metallothionein and Carcinoma--Pancreatic-Ductal

The low survival of patients with pancreatic ductal adenocarcinoma (PDAC) makes the treatment of this disease one of the most challenging task in modern medicine. Here, by mining a large-scale cancer genome atlas data set of pancreatic cancer tissues, we identified 21 long noncoding RNAs (lncRNAs) that significantly associated with overall survival in patients with PDAC (P < .01). Further analysis revealed that 8 lncRNAs turned out to be independently correlated with patients' overall survival, and the risk score could be calculated based on their expression. To obtain a better predicting power, we integrated lncRNA data with a total of 410 differently expressed messenger RNAs (mRNAs) screened from PDAC and normal tissues in gene expression omnibus (GEO) database. The integration resulted in a much better panel including 8 lncRNAs (RP3.470B24.5, CTA.941F9.9, RP11.557H15.3, LINC00960, AP000479.1, LINC00635, LINC00636, and AC073133.1) and 8 mRNAs (DHRS9, ONECUT1, OR8D4, MT1M, TCN1, MMP9, DPYSL3, and TTN) to predict prognosis. A functional evaluation showed that these lncRNAs might play roles in pancreatic secretion, cell adhesion, and proteolysis. Using normal and pancreatic cancer cell lines, we confirmed that a majority of identified lncRNAs and mRNAs showed altered expressions in pancreatic cancer cells. Especially, LINC01589, LINC00960, TCN1, and MT1M showed a profoundly increased expression in pancreatic cancer cells, which suggests their potentially important role in pancreatic cancer. The results of our work indicate that lncRNAs have vital roles in PADC and provide new insights to integrate multiple kinds of markers in clinical practices.

Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Data Mining; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Metallothionein; Oligonucleotide Array Sequence Analysis; Pancreatic Neoplasms; Prognosis; RNA, Long Noncoding; RNA, Messenger; Survival Analysis

Lumican, a member of the class II small leucine-rich proteoglycan family, regulates the assembly and diameter of collagen fibers in the extracellular matrix of various tissues. We previously reported that lumican expression in the stromal tissues of pancreatic ductal adenocarcinoma (PDAC) correlates with tumor invasion, and tends to correlate with poor prognosis. Lumican stimulates growth and inhibits the invasion of a PDAC cell line. In the present study, we performed a global shotgun proteomic analysis using lumican-overexpressing PANC‑1 cells and lumican downregulated PANC‑1 cells to identify candidate proteins that are regulated by lumican and related to cell growth and invasion in PDAC cells. A total of 448 proteins were identified from lumican-overexpressing PANC‑1 and control cells. Additionally, 451 proteins were identified from lumican-downregulated PANC‑1 cells and control cells. As a result of semi-quantification based on spectral counting, 174 differentially expressed proteins were identified by lumican upregulation, and 143 differentially expressed proteins were identified by lumican downregulation. The expression levels of 24 proteins, including apoptosis- and invasion-related proteins correlated with lumican expression levels. It is likely that the expression of these proteins is regulated by lumican, and that they are involved in apoptosis and invasion in PDAC. These findings suggest that lumican may be involved in cell growth and invasion through the regulation of these 24 proteins expressed in PDAC.

Topics: Apoptosis; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Cell Proliferation; Chondroitin Sulfate Proteoglycans; Down-Regulation; Gene Expression; Humans; Keratan Sulfate; Lumican; Metallothionein; Neoplasm Invasiveness; Pancreatic Neoplasms; Prognosis; Protein Isoforms; Proteomics; Up-Regulation