Gene expression profiling of pancreatic ductal adenocarcino…

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all major cancers. Chemotherapy is the mainstay systemic therapy for PDAC, and chemoresistance is a major clinical problem leading to therapeutic failure. This study aimed to identify key differences in gene expression profile in tumors from chemoresponsive and chemoresistant patients. Archived formalin-fixed paraffin-embedded tumor tissue samples from patients treated with neoadjuvant chemotherapy were obtained during surgical resection. Specimens were macrodissected and gene expression analysis was performed. Multi- and univariate statistical analysis was performed to identify differential gene expression profile of tumors from good (0%-30% residual viable tumor [RVT]) and poor (>30% RVT) chemotherapy-responders. Initially, unsupervised multivariate modeling was performed by principal component analysis, which demonstrated a distinct gene expression profile between good- and poor-chemotherapy responders. There were 396 genes that were significantly (p < 0.05) downregulated (200 genes) or upregulated (196 genes) in tumors from good responders compared to poor responders. Further supervised multivariate analysis of significant genes by partial least square (PLS) demonstrated a highly distinct gene expression profile between good- and poor responders. A gene biomarker of panel (IL18, SPA17, CD58, PTTG1, MTBP, ABL1, SFRP1, CHRDL1, IGF1, and CFD) was selected based on PLS model, and univariate regression analysis of individual genes was performed. The identified biomarker panel demonstrated a very high ability to diagnose good-responding PDAC patients (AUROC: 0.977, sensitivity: 82.4%; specificity: 87.0%). A distinct tumor biological profile between PDAC patients who either respond or not respond to chemotherapy was identified.

Keywords

biomarkers chemotherapy response gene expression analysis neoadjuvant chemotherapy pancreatic ductal adenocarcinoma

MeSH 主题词

Humans Neoadjuvant Therapy Carcinoma, Pancreatic Ductal/drug therapy,genetics,metabolism Pancreatic Neoplasms/drug therapy,genetics,metabolism Gene Expression Profiling Biomarkers Biomarkers, Tumor/genetics,metabolism

化学物质

Biomarkers Biomarkers, Tumor

作者与单位

共 12 位作者，点击展开单位 / ORCID

Sahni Sumit ORCID

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia. | Australian Pancreatic Centre, Sydney, New South Wales, Australia.

Nahm Christopher

Western Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia.

Ahadi Mahsa S

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia. | Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.

Sioson Loretta

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia. | Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.

Byeon Sooin

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia.

Chou Angela

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia. | Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.

Maloney Sarah

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia.

Moon Elizabeth

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia.

Pavlakis Nick

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia. | Northern Sydney Cancer Center, Royal North Shore Hospital, St Leonards, New South Wales, Australia. | Northern Cancer Institute, St Leonards, New South Wales, Australia.

Gill Anthony J

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia. | Department of Anatomical Pathology, NSW Health Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.

Samra Jaswinder

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia. | Australian Pancreatic Centre, Sydney, New South Wales, Australia. | Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, New South Wales, Australia.

Mittal Anubhav

Northern Clinical School, Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia. | Northern Clinical School, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia. | Australian Pancreatic Centre, Sydney, New South Wales, Australia. | Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, New South Wales, Australia. | The University of Notre Dame Australia, Sydney, New South Wales, Australia.

Gene expression profiling of pancreatic ductal adenocarcinomas in response to neoadjuvant chemotherapy.

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