Abstract
Pancreatic ductal adenocarcinoma (PDAC) death rate and recurrence rate have remained obstinately high. Current methods can not satisfy the need of predicting cancer relapse accurately. Utilizing expression profiles of 10 GEO datasets (N = 774), we identified 154 differentially expressed genes (DEGs) between PDAC and normal pancreas tissue or paracancerous tissue. Next we built a 16-mRNA-based signature by means of the LASSO COX regression model. We also validated the prognostic value of the signature. Patients were classified into high-risk and low-risk group according to the signature risk score; 1 year RFS was 45% (95% CI: 31.6%–63.9%) for high-risk group in contrast to 92.5% (95% CI: 86.3%–99.1%) for low-risk group. Moreover, it could predict RFS well in cases with the receipt of different treatment modalities. The 16-mRNA-based signature was an independent and powerful prognostic biomarker for RFS for PDAC patients (HR = 7.74, 95% CI: 3.25–18.45, p < 0.0001).
Highlights
Pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of pancreatic cancer (PC), which is the third leading cause of cancer mortality followed by lung cancer and colorectal cancer [1]. 5 year overall survival (OS) for PC has increased slightly from 5% to 8% and more than 52% cases are initially diagnosed at a distant stage for which 5 year OS is only 3% [1].The main reasons include the shortcomings of effective therapies and the lack of specific biomarkers or clinical symptoms in diagnosis
Metabolic process was the main term of biological processes (BP), while terms associated with collagen and extracellular matrix (ECM) were enriched in cellular component (CC)
To verify that 16-Messeger RNAs (mRNAs)-based signature had an excellent prognostic value, COX univariable analysis of 20 clinical factors and the signature with Relapse-free survival (RFS) were conducted. It demonstrated that 16-mRNA-based signature, histologic grade, N stage, T stage, primary therapy outcome success and AJCC8 N stage were significantly related to RFS
Summary
PDAC accounts for approximately 90% of pancreatic cancer (PC), which is the third leading cause of cancer mortality followed by lung cancer and colorectal cancer [1]. 5 year overall survival (OS) for PC has increased slightly from 5% to 8% and more than 52% cases are initially diagnosed at a distant stage for which 5 year OS is only 3% [1].The main reasons include the shortcomings of effective therapies and the lack of specific biomarkers or clinical symptoms in diagnosis.Many therapeutic fields have emerged for decades, such as surgery, postoperative adjuvant chemoradiotherapy, targeted molecular therapy (TMT), neo-adjuvant chemotherapy, immunotherapy, and therapeutic exosomes or microvesicles.Surgical resection is still the only potentially curative therapy. 5 year overall survival (OS) for PC has increased slightly from 5% to 8% and more than 52% cases are initially diagnosed at a distant stage for which 5 year OS is only 3% [1].The main reasons include the shortcomings of effective therapies and the lack of specific biomarkers or clinical symptoms in diagnosis. Many therapeutic fields have emerged for decades, such as surgery, postoperative adjuvant chemoradiotherapy, targeted molecular therapy (TMT), neo-adjuvant chemotherapy, immunotherapy, and therapeutic exosomes or microvesicles. Surgical resection is still the only potentially curative therapy. Less than 20% have a surgical opportunity and over one-half of cases experience a postoperative relapse [2]. Cancer relapse directly results in shorter survival time after operation. Adjuvant chemotherapy with gemcitabine has been a standard care for resected PC which can delay recurrence [3]
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