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

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外文标题：Integrated chromosomal instability and tumor microbiome redefined prognosis-related subtypes of pancreatic cancer

外文摘要：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 col-lected.DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing(WGS)via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detec-tor.Results:Samples were tested according to the procedure of ultrasensitive chromosomal aneuploidy detec-tor(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.Pa-tients 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 prog-nosis(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.

外文关键词：

Pancreatic cancerChromosomal instabilityMicrobiomeMolecular subtype

作者：

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

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作者单位：

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 Pathology,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China

Department of Surgery,Shanghai Tenth People's Hospital,Tongji University School of Medicine,Shanghai 200072,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,Hangzho

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关键词：

Pancreatic cancer Chromosomal instability Microbiome Molecular subtype

出版年：

2024

DOI：

10.1016/j.hbpd.2024.03.002

国际肝胆胰疾病杂志(英文版)

浙江省医学学术交流管理中心,浙江大学医学院附属第一医院,浙江大学出版社有限责任公司

国际肝胆胰疾病杂志(英文版)

影响因子：0.668

ISSN：1499-3872

年,卷(期)：2024.23(6)