MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation

<p>Abstract</p> <p>Background</p> <p>Recently, the microRNA-200 family was reported to affect cancer biology by regulating epithelial to mesenchymal transition (EMT). Especially, the expression of <it>miR-200c </it>has been shown to be associated with upregulating the expression of <it>E-cadherin</it>, a gene known to be involved in pancreatic cancer behavior. However, the significance of <it>miR-200c </it>in pancreatic cancer is unknown.</p> <p>Methods</p> <p>In the present study, we investigated the relationship between <it>E-cadherin </it>and <it>miR-200c </it>expression in a panel of 14 pancreatic cancer cell lines and in macro-dissected formalin-fixed paraffin-embedded (FFPE) tissue samples obtained from 99 patients who underwent pancreatectomy for pancreatic cancer. We also investigated the effects of <it>miR-200c </it>on the proliferation and invasion of pancreatic cancer cells.</p> <p>Results</p> <p>We found that patients with high levels of <it>miR-200c </it>expression had significantly better survival rates than those with low levels of <it>miR-200c </it>expression. We also found a remarkably strong correlation between the levels of <it>miR-200c </it>and <it>E-cadherin </it>expression.</p> <p>Conclusions</p> <p>These data indicate that <it>miR-200c </it>may play a role in the pancreatic cancer biology and may be a novel marker for the prognosis of pancreatic cancer.</p

Gene Expression Levels as Predictive Markers of Outcome in Pancreatic Cancer after Gemcitabine-Based Adjuvant Chemotherapy12

AbstractBACKGROUND AND AIMS: The standard palliative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) is gemcitabine-based chemotherapy; however, PDAC still presents a major therapeutic challenge. The aims of this study were to investigate the expression pattern of genes involved in gemcitabine sensitivity in resected PDAC tissues and to determine correlations of gene expression with treatment outcome. MATERIALS AND METHODS: We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 70 patients with PDAC. Of the 70 patients, 40 received gemcitabine-based adjuvant chemotherapy (AC). We measured hENT1, dCK, CDA, RRM1, and RRM2 messenger RNA (mRNA) levels by quantitative real-time reverse transcription-polymerase chain reaction and determined the combined score (GEM score), based on the expression levels of hENT1, dCK, RRM1, and RRM2, to investigate the association with survival time. By determining the expression levels of these genes in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytologic specimens, we investigated the feasibility of individualized chemotherapy. RESULTS: High dCK (P = .0067), low RRM2 (P = .003), and high GEM score (P = .0003) groups had a significantly longer disease-free survival in the gemcitabine-treated group. A low GEM score (<2) was an independent predictive marker for poor outcome to gemcitabine-based AC as shown by multivariate analysis (P = .0081). Altered expression levels of these genes were distinguishable in microdissected neoplastic cells from EUS-FNA cytologic specimens. CONCLUSIONS: Quantitative analyses of hENT1, dCK, RRM1, and RRM2 mRNA levels using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytologic specimens may be useful in predicting the gemcitabine sensitivity of patients with PDAC