Orchestrating a biomarker panel with lncRNAs and mRNAs for predicting survival in pancreatic ductal adenocarcinoma

Abstract

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.

LINC00636 promotes lymph node metastasis and cervical cancer through targeting NM23

“…However, the mechanisms of LINC00636 elevation in patients with metastatic cervical cancer needs further study. Previous studies found that LINC00636 is up-regulated in human epidermal growth factor receptor-2 (HER-2) highly expressed breast cancer subtype [ 25 ] and pancreatic ductal adenocarcinoma [ 26 ] and could be the indicator of prognosis, which are consistent with results in this study.…”

High expression of TCN1 is a negative prognostic biomarker and can predict neoadjuvant chemosensitivity of colon cancer

“…Lee et al found that overexpression of TCN1 in rectal cancer was related to advanced pre-/post-treatment tumour status, nodal status, vascular invasion, and tumour regression grade 21 . Wu et al also reported that TCN1 was highly expressed in pancreatic cancer 26 and Chu et al found it had a role in tumour invasion and metastasis, which were all consistent with our findings.…”

Exosomes and Hepatocellular Carcinoma: From Bench to Bedside

“…Xu et al investigated serum exosomal lncRNA ENSG00000258332.1 (LINC02394) and LINC00635 in experiments by comparing the sera between 55 HCC patients, 60 chronically HBV-infected patients and 60 healthy controls for the purpose of identifying potential diagnostic markers and prediction markers for the prognosis of HCC [93]. LINC00635 has been reported to predict the survival in patients with pancreatic ductal adenocarcinoma [94]. Both lncRNA ENSG00000258332.1 and LINC00635 levels in the HCC group were significantly higher than those in the other groups.…”

“…Exosomes may be potential biomarkers for predicting survival in HCC patients (Table 2) [8,30,35,45,46,47,73,79,80,81,82,85,89,93,94,95,107]. Exosomal circular RNA PTGR1 (circPTGR1) is up-regulated in HCC and the expression of exosomal circPTGR1 is associated with poor outcomes for patients with HCC [107].…”