title: Linc00675 is a novel marker of short survival and recurrence in patients with pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  To detect linc00675 expression in pancreatic ductal adenocarcinoma (PDAC), to analyze the relationship between the expression level of linc00675 and the clinical pathological characteristics, to explore the biological functions of linc00675, and to determine whether linc00675 has independent prognostic value in PDAC.
  
  
  METHODS
  We studied linc00675 expression among eight histologically confirmed PDAC tissue samples and four chronic pancreatitis tissue samples through microarray screening. RT-qPCR was conducted to further investigate linc00675 expression in PDAC cell lines as well as archived tissues from a large cohort of PDAC patients. The correlations between the level of lnc00675 and clinicopathological characteristics and survival in patients with pancreatic cancer were evaluated using Correlation analysis. Univariate and multivariate analyses were conducted to predict whether lnc00675 expression is an independent prognostic and recurrence factor in patients with pancreatic cancer. After downregulating the expression of linc00675 through siRNA, MTT assay, flow cytometry, transwell assay and Western blot were used to explore the biological function of linc00675 in proliferation, invasion, and cell cycle progression of pancreatic cancer cells. The relative molecular expression levels of epithelial-mesenchymal transition were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.
  
  
  RESULTS
  The expression of Linc00675 in PDAC tissue samples was shown to be 672 times that in chronic pancreatitis tissue samples by microarray screening (P = 3.69 × 10(-5)). This finding was confirmed in tumor tissues from 90 patients with PDAC compared with adjacent normal tissue samples by quantitative RT-PCR. We found that linc00675 overexpression positively correlated with lymph node metastasis (P = 0.005), perineural invasion (P = 0.006), and poor survival (P < 0.001). Univariate and multivariate analyses showed that linc00675 expression served as an independent predictor of overall survival (P = 0.009). Additionally, receiver operating characteristic curve analysis showed that high linc00675 might serve as a predictor of tumor progression within 6 mo to a year after surgery. In vitro functional analysis demonstrated that knockdown of linc00675 attenuated pancreatic cancer cell proliferation and invasion as well as induced S phase arrest. Suppression of linc00675 in pancreatic cancer cells resulted can reverse the progress of epithelial-mesenchymal transition.
  
  
  CONCLUSIONS
  Linc00675 may function as an oncogene during PDAC development, and its expression is an independent predictor of unfavorable prognosis in patients with PDAC.
authors: Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors: Dou-Dou
authors: DD
authors: Li
authors: Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors: Zhi-Qiang
authors: ZQ
authors: Fu
authors: Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors: Qing
authors: Q
authors: Lin
authors: Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors: Yu
authors: Y
authors: Zhou
authors: Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors: Quan-Bo
authors: QB
authors: Zhou
authors: Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors: Zhi-Hua
authors: ZH
authors: Li
authors: Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors: Lang-Ping
authors: LP
authors: Tan
authors: Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors: Ru-Fu
authors: RF
authors: Chen
authors: Dou-Dou Li, Yi-Min Liu, Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China.
authors: Yi-Min
authors: YM
authors: Liu
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000556:secondary / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012372:ROC Curve; D012307:Risk Factors; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; C000611370:long non-coding RNA Linc00675, human
keywords: Epithelial-mesenchymal transition; Linc00675; Long noncoding RNAs; Pancreatic cancer; Prognosis biomarker