Pancreatic cancer is typically not diagnosed until the patient seeks medical treatment after having experienced symptoms including abdominal pain, weight loss, itching, and jaundice for weeks or months. At this point, diagnosis is relatively straightforward using imaging and biopsy techniques, but a cure is unlikely as the cancer is already quite advanced. Identifying early markers of pancreatic cancer is a priority for oncology researchers as early detection of the disease is critical to improving patient survival rates.
Novel 5-gene PDAC classifier
Recently, researchers conducted a meta-analysis of applicable studies related to the pancreatic ductal adenocarcinoma (PDAC) transcriptome in order to identify key biomarkers. Expression of a 5-gene biomarker panel was identified by qRT-PCR in microdissected PDAC patient-derived formalin-fixed, paraffin embedded (FFPE) tissues. Five genes (TMPRSS4, AHNAK2, POSTN, ECT2, SERPINB5) showed 95% sensitivity and 89% specificity in discriminating PDAC from non-tumor samples from humans as well as in specific mouse models of disease. Moreover, the 5-gene classifier panel was able to discriminate PDAC tissue from matched surrounding non-tumor tissue in FFPE samples from the same patients. This study identified a highly accurate 5-gene PDAC classifier that is capable of discriminating early PDAC lesions from non-malignant tissue and may, therefore, facilitate early diagnosis for some patients. Further studies are needed to investigate a putative causal link between these genes and PDAC.
DNA repair susceptibility genes
DNA repair genes are known to play a role in gastrointestinal malignancies including PDAC. A recent study asked whether some DNA repair genes might be functioning as PDAC susceptibility genes. Considering overall survival as their primary endpoint, the researchers identified 513 putative DNA repair genes carrying rare protein-truncating variants in the germline exomes of 109 high-risk PDAC cases. Analysis of DNA extracted from fresh-frozen tissue and FFPE tissue blocks revealed that the strongest candidates were FAN1, NEK1, and RHNO1; with overall survival being significantly less in carriers of these variants than in non-carriers. This study established that patients with early stage PDAC disease who are carriers of a germline protein-truncating variant in certain DNA repair genes have the worst chances of survival. This information can help doctors and patients identify the correct treatment strategy for pancreatic cancer at an early stage.
Differential expression of miRNAs
MicroRNAs (miRNAs) are small, non-coding RNA sequences that have been implicated in gene silencing and post-transcriptional regulation of genes in many cancers, and they remain an active area of oncology research for their potential therapeutic capabilities. Scientists investigating the role of miRNAs in pancreatic cancer specifically observed differential expression between healthy and tumor tissues. Comparing the expression profile of miRNAs in FFPE tissues extracted from pancreatic cancer tumor samples and healthy controls to a miRNA archive database (miRBase), investigators isolated 7 selected miRNAs for further analysis by qRT-PCR. The following miRNAs showed a significant difference between healthy and tumor tissue samples: miR-21, miR-205, miR-155, miR-31, miR-203, miR-214 and miR-129-2. In addition, overall survival was negatively correlated with miR-214 expression. Although further investigation is needed to investigate the potential signaling role of these differentially expressed miRNAs in pancreatic cancer, they may provide reliable early biomarkers of disease and even predict overall survival for patients.
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