Deeper insights into long-term survival heterogeneity of Pancreatic Ductal Adenocarcinoma (PDAC) patients using integrative individual- and group-level transcriptome network analyses

SummaryBackgroundPancreatic ductal adenocarcinoma (PDAC) is categorized as the seventh leading cause of cancer mortality worldwide. Its predictive markers for long-term survival are not well known. Therefore, it is interesting to delineate individual-specific perturbed genes when comparing long-term (LT) and short-term (ST) PDAC survivors, and to exploit the integrative individual- and group-based transcriptome profiling.MethodUsing a discovery cohort of 19 PDAC patients from CHU-Liège (Belgium), we first performed differential gene expression (DGE) analysis comparing LT to ST survivor. Second, we adopted unsupervised systems biology approaches to obtain gene modules linked to clinical features. Third, we created individual-specific perturbation profiles and identified key regulators across the LT patients. Furthermore, we applied two gene prioritization approaches: random walk-based Degree-Aware disease gene prioritizing (DADA) method to develop PDAC disease modules; Network-based Integration of Multi-omics Data (NetICS) to integrate group-based and individual-specific perturbed genes in relation to PDAC LT survival.FindingsWe identified 173 differentially expressed genes (DEGs) in ST and LT survivors and five modules (including 38 DEGs) showing associations to clinical traits such as tumor size and chemotherapy. DGE analysis identified differences in genes involved in metabolic and cell cycle activity. Validation of DEGs in the molecular lab suggested a role of REG4 and TSPAN8 in PDAC survival. Individual-specific omics changes across LT survivors revealed biological signatures such as focal adhesion and extracellular matrix receptors, implying a potential role in molecular-level heterogeneity of LT PDAC survivors. Via NetICS and DADA we not only identified various known oncogenes such as CUL1, SCF62, EGF, FOSL1, MMP9, and TGFB1, but also highlighted novel genes (TAC1, KCNH7, IRS4, DKK4).InterpretationOur proposed analytic workflow shows the advantages of combining clinical and omics data as well as individual- and group-level transcriptome profiling. It suggested novel potential transcriptome marks of LT survival heterogeneity in PDAC.FundingTélévie-FRS-FNRS

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Vascular resection for locally advanced pancreatic ductal adenocarcinoma: analysis of long-term outcomes from a single-centre series

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02238-x ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Claudio F. Feo ◽

Giulia Deiana ◽

Chiara Ninniri ◽

Giuseppe Cherchi ◽

Paola Crivelli ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Locally Advanced ◽

Operating Time ◽

Vascular Resection ◽

Ductal Adenocarcinoma ◽

Term Survival ◽

Aggressive Approach ◽

Long Term Survival ◽

Cox Regression Analysis

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Radical surgery is the best option for cure and, nowadays, it is performed by many surgeons also in cases of vascular infiltration. Whether this aggressive approach to a locally advanced PDAC produces a survival benefit is under debate. Most data in the literature come from retrospective comparative studies; therefore, it is still unclear if such an extensive surgery for an advanced cancer is justified. Methods A retrospective review of patients with PDAC treated at our institution over a 12-year period was performed. Data concerning patients’ characteristics, operative details, postoperative course, and long-term survival were retrieved from prospective databases and analysed. Factors associated with poor survival were assessed via Cox regression analysis. Results A total of 173 patients with PDAC were included in the analysis, 41 subjects underwent pancreatectomy with vascular resection for locally advanced disease, and in 132 patients, only a pancreatic resection was undertaken. Demographics, major comorbidities, and tumour characteristics were similar between the two groups. Length of surgery (P=0.0006), intraoperative blood transfusions (P<0.0001), and overall complications (P<0.0001) were significantly higher in the vascular resection group. Length of hospital stay (P=0.684) and 90-day mortality (P=0.575) were comparable between groups. Overall median survival (P= 0.717) and survival rates at 1, 3, and 5 years (P=0.964, P=0.500, and P=0.445, respectively) did not differ significantly between groups. Age ≥70 years and postoperative complications were independent predictors of lower survival. Conclusions Our study confirms that pancreatectomy with vascular resection for a locally advanced PDAC is a complex operation associated with a significant longer operating time that may increase morbidity; however, in selected patients, R0 margins can be obtained with an acceptable long-term survival rate. Older patients are less likely to benefit from surgery.

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Survival and quality of life following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma

International Journal of Cancer Research & Therapy ◽

10.33140/ijcrt.06.02.07 ◽

2021 ◽

Vol 6 (2) ◽

Keyword(s):

Quality Of Life ◽

Pancreatic Ductal Adenocarcinoma ◽

Short Review ◽

Mortality Rates ◽

Ductal Adenocarcinoma ◽

Term Survival ◽

Long Term Survival ◽

Dismal Prognosis

Pancreatic ductal adenocarcinoma (PDAC) most commonly affects the head of the pancreas. This condition has a dismal prognosis. Patients with early disease may be candidates for pancreaticoduodenectomy (PD). This is a high-risk operation which is associated with considerable morbidity. Whilst perioperative mortality rates have fallen in recent times, the risk remains significant and long-term survival is poor, even in those who make an uncomplicated recovery. Furthermore, PD is known to affect quality of life (QoL) negatively. Most studies suggest it takes up to six months before a patient’s QoL returns to baseline. This is a considerable amount of time for a patient who is unlikely to achieve long-term survival. This short review discusses the recent literature surrounding mortality rates, long-term survival and QoL following PD for PDAC. A comprehensive understanding of these topics will allow clinicians and patients to consider the risks and benefits before surgical resection is considered.

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