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AIM To investigate the value of computed tomography (CT) texture analysis (TA) and imaging features for evaluating suspected surgical superior mesenteric–portal vein (SMPV) invasion in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS Fifty-four patients with PDAC in the pancreatic head or uncinate process with suspected SMPV involvement were analysed retrospectively. SMPV invasion status was identified by surgical exploration. For each patient, 396 texture features were extracted on pretreatment CT. Non-parametric tests and minimum redundancy maximum relevance were used for feature selection. A CTTA model was constructed using multivariate logistic regression, and the area under the receiver operating characteristic (AUROC) of the model was calculated. Two reviewers evaluated qualitative imaging features independently for SMPV invasion and interobserver agreement was investigated. The diagnostic performance of the imaging features and the CTTA model for SMPV invasion was compared using the McNemar test. RESULTS Of the 54 patients with PDAC, SMPV invasion was detected in 23 (42.6%). The CTTA model yielded an AUROC of 0.88 (95% confidence interval, 0.76–0.97) and achieved significantly higher specificity (0.90) than the two reviewers (0.61 and 0.65; p=0.027 and 0.043). Interobserver agreement was moderate between the two reviewers (κ = 0.517). Of the 13 cases with disagreement between the two reviewers, 11 cases were predicted accurately by the CTTA model. CONCLUSION CTTA can predict suspected SMPV invasion in PDAC and may be a beneficial addition for qualitative imaging evaluation.

Objectives To develop a radiomics signature for predicting surgical portal vein-superior mesenteric vein (PV-SMV) in patients with pancreatic ductal adenocarcinoma (PDAC) and measure the effect of providing the predictions of radiomics signature to radiologists with different diagnostic experiences during imaging interpretation. Methods Between February 2008 and June 2020, 146 patients with PDAC in pancreatic head or uncinate process from two institutions were retrospectively included and randomly split into a training (n = 88) and a validation (n =58) cohort. Intraoperative vascular exploration findings were used to identify surgical PV-SMV invasion. Radiomics features were extracted from the portal venous phase CT images. Radiomics signature was built with a linear elastic-net regression model. Area under receiver operating characteristic curve (AUC) of the radiomics signature was calculated. A senior and a junior radiologist independently review CT scans and made the diagnosis for PV-SMV invasion both with and without radiomics score (Radscore) assistance. A 2-sided Pearson's chi-squared test was conducted to evaluate whether there was a difference in sensitivity, specificity, and accuracy between the radiomics signature and the unassisted radiologists. To assess the incremental value of providing Radscore predictions to the radiologists, we compared the performance between unassisted evaluation and Radscore-assisted evaluation by using the McNemar test. Results Numbers of patients identified as presence of surgical PV-SMV invasion were 33 (37.5%) and 19 (32.8%) in the training and validation cohort, respectively. The radiomics signature achieved an AUC of 0.848 (95% confidence interval, 0.724-0.971) in the validation cohort and had a comparable sensitivity, specificity, and accuracy as the senior radiologist in predicting PV-SMV invasion (all p-values > 0.05). Providing predictions of radiomics signature increased both radiologists' sensitivity in identifying PV-SMV invasion, while only the increase of the junior radiologist was significant (63.2 vs 89.5%, p-value = 0.025) instead of the senior radiologist (73.7 vs 89.5%, p-value = 0.08). Both radiologists' accuracy had no significant increase when provided radiomics signature assistance (both p-values > 0.05). Conclusions The radiomics signature can predict surgical PV-SMV invasion in patients with PDAC and may have incremental value to the diagnostic performance of radiologists during imaging interpretation.

Background and aims Several studies were conducted to explore the prognostic value of platelet-to-lymphocyte ratio (PLR) in pancreatic cancer and have reported contradictory results. This study aims to summarize the prognostic role of PLR in pancreatic cancer. Materials and methods Embase, PubMed and Cochrane Library were completely searched. The cohort studies focusing on the prognostic role of PLR in pancreatic cancer were eligible. The overall survival (OS) and progression-free survival (PFS) were analyzed. Results Fifteen papers containing 17 cohort studies with pancreatic cancer were identified. The results showed patients that with low PLR might have longer OS when compared to the patients with high PLR (hazard ratio=1.28, 95% CI=1.17–1.40, P

Several studies were carried out to explore the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in pancreatic cancer, however, with contradictory results. The objectives of this study were to summarize the prognostic value of NLR in pancreatic cancer. Embase, PubMed and Cochrane Library were comprehensively retrieved. All the cohort studies focusing on the prognostic value of NLR in pancreatic cancer were eligible. 37 papers containing 43 cohort studies with pancreatic cancer were finally included into this study. The results presented that patients with low NLR might have longer OS when compared to the patients with high NLR (HR = 1.81, 95%CI = 1.59-2.05, P 0.00001; I

By investigating the migration and invasion ability in pancreatic cancer, this study probed into the lncRNA MALAT1 molecular mechanism on Hippo-YAP signaling. The expression of lncRNA MALAT1 in PC tissues and cells was detected by qRT-PCR and Western blot. The effect of si-MALAT1 on proliferation was determined by CCK-8 assay. Cell apoptosis, migration, and invasion were respectively detected by flow cytometry assay, wound healing assay, and transwell assay. Western blot and immunohistochemistry were successively used for detecting LATS1 and YAP1 expression in pancreatic cancer tissues. The microarray analysis determined that lncRNA MALAT1 in pancreatic cancer was highly expressed. LncRNA MALAT1 presented an extremely high expression level in pancreatic cancer tissues and cells. After transfected with si-MALAT1, the proliferation of AsPC-1 cells decreased, induce apoptosis of AsPC-1 cells, and migration and invasion ability were reduced. The tendency of LATS1 expression level was down-regulated and YAP1 show the opposite trend in the Hippo-YAP signaling. The in vivo assay was found that the tumor to be small in size and volume, and the expression of Ki-67 was decreased. High expression of lncRNA MALAT1 in PC disorder the proliferation, apoptosis, and migration and invasion ability via influence Hippo-YAP signaling pathway.

This study was expected to reveal the regulatory effects of lncRNA UCA1 on pancreatic cancer cell progression through targeting miR-96/FOXO3. Microarray analysis was carried out on 36 cases of pancreatic cancer tissues and 16 cases of adjacent tissues among them. Expression levels of lncRNA UCA1, miR-96, and FOXO3 in pancreatic cancer tissues and cell lines were determined by qRT-PCR. Expression levels of FOXO3 protein were determined by western blot. Cell viability, cell cycle and apoptosis, cell invasion and migration were detected by CCK-8, flow cytometry, and transwell assay, respectively. The colocalization relationship between lncRNA UCA1 and miR-96 was detected by RNA FISH. Whether UCA1 could target miR-96 and whether miR-96 could target FOXO3 3'UTR were verified by dual-luciferase reporter gene assay. High expression of lncRNA UCA1 and FOXO3 and low expression of miR-96 were shown in pancreatic cancer. Inhibition of UCA1 suppressed pancreatic tumor cell proliferation, colony formation, and metastasis, while inhibition of miR-96 promoted pancreatic cancer cell progression. FOXO3 was the downstream target gene of miR-96 and showed the opposite effects. LncRNA UCA1 promoted cell proliferation, invasion, migration and inhibited cell apoptosis of pancreatic cancer through down-regulating miR-96 and up-regulating FOXO3. © 2018 IUBMB Life, 70(4):276-290, 2018.

Drug resistance has always been an important problem affecting the therapeutic effect of hepatocellular carcinoma (HCC). To investigate the potential role of lncRNA TTN-AS1 in HCC cells with sorafenib (SOR) resistance, and explore the underlying pathways, quantitative real time polymerase chain reaction (qRT-PCR) was used to test the expression of TTN-AS1 in HCC tissues and cells. Then, the expression of TTN-AS1 was down-regulated by shRNA, the activity changes, apoptosis and related protein expression in HCC cells with/without SOR treatment were observed in succession. Expression levels of the downstream target of TTN-AS1, miR-16-5p were studied by dual-luciferase binding assay, cell proliferation, and western blotting analysis. Nude mice models of human HCC with TTN-AS1 gene knockdown were established to observe the tumor growth. As the results revealed, TTN-AS1 silencing in HCC cells induced apoptosis by enhancing the sensitivity of cells to SOR, and the tumor in nude mice became smaller. The mechanism study showed that miR-16-5p was affected by TTN-AS1 sponge, up-regulated cyclin E1 expression, and regulated PTEN/Akt signaling pathway, thereby significantly alleviating the inhibition of apoptosis of HCC cells induced by TTN-AS1 gene. Collectively, our results provided TTN-AS1 as a potential therapeutic target for sorafenib resistance in HCC.

BACKGROUND Many publications showed red blood cell distribution width (RDW) might associate with the prognosis of gastrointestinal (GI) cancers, however, the agreement has not been reached because of controversial results. This meta-analysis aimed to explore the prognostic value of RDW in GI cancers. METHODS Four common databases were comprehensively searched to look for relevant studies. The meta-analyses for overall survival (OS) and disease-free survival were performed using hazard ratio (HR) and 95% confidence interval (CI), and the meta-analyses for clinical parameters were conducted using odd ratio and 95% CI. RESULTS A total of 13 studies involving with 3,509 patients with GI cancers were included into this study. The results showed, compared to patients with low RDW, patients with high RDW tended to have shorter OS (HR = 1.75, 95%CI = 1.57-1.94, P

Long non-coding RNAs (lncRNAs) have been shown to play a significant role in the progression of many cancers, including pancreatic cancer (PC). However, the biological function and regulatory mechanisms of lncRNAs in PC remains largely unclear. The aim of this study was to identify and evaluate the potential functions of lncRNAs in PC and reveal the underlying mechanisms of their effects. Screening of published microarray data (GEO accession Nos. {"type":"entrez-geo","attrs":{"text":"GSE16515","term_id":"16515"}}GSE16515 and {"type":"entrez-geo","attrs":{"text":"GSE32688","term_id":"32688"}}GSE32688), revealed lncRNA AFAP1-AS1 to be one of the most upregulated lncRNAs in PC tissues. High expression of AFAP1-AS1 was correlated with advanced stages, tumor size and lymph node metastasis, as well as with poorer overall survival in patients with PC. Functionally, knockdown of AFAP1-AS1 by transfection with siRNA inhibited the proliferative and invasive capacities of PaCa-2 and SW1990 PC cells, promoted apoptosis of PC cells in vitro, and impaired in-vivo tumorigenicity. In particular, it was hypothesized that AFAP1-AS1 may act as a competitive endogenous RNA (ceRNA), effectively becoming a sink for miR-133a whose expression was found to be downregulated in PC tissues and cell lines, and which was negatively correlated with the expression of AFAP1-AS1. We also found that the IGF1R oncogene which is an important regulator of MEK/ERK signaling pathway, was positively regulated by AFAP1-AS1 through ameliorating miR-133a-mediated IGF1R repression in PC tissues. Moreover, we demonstrated that knockdown of IGF1R by transfection with si-IGF1R suppressed cell proliferation, invasion and migration of PaCa-2 and SW1990 PC cells, suggesting that IGF1R may function as an oncogene in PC cells. Further investigations revealed that miR-133a reversed the biological effects of AFAP1-AS1 on PC cells. Collectively, the findings provide new evidence that AFAP1-AS1 could regulate the progression of pancreatic cancer by acting as a ceRNA, and suggest it has potential for use as both a biomarker for the early detection PC and for the development of individualized therapies for PC.

Yongping Zhou,1 Sijin Cheng,2 Sinuo Chen,2 Yongzhao Zhao1,2 1Department of Hepatobiliary, Wuxi Second Hospital, Nanjing Medical University, Wuxi, People’s Republic of China; 2Tongji University School of Medicine, Shanghai, China Background: Several studies have explored the prognostic value of sirtuin 3 (SIRT3) in various cancers, but obtained inconsistent results. The current systematic review and meta-analysis was conducted to investigate the association between SIRT3 expression and prognosis in various cancers. Methods: PubMed, Embase, Web of Science and the Cochrane Library were comprehensively retrieved by the end of September 29, 2017. All the relevant studies were checked and included in the meta-analysis if they met the inclusion criteria. Results: A total of 17 studies involving 2,865 patients were included in the systematic review and meta-analysis. The results indicated that SIRT3 expression was not significantly associated with overall survival (OS) (hazard ratio [HR]=0.87, 95% CI=0.59–1.29,P=0.50) and disease-free survival (HR=0.87, 95% CI=0.57–1.31,P=0.50) in total various cancers. However, significant relationship between SIRT3 expression and OS in specific cancers was detected, including chronic lymphocytic leukemia (CLL) (HR=0.48, 95% CI=0.26–0.89, P=0.019), hepatocellular carcinoma (HCC) (HR=0.56, 95% CI=0.42–0.74,P

Backgrounds Plenty of studies have been conducted to explore the prognostic value of LncRNA AFAP1-AS1 in various cancers, however, with contradictory outcomes. The aim of the current study was to explore the prognostic value of high LncRNA AFAP1-AS1 expression in various cancers. Methods PubMed, EMBASE, Web of Science, Cochrane library, China National Knowledge Internet (CNKI) and Wan-fang database were comprehensively retrieved, and all the relevant studies were included into the study. Results A total of 21 studies involving 2179 patients were finally included into the systematic review and meta-analysis. Compared to low LncRNA AFAP1-AS1 expression, high LncRNA AFAP1-AS1 expression was significantly related to shorter OS (HR = 2.02, 95%CI = 1.51–2.70, P Conclusions Cancer patients with high LncRNA AFAP1-AS1 expression had shorter OS, DFS, RFS and PFS compared to those with low expression. Moreover, high LncRNA AFAP1-AS1 expression was significantly related to advanced clinical stage, larger tumor size, earlier tumor metastasis, earlier lymph nodal involvement and vascular invasion. High LncRNA AFAP1-AS1 expression was an unfavorable prognostic factor in various cancers.

// Yongping Zhou 1 , Yuxuan Lu 2 , Runmin Li 2 , Nana Yan 3 , Xiding Li 4 and Tu Dai 1 1 Department of Hepatobiliary, Wuxi Second Hospital, Nanjing Medical University, Wuxi, China 2 School of Medicine, Tongji University, Shanghai, China 3 Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China 4 Department of General Surgery, Wuxi Second Hospital, Nanjing Medical University, Wuxi, China Correspondence to: Tu Dai, email: 810704041@qq.com Xiding Li, email: lixiding007@163.com Keywords: long non-coding RNA TUG1, cancer, prognostic Received: May 10, 2017 Accepted: July 26, 2017 Published: August 08, 2017 ABSTRACT Several studies were conducted to explore the prognostic role of long non-coding RNA taurine upregulated gene 1 (lncRNA TUG1) expression in various cancers, with contradictory. This study aims to summarize the prognostic role of lncRNA TUG1 expression in various cancers. Embase, PubMed and Cochrane Library were completely retrieved. The cohort studies focusing on the prognostic role of lncRNA TUG1 expression in various cancers were eligible. The endpoints were overall survival (OS) and clinicopathological parameters. 9 studies involving a total of 1,078 patients were identified. The results showed that high lncRNA TUG1 expression was obviously associated with worse OS when compared to the low lncRNA TUG1 expression (HR = 1.37, 95% CI = 1.07–1.76, P = 0.01; I 2 = 85%). However, No distinct relationship was observed between the lncRNA TUG1 expression and age (OR = 0.99, 95% CI = 0.76–1.28, P = 0.92; I2 = 4%), gender (OR = 0.92, 95% CI = 0.70–1.22, P = 0.57; I 2 = 0%), diameter (OR = 0.83, 95% CI = 0.34–2.01, P = 0.67; I 2 = 85%), smoking (OR = 1.09, 95% CI = 0.37–3.21, P = 0.87; I 2 = 73%), TNM stage (OR = 0.60, 95% CI = 0.25–1.43, P = 0.25; I 2 = 86%) and lymph node metastasis (OR = 1.07, 95% CI = 0.47–2.45, P = 0.87; I 2 = 86%). In conclusion, it was revealed that high lncRNA TUG1 expression is an unfavorable predictor of OS in patients with cancers, and lncRNA TUG1 expression is a promising prognostic biomarker for various cancers.