Mar 19:S1499-3872(24)00041-9. doi: 10.1016/j.hbpd.2024.03.002. Online ahead of print.

Authors

Rui-Han Chen¹, Jia-Ying Cao¹, Shi Feng², Hai-Tao Huang³, Yi-Mou Lin¹, Jing-Yu Jiang¹, Xue-Wen Yi¹, Qi Ling⁴

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China.
² Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
³ Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Department of Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
⁴ Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. Electronic address: lingqi@zju.edu.cn.

PMID: 38556382
DOI: 10.1016/j.hbpd.2024.03.002

Abstract

Background: Pancreatic cancer is a common malignancy with poor prognosis and limited treatment. Here we aimed to investigate the role of host chromosomal instability (CIN) and tumor microbiome in the prognosis of pancreatic cancer patients.

Methods: One hundred formalin-fixed paraffin-embedded (FFPE) pancreatic cancer samples were collected. DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing (WGS) via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detector.

Results: Samples are tested according to the procedure of ultrasensitive chromosomal aneuploidy detector (UCAD). We excluded 2 samples with failed quality control, 1 patient lost to follow-up and 6 dead in the perioperative period. The final 91 patients were admitted for the following analyses. Thirteen (14.3%) patients with higher CIN score had worse overall survival (OS) than those with lower CIN score. The top 20 microbes in pancreatic cancer samples included 15 species of bacteria and 5 species of viruses. Patients with high human herpesvirus (HHV)-7 and HHV-5 DNA reads exhibited worse OS. Furthermore, we classified 91 patients into 3 subtypes. Patients with higher CIN score (n =13) had the worst prognosis (median OS 6.9 mon); patients with lower CIN score but with HHV-7/5 DNA load (n = 24) had worse prognosis (median OS 10.6 mon); while patients with lower CIN score and HHV-7/5 DNA negative (n = 54) had the best prognosis (median OS 21.1 mon).

Conclusions: High CIN and HHV-7/5 DNA load were associated with worse survival of pancreatic cancer. The novel molecular subtypes of pancreatic cancer based on CIN and microbiome had prognostic value.

Keywords: Chromosomal instability; Microbiome; Molecular subtype; Pancreatic cancer.