Linc00675 is a novel marker of short survival and recurrence in patients with pancreatic ductal adenocarcinoma

Dou-Dou Li, Zhi-Qiang Fu, Qing Lin, Yu Zhou, Quan-Bo Zhou, Zhi-Hua Li, Lang-Ping Tan, Ru-Fu Chen, Yi-Min Liu
World Journal of Gastroenterology: WJG 2015 August 21, 21 (31): 9348-57

AIM: 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.

CONCLUSION: Linc00675 may function as an oncogene during PDAC development, and its expression is an independent predictor of unfavorable prognosis in patients with PDAC.

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