Abstract

BackgroundLong noncoding RNAs (lncRNAs) have recently been known to play various important roles in maintaining molecular regulations. Significant amounts of lncRNAs HOTTIP, PVT1 and H19 are well known to be expressed in pancreatic cancer cells, however their association with efficacy of adjuvant chemotherapy for pancreatic cancer have not been fully investigated. The aim of this study was to evaluate expression of HOTTIP, PVT1 and H19 in the pancreatic cancer cells, and to clarify the predictive roles of those lncRNAs in pancreatic cancer patients who received adjuvant chemotherapy by S-1, an oral fluoropyrimidine or gemcitabine (GEM) after curative resection. MethodsPancreatic cancer patients who underwent curative resection followed by adjuvant chemotherapy by S-1 or GEM since 2005 to 2017 at Kanagawa Cancer Centre were enrolled in this study. In situ hybridization (RNA scope®) to detect each three lncRNAs was performed using tissue microarrays prepared from formalin-fixed and paraffin-embedded tissues of resected specimens. The relations between the expression of HOTTIP, PVT1 and H19 and clinicopathological characteristics were statistically analyzed. ResultsWe analyzed 204 eligible pancreatic cancer patients. 114 patients received adjuvant chemotherapy by S-1, and 90 patients by GEM. The patients with higher expression of H19 were significantly associated with shorter relapse free survival (RFS) regardless of adjuvant chemotherapy regimens (p<0.01). Contrary, the patients with higher expression of PVT1 were significantly associated with longer RFS when they were received adjuvant chemotherapy with S-1 (p=0.048), but not with GEM (p=0.65). The patients with higher expression of HOTTIP were significantly associated with longer overall survival (OS) in the GEM group (p<0.01), and not in the S-1 group (p=0.38). ConclusionsThe expression levels of PVT1 and HOTTIP in pancreatic cancer cells were associated with the efficacy of adjuvant chemotherapy for pancreatic cancer in the present study. The higher expression of H19 may serve as a significant predictive/prognostic marker for patients who received adjuvant chemotherapy by S-1 or GEM after curative resection. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

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