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Objiective: Our study aimed to assess the ability of High-Sensitivity modified Glasgow Prognostic Score (HS-mGPS) predicting survival in patients undergoing radical surgery for hepatocellular carcinoma (HCC) and to compare the impact with other Inflammation-Based Prognostic Scoring systems including Glasgow Prognostic Score (GPS) and modified GPS (mGPS). Methods: Our study evaluated 293 patients with HCC who had undergone hepatectomy at the Third Affiliated Hospital of Soochow University between 2010 and 2018. The HS-mGPS, mGPS, and GPS were calculated based on particular cut-off values of preoperative C-reactive protein and albumin, and the correlations between HS-mGPS and clinicopathological parameters were evaluated. Univariate and multivariate survival analyses were conducted by Kaplan–Meier method and Cox proportional hazards model. Result: Kaplan-Meier and univariate survival analyses demonstrated that higher scores of the HS-mGPS, GPS and mGPS were all associated with significantly lower overall survival (OS) (all p < 0.001). In multivariate survival analysis, the HS-mGPS (p = 0.010) was an independent risk factor for poor OS in patients with HCC undergoing hepatectomy, along with the maximal tumor diameter (p < 0.001), microvascular invasion(MVI)( p = 0.008), and BCLC stage(p = 0.001). Based on the receiver operating characteristic (ROC) curve and AUC (areas under the curve) values, HS-mGPS was superior to GPS and mGPS for predicting the long-term prognosis of patients with resectable HCC. Conclusion: Preoperative HS-mGPS is a superior prognostic score in predicting poor long-term outcomes after HCC patients undergoing radical surgery.

Purpose: Investigate the role of regulator of chromosome condensation 2 (RCC2) on lung adenocarcinoma (LUAD) metastasis.Experimental Design: Clinical specimens were used to assess the impact of RCC2 on LUAD metastasis. Mouse models, cytobiology, and molecular biology assays were performed to elucidate the function and underlying mechanisms of RCC2 in LUAD.Results: RCC2 expression was frequently increased in LUADs (88/122, 72.13%). It was confirmed by analysis of a larger cohort of TCGA RNA-seq data containing 488 LUADs and 58 normal lung tissues (P < 0.001). Importantly, increased level of RCC2 was significantly associated with T status of tumor (P = 0.002), lymph node metastasis (P = 0.004), and advanced clinical stage (P = 0.001). Patients with LUAD with higher expression of RCC2 had shorter overall survival. Cox regression analysis demonstrated that RCC2 was an independent poorer prognostic factor for patients with LUAD. Moreover, forced expression of RCC2 promoted intrapulmonary metastasis in vivo and significantly enhanced LUAD cell migration, invasion, and proliferation in vitro. Further study found that RCC2 induced epithelial–mesenchymal transition (EMT) and also stimulated the expression of MMP-2 and MMP-9. In addition, RCC2 was able to activate JNK, while inhibition of JNK suppressed the effect of RCC2 on LUAD cell migration, invasion, EMT, and the expression of MMP-2 and MMP-9.Conclusions: RCC2 plays a pivotal role in LUAD metastasis by inducing EMT via activation of MAPK–JNK signaling. Clin Cancer Res; 23(18); 5598–610. ©2017 AACR.

Intestinal intraepithelial lymphocytes (IELs) are distributed along the length of the intestine and are considered the frontline of immune surveillance. The precise molecular mechanisms, especially epigenetic regulation, of their development and function are poorly understood. The trimethylation of histone 3 at lysine 27 (H3K27Me3) is a kind of histone modifications and associated with gene repression. Kdm6b is an epigenetic enzyme responsible for the demethylation of H3K27Me3 and thus promotes gene expression. Here we identified Kdm6b as an important intracellular regulator of small intestinal IELs. Mice genetically deficient for Kdm6b showed greatly reduced numbers of TCRαβ+CD8αα+ IELs. In the absence of Kdm6b, TCRαβ+CD8αα+ IELs exhibited increased apoptosis, disturbed maturation and a compromised capability to lyse target cells. Both IL-15 and Kdm6b-mediated demethylation of histone 3 at lysine 27 are responsible for the maturation of TCRαβ+CD8αα+ IELs through upregulating the expression of Gzmb and Fasl. In addition, Kdm6b also regulates the expression of the gut-homing molecule CCR9 by controlling H3K27Me3 level at its promoter. However, Kdm6b is dispensable for the reactivity of thymic precursors of TCRαβ+CD8αα+ IELs (IELPs) to IL-15 and TGF-β. In conclusion, we showed that Kdm6b plays critical roles in the maturation and cytotoxic function of small intestinal TCRαβ+CD8αα+ IELs.

Chronic inflammation promotes the tumorigenesis and cell stemness maintenance of colorectal cancer (CRC). However, the bridge role of long noncoding RNA (lncRNA) in linking chronic inflammation to CRC development and progression needs better understanding. Here, we elucidated a novel function of lncRNA GMDS-AS1 in persistently activated signal transducer and transcription activator 3 (STAT3) and Wnt signaling and CRC tumorigenesis. Interleukin-6 (IL-6) and Wnt3a induced lncRNA GMDS-AS1 expression, which was highly expressed in the CRC tissues and plasma of CRC patients. GMDS-AS1 knockdown impaired the survival, proliferation and stem cell-like phenotype acquisition of CRC cells in vitro and in vivo. We performed RNA sequencing (RNA-seq) and mass spectrometry (MS) to probe target proteins and identify their contributions to the downstream signaling pathways of GMDS-AS1. In CRC cells, GMDS-AS1 physically interacted with the RNA-stabilizing protein HuR, thereby protecting the HuR protein from polyubiquitination- and proteasome-dependent degradation. HuR stabilized STAT3 mRNA and upregulated the levels of basal and phosphorylated STAT3 protein, persistently activating STAT3 signaling. Our research revealed that the lncRNA GMDS-AS1 and its direct target HuR constitutively activate STAT3/Wnt signaling and promote CRC tumorigenesis, the GMDS-AS1-HuR-STAT3/Wnt axis is a therapeutic, diagnostic and prognostic target in CRC.

Purpose. We examined whether anlotinib can attenuate folic acid-induced and unilateral ureteral obstruction-induced renal fibrosis and explored the underlying antifibrotic mechanism. Materials and Methods. We have evaluated the effects of anlotinib on folic acid-induced and unilateral ureteral obstruction-induced renal fibrosis in mice through in vivo experiments of unilateral ureteral obstruction or folic acid-induced interstitial fibrosis and in vitro models of transforming growth factor-β1 induced HK-2 human renal proximal tubule cells. Serum renal function parameters and inflammatory cytokine levels were measured, and histological changes of renal injury and fibrosis were analyzed by HE staining and immunohistochemistry. Immunohistochemistry and Western blotting were used to determine the mechanism of action of anlotinib in ameliorating renal fibrosis. Results. Anlotinib improved proteinuria and reduced renal impairment in folic acid-induced mouse models of renal fibrosis. Anlotinib reduced tubular injury, deposition of tubular extracellular matrix, and expression of alpha-smooth muscle actin, transforming growth factor-β1, and cytosolic inflammatory factors compared with controls. Conclusions. Anlotinib ameliorated renal function, improved extracellular matrix deposition, reduced protein levels of epithelial-mesenchymal transition markers, and decreased cellular inflammatory factors. Anlotinib reduced renal injury and fibrosis by inhibiting the transforming growth factor-β1 signaling pathway through AKT and ERK channels.

PurposeThis study aimed to identify independent prognosis-associated factors of bone-metastatic prostate cancer. The nomograms were further developed to obtain indicators for the prognostic evaluation.MethodsA total of 7315 bone-metastatic prostate cancer (PCa) patients from 2010 to 2016 were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training cohort (n=5,120) and test cohort (n=2,195) in a ratio of 7:3. Univariate and multivariate Cox regression models were applied to evaluate potential risk factors. A 1:1 propensity score matching (PSM) was further performed to decrease the confounding effect and re-evaluate the influence of radical prostatectomy and chemotherapy on prognosis. Combining these potential prognosis factors, the nomograms of cancer-specific survival (CSS) and overall survival (OS) at different times were established. C-indexes, calibration curves, and decision curves were developed to evaluate the discrimination, calibration, and clinical benefit of the nomograms.ResultsEleven independent prognosis factors for CSS and twelve for OS were utilized to conduct the nomograms respectively. The C-indexes of nomograms for CSS and OS were 0.712 and 0.702, respectively. A favorable consistency between the predicted and actual survival probabilities was demonstrated by adopting calibration curves. Decision curves also exhibited a positive clinical benefit of the nomograms.ConclusionsNomograms were formulated successfully to predict 3-year and 5-year CSS and OS for bone-metastatic PCa patients. Radical prostatectomy and chemotherapy were strongly associated with the bone-metastatic PCa prognosis.

Aggressiveness and drug resistant are major challenges in the clinical treatment of glioblastoma (GBM). Our previously research reported a novel candidate oncogene ribosomal protein L22 like 1 (RPL22L1). The aim of this study was to elucidate the potential role and mechanism of RPL22L1 in progression and temozolomide (TMZ) resistance of GBM. Online database, tissue microarrays and clinical tissue specimens were used to evaluate the expression and clinical implication of RPL22L1 in GBM. We performed cell function assays, orthotopic and subcutaneous xenograft tumor models to evaluate the effects and molecular mechanisms of RPL22L1 on GBM. RPL22L1 expression was significantly upregulated in GBM and associated with poorer prognosis. RPL22L1 overexpression enhanced GBM cell proliferation, migration, invasion, TMZ resistance and tumorigenicity, which could be reduced by RPL22L1 knockdown. Further, we found RPL22L1 promoted mesenchymal phenotype of GBM and the impact of these effects was closely related to EGFR/STAT3 pathway. Importantly, we observed that STAT3 specific inhibitor (Stattic) significantly inhibited the malignant functions of RPL22L1, especially on TMZ resistance. RPL22L1 overexpressed increased combination drug sensitive of Stattic and TMZ both in vitro and in vivo. Moreover, Stattic effectively restored the sensitive of RPL22L1 induced TMZ-resistant in vitro and in vivo. Our study identified a novel candidate oncogene RPL22L1 which promoted the GBM malignancy through STAT3 pathway. And we highlighted that Stattic combined with TMZ therapy might be an effective treatment strategy in RPL22L1 high-expressed GBM patients.

AimThe aim of this study is to investigate the advantages and disadvantages of regional and intermittent hepatic inflow occlusion in laparoscopic hepatectomy.MethodsThe clinical data of 180 patients who underwent laparoscopic liver surgery in Taizhou People’s Hospital from 2015 to 2021 were analyzed retrospectively. The patients were divided into the regional occlusion group (n = 74) and the Pringle’s maneuver occlusion group (n = 106) according to the technique used in the intraoperative hepatic inflow occlusion. The pre- and intra-operative indicators, postoperative recovery indicators, and complications of the two groups were compared.ResultsThere were no significant differences (p > 0.05) between the groups in terms of sex, age, preoperative alanine aminotransferase (ALT), preoperative aspartate aminotransferase (AST), preoperative albumin, alpha-fetoprotein, liver cirrhosis, hepatitis B, tumor location, gas embolism, intraoperative blood transfusion, postoperative albumin, postoperative total bilirubin (TBIL), postoperative hospital stays, and complications. The preoperative TBIL and operation time were higher in the regional occlusion group than in the Pringle’s maneuver occlusion group, while the amount of intraoperative bleeding, postoperative ALT, and AST in the regional occlusion group were significantly lower than those in the Pringle’s maneuver occlusion group (p < 0.05).ConclusionThe two occlusion techniques are equally safe and effective, but regional hepatic inflow occlusion is more advantageous in operation continuity, intraoperative bleeding, and postoperative liver function recovery. The long duration and high precision of the regional blood flow occlusion technique demands a more experienced physician with a higher level of operation; therefore, it can be performed by experienced laparoscopic liver surgeons.

Objective: This retrospective study aimed to present our surgical experience in patients with primary retroperitoneal tumors (PRTs) who underwent laparoscopic surgery and to compare the results wit...

Papillary thyroid carcinoma (PTC), a common malignancy, poses a threat to human health. It has been identified that tRNA-derived fragments (tRFs) can be new putative biomarkers and targets for cancer treatment. The object of this research was to investigate the biological role and mechanism of main tRF-18-H7PU4HD2 (tRF-18) in PTC. The biological effects of tRF-18 on PTC cell proliferation and apoptosis were explored by Cell Counting Kit-8 assays, colony formation assays, and flow cytometry analysis. Additionally, Western blot analysis was performed to quantify protein levels of apoptotic markers in PTC cells. Moreover, xenograft model in nude mice was established to investigate the impact of tRF-18 on tumor growth in vivo. The interaction between tRF-18 and messenger RNA kinesin family member 1B (KIF1B) was validated via RNA immunoprecipitation assays and luciferase reporter assays. tRF-18 exhibited high expression in PTC tissues. Further, the upregulation of tRF-18 was also detected in TPC-1 and IHH4 cell lines. Importantly, tRF-18 inhibition restrained PTC cell proliferation and promoted cell apoptosis. In addition, tRF-18 inhibition suppressed xenograft tumor growth. Mechanistically, tRF-18 was confirmed to target KIF1B and negatively regulate KIF1B expression in PTC cells. tRF-18 facilitates PTC cell proliferation and inhibits cell apoptosis by targeting KIF1B.

Precision medicine in hepatocellular carcinoma (HCC) relies on validated biomarkers that help subgroup patients for targeted treatment. Here, we identified a novel candidate oncogene, ribosomal protein L22-like1 (RPL22L1), which was markedly elevated in HCC, contributed to HCC malignancy and adverse patient survival. Functional studies indicated RPL22L1 overexpression accelerated cell proliferation, migration, invasion and sorafenib resistance. Mechanism studies revealed that RPL22L1 activated ERK to induce atypical epithelial-to-mesenchymal transition (EMT) progress. Importantly, the ERK inhibitor (ERKi) could potentiate sorafenib efficiency in RPL22L1-high HCC cells. In summary, these data uncover RPL22L1 is a potential marker to guide precision therapy for utilizing ERKi to enhance the sorafenib efficacy in RPL22L1-high HCC patients.

BackgroundThe coronavirus disease (COVID-19) pandemic has posed a significant challenge for global health systems. Increasing evidence shows that asthma phenotypes and comorbidities are major risk factors for COVID-19 symptom severity. However, the molecular mechanisms underlying the association between COVID-19 and asthma are poorly understood. Therefore, we conducted bioinformatics and systems biology analysis to identify common pathways and molecular biomarkers in patients with COVID-19 and asthma, as well as potential molecular mechanisms and candidate drugs for treating patients with both COVID-19 and asthma.MethodsTwo sets of differentially expressed genes (DEGs) from the GSE171110 and GSE143192 datasets were intersected to identify common hub genes, shared pathways, and candidate drugs. In addition, murine models were utilized to explore the expression levels and associations of the hub genes in asthma and lung inflammation/injury.ResultsWe discovered 157 common DEGs between the asthma and COVID-19 datasets. A protein–protein-interaction network was built using various combinatorial statistical approaches and bioinformatics tools, which revealed several hub genes and critical modules. Six of the hub genes were markedly elevated in murine asthmatic lungs and were positively associated with IL-5, IL-13 and MUC5AC, which are the key mediators of allergic asthma. Gene Ontology and pathway analysis revealed common associations between asthma and COVID-19 progression. Finally, we identified transcription factor–gene interactions, DEG–microRNA coregulatory networks, and potential drug and chemical-compound interactions using the hub genes.ConclusionWe identified the top 15 hub genes that can be used as novel biomarkers of COVID-19 and asthma and discovered several promising candidate drugs that might be helpful for treating patients with COVID-19 and asthma.

Recent evidence suggests the global incidence and mortality of hepatocellular carcinoma (HCC) are increasing. Although the highest incidence of HCC remains entrenched in WHO regions with high levels of HBV-HCV infection, the etiology of this disease is rapidly changing to include other lifestyle risk factors. Extrahepatic metastasis is a frequent feature of advanced HCC and most commonly locates in the lungs and bone. Bone metastasis in HCC (HCC-BM) signals a more aggressive stage of disease and a poorer prognosis, simultaneously HCC-BM compromises the function and integrity of bone tissue. HCC induced osteolysis is a prominent feature of metastasis that complicates treatment needed for pathologic fractures, bone pain and other skeletal events like hypercalcemia and nerve compression. Early detection of bone metastases facilitates the treatment strategy for avoiding and relieving complications. Although recent therapeutic advances in HCC like targeting agents and immunotherapy have improved survival, the prognosis for patients with HCC-BM remains problematic. The identification of critical HCC-BM pathways in the bone microenvironment could provide important insights to guide future detection and therapy. This review presents an overview of the clinical development of bone metastases in HCC, identifying key clinical features and identifying potential molecular targets that can be deployed as diagnostic tools or therapeutic agents.

Pancreaticoduodenectomy (PD) is one of the most complex and delicate operations in abdominal surgery. With the development of laparoscopic techniques, more and more pancreatic experts have become skilled in laparoscopic pancreaticoduodenectomy (LPD). However, the short-term efficacy of LPD compared to open pancreaticoduodenectomy (OPD) remains unclear. Here, we performed a propensity score matching study aiming to compare the short outcomes of patients who underwent LPD or OPD after the learning curve and established a risk model of pancreatic fistula. The data of 346 patients who had OPD or LPD from July 2015 to January 2020 were retrieved. After a 1:1 matching, 224 patients remained. The operation time was significantly longer (P = 0.001) but the amount of bleeding was significantly lower (P = 0.001) in the LPD group than in the OPD group. Patients in LPD group had fewer blood transfusions (P = 0.002) than those in OPD group. More lymph nodes (P

Primary hepatocellular carcinoma (PHC) is one of the most common malignancies in clinical practice. According to the “Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China,” PHC, at an early stage, can be treated by surgical resection and ablation. Surgical resection basically consists of two ways; one is open hepatectomy (OH), and the other is laparoscopic hepatectomy (LH), which is a newly developed technique associated with advantages of open surgery. Ablation, also known as percutaneous thermal ablation using radiofrequency ablation (RFA) and microwave ablation (MWA), is a minimally invasive curative treatment for hepatocellular carcinoma. This preliminary report was aimed at evaluating the postoperative outcome of the patients undergoing these three therapeutic methods, respectively. The study analyzed the data of 95 patients who underwent LH, OH, or ablation between June 2018 and June 2019 at First People’s Hospital of Changzhou, Third Affiliated Hospital of Soochow University. There were 20 patients in the ablation group, 35 patients in the OH group, and 40 patients in the LH group. Among the three groups, the postoperative short-term outcome was the best in the ablation group, suggesting that it was a safe and cheap way to treat PHC at an early stage.

Background: To compare the endoscopic thyroidectomy (ET) with the open thyroidectomy (OT) for patients with papillary thyroid carcinomas and share our experience of central lymph nodes dissection a...

The purpose of the study is to evaluate whether laparoscopic pancreatoduodenectomy (LPD) is safe and feasible for elderly patients. From December 2015 to January 2019, 142 LPD surgeries and 93 OPD surgeries were performed by the same surgeon in the third affiliated hospital of Soochow University. After applying the inclusion and exclusion criteria, we retrospectively collected the date of three defined groups: LPD aged

Objective. To forecast the onset of microvascular invasion (MVI) in patients with hepatoma by evaluating the preoperative aspartate aminotransferase-to-platelet ratio index (APRI), alpha-fetoprotein (AFP), neutrophil-to-lymphocyte ratio (NLR), and other clinicopathological data. Methods. In this study, we retrospectively analysed the clinical data of 62 patients who received radical surgery for hepa toma from 2019 to 2021. Patients were separated into the MVI-negative group and the MVI-positive group according to the postoperative pathological diagnosis. The relationships between MVI and NLR, APRI, AFP, tumor size, and other clinical data were assessed using the univariate analysis, receiver operating characteristic (ROC) curve, least absolute shrinkage and selection operator (LASSO) analysis, and logistic analysis. Results. The ROC curve determined that the cutoff values of NLR, platelet-to-lymphocyte ratio (PLR), and APRI were 1.520, 98, and 0.275, respectively. The univariate analysis showed that the MVI-positive result was associated with five factors: tumor size ( χ 2 = 10.620 , p = 0.001 ), AFP ( χ 2 = 10.524 , p = 0.001 ), Edmondson grade ( χ 2 = 20.736 , p < 0.001 ), NLR ( χ 2 = 8.744 , p = 0.003 ), and APRI ( χ 2 = 4.849 , p = 0.028 ). The LASSO analysis indicated that the risk factors were the number of tumors, PLR, APRI, NLR, AFP, Edmondson grade, and tumor size. The multivariate logistic regression analysis showed that NLR ≥ 1.520 (OR 11.119, p = 0.006 ), APRI ≥ 0.275 (OR 12.515, p = 0.009 ), AFP ≥ 200 μg/mL (OR 7.823, p = 0.016 ), and tumor size > 3 cm (OR 7.689, p = 0.022 ) were independent risk factors for MVI in patients with hepatoma. Conclusion. Preoperative NLR, APRI, AFP, and tumor size are reliable indicators for predicting the appearance of MVI in patients with hepatoma and are of great value in making detailed and reliable treatment protocols for these patients before surgery.

N6-methyladenosine (m6A) RNA modification is a reversible mechanism that regulates eukaryotic gene expression. Growing evidence has demonstrated an association between m6A modification and tumorigenesis and response to immunotherapy. However, the overall influence of m6A regulators on the tumor microenvironment and their effect on the response to immunotherapy in lung adenocarcinoma remains to be explored. Here, we comprehensively analyzed the m6A modification patterns of 936 lung adenocarcinoma samples based on 24 m6A regulators. First, we described the features of genetic variation in these m6A regulators. Many m6A regulators were aberrantly expressed in tumors and negatively correlated with most tumor-infiltrating immune cell types. Furthermore, we identified three m6A modification patterns using a consensus clustering method. m6A cluster B was preferentially associated with a favorable prognosis and enriched in metabolism-associated pathways. In contrast, m6A cluster A was associated with the worst prognosis and was enriched in the process of DNA repair. m6A cluster C was characterized by activation of the immune system and a higher stromal cell score. Surprisingly, patients who received radiotherapy had a better prognosis than patients without radiotherapy only in the m6A cluster C group. Subsequently, we constructed an m6A score model that qualified the m6A modification level of individual samples by using principal component analysis algorithms. Patients with high m6A score were characterized by enhanced immune cell infiltration and prolonged survival time and were associated with lower tumor mutation burden and PD-1/CTLA4 expression. The combination of the m6A score and tumor mutation burden could accurately predict the prognosis of patients with lung adenocarcinoma. Furthermore, patients with high m6A score exhibited greater prognostic benefits from radiotherapy and immunotherapy. This study demonstrates that m6A modification is significantly associated with tumor microenvironment diversity and prognosis. A comprehensive evaluation of m6A modification patterns in single tumors will expand our understanding of the tumor immune landscape. In addition, our m6A score model demonstrated that the level of immune cell infiltration plays a significant role in cancer immunotherapy and provides a basis to increase the efficiency of current immune therapies and promote the clinical success of immunotherapy.

BACKGROUND: The identification of disease-related biological modules plays an important role in our understanding of the process of diseases. Although single-cell RNA sequencing (scRNA-seq) provides high-resolution transcriptome data that can potentially characterize subtle gene expression changes within cells, the susceptibility of the gene expression information to the influence of individual genes also makes it difficult to distinguish the biological module. METHODS: To quantify gene expression information for biological function modules, we adopted the method based on Shannon’s entropy and Spearman rank correlation analysis. The ingenious combination of these two methods enables the variation analysis of the former and the consistency analysis of the latter to make a more robust biological function analysis tool. RESULTS: We developed a computational analytical method and desktop application called NonLoss to analyze scRNA-seq data more robustly and to extract real biological differences between cell populations. The method derives its power by handling expression level data from all genes annotated to a specific function module, both for dimensionality reduction and reliability of function identification, avoiding random disturbance of individual genes. NonLoss can in principle be used to assess changes of function modules and identify vital functions simultaneously. Furthermore, specific genes contributing to important functions, even those with subtle expression changes, can be identified. The results demonstrated that NonLoss yields biologically significant insights into 3 different applications. CONCLUSIONS: NonLoss was developed with a user-friendly graphical user interface, and it could identify the module of biologically relevant expression changes at a single-cell resolution.

This study aimed to determine long non‐coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) expression in pancreatic cancer and to explore the potential molecular actions of SNHG14 in mediating pancreatic cancer progression. Gene expression was detected by quantitative real‐time PCR. Cell proliferation, growth and invasion were detected by respective CCK‐8, colony formation, and transwell invasion assays. Protein levels were measured by Western blotting. Cell apoptosis and caspase‐3 activity were detected by flow cytometry and caspase‐3 activity assay. The link between miR‐613 and its targets was evaluated by luciferase reporter assay. In vivo tumour growth was evaluated using a xenograft model of nude mice. SNHG14 expression was up‐regulated in cancerous tissues from pancreatic cancer patients. High expression of SNHG14 was associated with poor tumour differentiation, advanced TNM stage and nodal metastasis. SNHG14 overexpression enhanced cell proliferative, growth and invasive abilities, and suppressed apoptotic rates and caspase‐3 activity in pancreatic cancer cells, while SNHG14 knockdown exerted opposite effects. Mechanistic studies revealed that miR‐613 was targeted by SNHG14, and Annexin A2 (ANXA2) was targeted and inversely regulated by miR‐613 in pancreatic cancer cells. In vivo studies showed that SNHG14 knockdown attenuated tumour growth. MiR‐613 was down‐regulated and ANXA2 was up‐regulated in the pancreatic cancer tissues, and SNHG14 expression levels were inversely correlated with miR‐613 expression levels and positively correlated with the ANXA2 mRNA expression levels. Collectively, our results suggest that SNHG14 potentiates pancreatic cancer progression through modulation of annexin A2 expression via acting as a competing endogenous RNA for miR‐613.

Introduction and Objectives The fibrosis score 4 (FIB-4) has been identified as a biochemical surrogate for histological fibrogenesis and fibrosis in cirrhosis. This study investigates the impact of preoperative FIB-4 on postoperative liver failure of patients with hepatocellular carcinoma (HCC). Materials and methods Data from 205 patients who underwent curative resection for HCC were retrospectively analyzed. The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the FIB-4. Univariate analysis and multivariate analysis were performed to identify risk factors for postoperative liver failure. The clinical outcomes were compared between patients with high FIB-4 and low FIB-4. Results The optimal cutoff value of the FIB-4 was set at 5.92 for postoperative liver failure according to ROC curve. By univariate and multivariate analysis, the number of resected segments, FIB-4, and model for end-stage liver disease score were identified as independent risk factors for postoperative liver failure. Patients with preoperative FIB-4 > 5.92 had poorer liver function and higher occurrence of postoperative liver failure. Conclusions Preoperative FIB-4 was associated with postoperative liver failure. Patients with preoperative FIB-4 > 5.92 carry a high risk of postoperative liver failure.

Central lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is common. But the association between primary tumor characteristics and specific features of metastatic lymph nodes in PTC has not been fully identified. Determining risk factors for LNM may help surgeons determine rational extent of lymph node dissection. Data from 432 patients who underwent thyroidectomy with cervical lymph node dissection for PTC were retrospectively analyzed. The relationships between LNM to central compartment or lateral compartment and clinicopathologic factors were analyzed. Cox regression model was used to determine the risk factors for recurrence-free survival (RFS). Central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) were found in 216 (50.0%) and 65 (15.0%) patients, respectively. In the multivariate analysis for CLNM, patients

Ischemia-reperfusion injury (IRI) of the liver is a severe complication that can follow hemorrhagic shock and liver surgery. Regulatory T cells (Treg) show the potential of improving outcomes of IRI. Everolimus is an mTOR inhibitor used in liver transplantation and the treatment of tumor patients through PI3K/AKT/mTOR pathway. The present study was designed to investigate the efficacy and mechanism of everolimus on Treg for the treatment of IRI. Hepatocytes were exposed to H

In recent years, environmental protection technology has developed by leaps and bounds. The weather pollution monitoring tool is a new type of product that can conduct real-time continuous weather surveys, pollution monitoring, and pollution source location under various terrain conditions. It can not only be used as an ordinary Xiaoma weather station, but also can be used to detect pollution levels close to the ground. In terms of meteorological data collection, with meteorological sensors as the core, environmental information can be converted into electrical signals. Finally, the meteorological information is obtained through the hardware circuit. This article introduces a new detection tool based on the Internet. In the mechanical structure, crawler-type movement and double-layer shock absorption structure are adopted to ensure the stability of motion in complex terrain and realize the function of autonomous heading reversal.

Due to high energy and material metabolism requirements, mitochondria are frequently active in tumor cells. Our study found that the high energy metabolism status is positively correlated with the poor prognosis of patients with lung adenocarcinoma. We constructed a scoring system (mitoRiskscore) based on the gene expression of specific mitochondrial localized proteins through univariate and LASSO cox regression. It has been shown that high mitoRiskscore was correlated with a shorter survival time after surgery in patients with lung adenocarcinoma. Compared with the typical TNM grading system, the mitoRiskscore gene panel had higher prediction accuracy. A vast number of external verification results ensured its universality. Additionally, the mitoRiskscore could evaluate the metabolic pattern and chemotherapy sensitivity of the tumor samples. Lung adenocarcinoma with higher mitoRiskscore was more active in glycolysis, and oxidative phosphorylation expression of proliferation-related pathway genes was also significantly upregulated. In contrast, patients with low mitoRiskscore had similar metabolic patterns to normal tissues. In order to improve the accuracy of prediction ability and promote clinical usage, we developed a nomogram that combined mitoRiskscore and clinical prognostic factors to predict the 3-year, 5-year, and 10-year survival rates of patients. We also performed in vitro experiments to verify the function of the key genes in the mitoRiskscore panel. In conclusion, the mitoRiskscore scoring system may assist clinicians to judge the postoperative survival rate and chemotherapy of patients with lung adenocarcinoma.

Background. Hepatoma is a leading cause of death worldwide, with high metastasis and recurrence rates. The aberrant expression of miRNA-130a-5p is involved in the development and progression of various cancers. However, there are no studies investigating the role of miRNA-130a-5p in hepatoma. The present study is aimed at clarifying the functional role of miRNA-130a-5p in hepatoma progression. Methods. The expression levels of miRNA-130a-5p in hepatoma tissues and cell lines were detected by qRT-PCR assays. Bioinformatic analysis, gain-/loss-of-function experiments, and luciferase activity assays were conducted to verify whether miRNA-130a-5p is targeted by protein tyrosine phosphatase 4A2 (PTP4A2). The functions of miRNA-130a-5p and PTP4A2 in hepatoma were determined by cell proliferation assays. Results. The expression of miRNA-130a-5p was downregulated in hepatoma tissues and was related to poor prognosis. However, the expression level of PTP4A2 was contradictory to that of miRNA-130a-5p, and PTP4A2 upregulation could aggravate hepatoma progression. The ectopic overexpression of PTP4A2 promoted hepatoma cell proliferation in vitro, which could be reversed by miRNA-130a-5p. Conclusions. Our study implies that miRNA-130a-5p, which is downregulated in hepatoma tissues, can suppress hepatoma cell proliferation via targeting PTP4A2.

Pancreaticoduodenectomy (PD) is one of the most complex and delicate operations in abdominal surgery. With the development of laparoscopic techniques, more and more pancreatic experts have become skilled in laparoscopic pancreaticoduodenectomy (LPD). However, the short-term efficacy of LPD compared to open pancreaticoduodenectomy (OPD) remains unclear. Here, we performed a propensity score matching study aiming to compare the short outcomes of patients who underwent LPD or OPD after the learning curve and established a risk model of pancreatic fistula. The data of 346 patients who had OPD or LPD from July 2015 to January 2020 were retrieved. After a 1:1 matching, 224 patients remained. The operation time was significantly longer (P = 0.001) but the amount of bleeding was significantly lower (P = 0.001) in the LPD group than in the OPD group. Patients in LPD group had fewer blood transfusions (P = 0.002) than those in OPD group. More lymph nodes (P 0.001) were dissected in LPD group. The rate of grade B/C pancreatic fistula was significantly higher in the LPD group than in the OPD group (16.1% vs. 6.3%, P = 0.002). By multi variate Logistic regression analysis, we identified pancreatic tumor, malignancy and low body mass index were risk factors of Grade B/C pancreatic fistula after PD operation. Then, we developed a Grade B/C pancreatic fistula nomogram with the risk factors. The C-index of the nomogram was 0.836 (95% CI 0.762-0.910). In conclusion, LPD could be technically feasible, get less trauma and achieve similar short-term outcome as compared with OPD.

A number of inflammation indicators based on C-reactive protein (CRP) and albumin have been widely used to predict the prognosis in several types of tumors, but their functions in gallbladder cancer (GBC) have rarely been explored. The aim of our study is to evaluate and compare the prognostic values of the C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS) and high-sensitivity modified Glasgow prognostic score (HS-mGPS) in patients with GBC. 144 GBC patients who received curative surgery in our hospital from January 2010 to May 2017 were enrolled in this research. The Kaplan-Meier analysis showed that the median OS of the patients in the high CAR group was significantly shorter than the patients in the low group (p < 0.001), and higher scores of GPS, mGPS and HS-mGPS were also associated with decreased OS, respectively. However, according to the Receiver Operating Characteristic (ROC) curve, the CAR was superior to the other prognostic scores in determining the prognosis for the GBC patients. In the multivariate analysis, CAR was verified as an independent risk factor for poor prognosis, together with tumor differentiation, T stage and postoperative complications. All in all, compared to the other three CRP-albumin-related prognostic predictors, CRA is a better indicator in predicting poor long-term outcomes in GBC patients after radical surgery.

Background: To explore the clinical efficacy and long-term prognosis of laparoscopic technique in patients with gallbladder cancer.Methods: Retrospective analysis and summary of the clinical data of 50 patients with gallbladder carcinoma treated by laparoscope from January 2010 to November 2018 in the Third Affiliated Hospital of Soochow University.Results: The intraoperative or postoperative pathology of 43 cases were confirmed as the gallbladder carcinoma. Among them, 11 cases were confirmed as Tis stage, 12 cases as T1b stage, 20 cases as T2 stage and 7 cases as T3 stage. Follow up data of one patient was lost due to personal reason. During the follow-up period, no one at Tis stage died, two cases at T1b stage died, six cases at T2 stage died and six cases at T3 stage died. Conclusion: Laparoscope is a secure and feasible way in the treatment of gallbladder carcinoma at an early stage, but a large number of clinical data is still required to demonstrate its long-term curative effect.

Objective To analyse potential risk factors for postoperative pancreatic fistula (POPF). Methods A retrospective study on risk factors for POPF was conducted in patients undergoing laparoscopic pancreatoduodenectomy. Basic characteristics, and preoperative, intraoperative and postoperative patient data were collected and analysed. Results A total of 268 patients were enrolled in this study, including 54 patients with POPF following surgery (POPF incidence, 20.15%). Univariate analysis indicated that patient’s age, body mass index (BMI), preoperative bilirubin level, pancreas texture, and drainage fluid amylase level on day 1 following surgery were associated with POPF. Multiple logistic regression analysis indicated that preoperative bilirubin level ≥170 µmol/l, soft pancreas texture, BMI ≥25, and age ≥65 years were independent risk factors associated with POPF. Conclusions For patients with preoperative bilirubin level ≥170 µmol/l, soft pancreas texture, BMI ≥25 and age ≥65 years, clinically relevant measures should be taken as early as possible for the prophylaxis of POPF.

Background Surgery is a potential cure for hepatocellular carcinoma (HCC), but its postoperative recurrence rate is high, its prognosis is poor, and reliable predictive indicators are lacking. This study was conducted to develop a simple, practical, and effective predictive model. Materials and methods Preoperative clinical and postoperative pathological data on patients with HCC undergoing partial hepatectomies at the Third Affiliated Hospital of Soochow University from January 2010 to December 2015 were retrospectively analyzed, and a nomogram was constructed. The model performance was evaluated using C-indexes, receiver operating characteristic curves, and calibration curves. The results were verified from validation cohort data collected at the same center from January 2016 to January 2017 and compared with the traditional staging systems. Results Three hundred three patients were enrolled in this study: 238 in the training cohort and 65 in the validation cohort. From the univariate and multivariate Cox regression analyses in the training cohort, six independent risk factors, i.e., age, alpha-fetoprotein (AFP), tumor size, satellite nodules, systemic immune inflammation index (SII), and prognostic nutritional index (PNI), were filtered and included in the nomogram. The C-index was 0.701 [95% confidence interval (CI): 0.654-0.748] in the training cohort and 0.705 (95% CI: 0.619-0.791) in the validation cohort. The areas under the curve for the 1- and 3-year recurrence-free survival were 0.706 and 0.716 in the training cohort and 0.686 and 0.743 in the validation cohort, respectively. The calibration curves showed good agreement. Compared with traditional American Joint Committee on Cancer 8th edition (AJCC8th) and Barcelona Clinic Liver Cancer (BCLC) staging systems, our nomogram showed better predictive ability. Conclusion Our nomogram is simple, practical, and reliable. According to our nomogram, predicting the risk of recurrence and stratifying HCC patient management will yield the greatest survival benefit for patients.

Drug resistance of Taxol leads to the treatment failure in hepatocellular carcinoma (HCC). LncRNA HOTAIR have drawn increasing attention in various diseases; its function and mechanism in Taxol-resistance in HCC remain unclear. In the present study, the two Taxol resistant HCC cell lines (HepG2/Taxol and SMMC7721/Taxol) were induced. The qRT-PCR data exhibited that over-expressed HOTAIR as well as low-expressed miR-34a were founded in HepG2/Taxol and SMMC7721/Taxol cells. HOTAIR knockdown suppresses proliferation, invasion and promotes apoptosis of in HepG2/Taxol and SMMC7721/Taxol cells through up-regulating miR-34a by MTT assay, transwell invasion assays and flow cytometry, while down-regulation of miR-34a had an opposite effect on reversing Taxol resistance. Cleaved caspase-3 and Bax were significantly up-regulated by si-HOTAIR transfection, while Bcl-2 level exhibited opposite trend. Besides, HOTAIR knockdown impaired Taxol-resistance in HCC by accommodating Akt phosphorylation and Wnt/β-catenin signaling via interacting with miR-34a. The present study may afford a valuable target for treating Taxol-resistance in HCC.

Background Expression of C-C chemokine receptor type 7 (CCR7) is associated with the prognosis of several cancers. The aim of this study was to conduct the meta-analysis to determine the prognostic value of CCR7 expression in solid tumors. Materials and methods We searched for relevant literature in the PubMed, Embase, and Cochrane Library databases (last updated on January 15, 2018). The associations of CCR7 expression with overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), progress-free survival (PFS), and disease-specific survival (DSS) were estimated. Results In total, 30 qualified studies including 3,413 patients were enrolled. The results revealed that higher expression of CCR7 predicted poorer OS (pooled HR =1.79; 95% CI =1.49-2.16; P

Background/Aims: We aimed to study the involvement of circZMYM2 (hsa_circ_0099999) in pancreatic cancer (PC) cell proliferation, apoptosis and invasion and to figured out the underlying mechanism of circZMYM2 regulating miR-335-5p and JMJD2C. Methods: CircRNA differential expressions in twenty PC samples and paired normal tissue samples were analyzed using Arraystar Human CircRNA microarray V1. CircZMYM2 expression level was determined via qRT-PCR. The effects of circZMYM2 inhibition and overexpression on cell proliferation, cell apoptosis and cell invasion were investigated by CCK-8 assays, Flow cytometry assays and Transwell assays. An animal experiment on nude mice was put forward to test the influence of circZMYM2 knockdown on tumor growth. The relationship between circZMYM2, miR-335 and JMJD2C was verified by RNA pull down, dual-luciferase reporter assays and rescue experiment. The effect of circZMYM2 and miR-335-5p on the expression of JMJD2C protein was detected by western blot. Results: CircZMYM2 overexpression was observed in both PC tissues and cells. Knockdown of circZMYM2 inhibited proliferation, induced apoptosis, and weakened invasion ability of cancer cells. Tumor growth was restrained in vivo. CircZMYM2 repressed the expression of its target miR-335-5p. MiR-335-5p attenuated pancreatic cancer development via inhibition of JMJD2C. Conclusion: Our study demonstrated that circZMYM2 promoted PC progression. CircZMYM2 had a sponge effect on miR-335-5p and modulated the downstream oncogene JMJD2C.

To identify metabolic pathways that were perturbed in pancreatic cancer (PC), we investigated gene‐metabolite networks by integration of metabolomic and transcriptomic. In this research, we undertook the metabolomic study of 43 paired human PC samples, aiming to identify key metabolic alterations in PC. We also carried out in vitro experiments to validate that the key metabolite cytidine and its related gene ENTPD8 played an important role in PC cell proliferation. We screened out 13 metabolites differentially expressed in PC tissue (PCT) by liquid chromatography/mass spectrometry analysis on 34 metabolites, and the partial least square discrimination analysis results revealed that 9 metabolites among them were remarkably altered in PCT compared to adjacent noncancerous tissue (variable importance in projection >1, P

Purpose. Laparoscopic common bile duct exploration (LCBDE) has been widely used to remove common bile duct (CBD) stones. However, surgery is not considered as the first treatment choice for elderly patients with CBD stones because of the potential risk of postoperative complications. This study aims to evaluate the safety and efficiency of LCBDE for elderly patients. Methods. From April 2011 to October 2016, 265 consecutive patients underwent LCBDE. We performed a retrospective study and divided these patients into 2 groups. The younger group was younger than 70 years old (n = 179), and the elderly group was 70 years old or older (n = 86). We compared patient demographics, clinical characteristics, intraoperative parameters, postoperative complications, and incidence of recurrent stone between the 2 groups. Results. The elderly patients had higher preoperative morbidity of chronic diseases, such as pulmonary diseases, heart diseases, arterial hypertension, and abdominal operation history ( P < .05). There were no significant differences between the 2 groups in terms of operation time, intraoperative blood loss, conversion rate to open surgery, total cost, overall complications, and incidence of recurrent stone ( P > .05). Conclusion. LCBDE can also be carried out as a safe and effective approach to remove CBD stones in elderly patients, although they have higher risk of chronic diseases.

Few studies on the uncinate process-first approach in laparoscopic pancreaticoduodenectomy (LPD) have been reported. The aim of this study is to compare the perioperative outcomes of LPD to open pancreaticoduodenectomy (OPD) in terms of feasibility, safety, and efficacy using the uncinate process-first approach.This retrospective study included 102 patients who underwent pancreaticoduodenectomy between 2013 and 2017. Patients were divided into two groups based on the surgical approach: the laparoscopic surgery group (n = 47) and open surgery group (n = 55). The clinical characteristics and intra- and postoperative data were retrospectively analysed.LPD was performed successfully in all 47 patients. The mean operation time was significantly longer in the LPD group (410 ± 68 min) than in the OPD group (245 ± 70 min; P 0.05). LPD produced significantly less intraoperative blood loss (210 ± 46 mL vs 420 ± 50 mL, P 0.05), shorter first flatus time (1.5 d vs 4 d, P 0.05) and shorter diet start time (2 d vs 5 d, P 0.05). The total hospital stay was significantly shorter in the LPD group, with a median of 13 ± 4 days versus 18 ± 5.5 days in the OPD group (P 0.05). The postoperative complication rates of the LPD group and OPD group were 21.3% and 27.3%, respectively (P 0.05). The rate of category I-II complications and rate of category III-IV complications did not significantly differ (P 0.05). Pancreatic fistulae occurred in 6 patients (12.8%) in the LPD group and 8 patients (14.5%) in the OPD group (P = 0.67). Delayed gastric emptying occurred in 2 patients (4.26%) in the LPD group and 2 patients in the OPD group (3.63%; P = 0.79). Postpancreatectomy haemorrhage was not significantly different between the groups (2.13% vs 3.63%; P = 0.66).LPD with the uncinate process-first approach combines the benefits of laparoscopy with a low risk of postoperative complications and high rate of curative resection.

Conventionally, patients suffered from recurrent common bile duct (CBD) stone after cholecystectomy are suggested to be treated with endoscopic retrograde cholangiopancreaticography. This study was designed to explore the feasibility of laparoscopic common bile duct exploration (LCBDE) as a salvage procedure for recurrent CBD calculi after cholecystectomy. A retrospective review was conducted of data from 65 patients who underwent LCBDE for recurrent CBD calculi after cholecystectomy from January 2011 to July 2015. LCBDE was successfully carried out in 61 cases, with a successful rate of 93.8 per cent. Three cases required open conversion because of serious abdominal adhesion, and one case for intraoperative bleeding. Postoperative bile leakage occurred in two cases, and bile peritonitis developed in one case; all these three patients with complications were fully cured by conservative treatment. A postoperative retained CBD stone was found in one patient, which was extracted with endoscopic sphincterotomy. Furthermore, it was found that the mean operative time and length of postoperative hospital stay were much shorter in primary closure group (n = 49) than in T-tube drainage group (n = 12), and the hospital expense was also lower in primary closure group. We suggest that LCBDE could be a novel approach as a salvage procedure for the recurrent CBD stone after cholecystectomy, and we prefer to intraoperative primary closure of CBD if possible.

CXC chemokine receptor-2 (CXCR2) expression is associated with the prognosis of multiple cancers. We performed a meta-analysis to determine the association between the CXCR2 expression in tumor tissue and patient prognosis. We compiled related literature from PubMed, Embase, and Web of Science (last updated July 31, 2017). A total of 4012 patients with solid tumors from 21 studies were included to evaluate the association between CXCR2 and overall survival, recurrence-free survival, or disease-free survival. High CXCR2 expression was significantly associated with poor overall survival (pooled HR = 1.82; 95% CI = 1.63-2.03; P < 0.001), recurrence-free survival (pooled HR = 1.40; 95% CI = 1.21-1.62; P < 0.001), and disease-free survival (pooled HR = 1.89; 95% CI = 1.05-3.40; P = 0.033), especially in patients with digestive system neoplasms. Thus high CXCR2 expression in tumor tissue appears predictive of a poor prognosis in patients with solid tumors. Further studies will be required to determine whether CXCR2 blockade has a favorable effect on the prognosis of patients with cancer.

The prognostic role of COX-2 expression in ovarian cancer patients has been studied for years, while results remain controversial. Thus we performed a meta-analysis to evaluate the prognostic impact of COX-2 expression on survival of ovarian cancer patients. The databases PubMed, Embase and CNKI were searched. Summary hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to analyze the correlations between COX-2 expression and overall survival (OS), and disease-free survival (DFS). A total of 1,867 patients from 18 studies were enrolled in the final analysis. The results showed that patients with higher COX-2 expression had a poor OS (HR: 1.48; 95% CI: 1.19-1.85) and DFS (HR: 1.81, 95% CI: 1.28-2.55). Subgroup analysis showed that there had significant associations between COX-2 expression and survival rate in most of the subgroups. Furthermore, there were significant associations between COX-2 expression and several clinical parameters such as FIGO stage, histological type and age. These results showed the patients with higher COX-2 expression had a significantly poorer survival rate, COX-2 expression had the potential to be a prognostic marker of ovarian cancer.

// Yuhui Wang 1, * , Nan Wu 1, * , Bo Pang 1, * , Dandan Tong 2 , Donglin Sun 1 , Haiming Sun 1 , Chunyu Zhang 1 , Wenjing Sun 1 , Xiangning Meng 1 , Jing Bai 1 , Feng Chen 1 , Jingshu Geng 3 , Songbin Fu 1, 4 and Yan Jin 1, 4 1 Laboratory of Medical Genetics, Harbin Medical University, Harbin, China 2 Department of Pathology, Harbin Medical University, Harbin, China 3 Department of Pathology, Third Affiliated Clinical Hospital, Harbin Medical University, Harbin, China 4 Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, Harbin, China * These authors have contributed equally to this work Correspondence to: Yan Jin, email: jinyan@ems.hrbmu.edu.cn Songbin Fu, email: fusb@ems.hrbmu.edu.cn , fusongbin@yahoo.com Keywords: TRIB1, colorectal carcinoma, migration, invasion, MMP-2 Received: November 30, 2016 Accepted: May 01, 2017 Published: May 25, 2017 ABSTRACT Colorectal cancer (CRC) is the third most common cancer in the world and distant metastasis is the leading cause of death among CRC patients. However, the underlying mechanisms of distant metastasis remain largely unknown. Amplification of 8q24 is a common chromosomal abnormality in CRC. In the present study, a putative oncogene at 8q24, TRIB1, was characterized for its role in CRC metastasis and underlying molecular mechanisms. Higher expression of TRIB1 protein was detected in 58/83 (69.9%) of CRC tissues, compared with adjacent non-tumor tissues. Moreover, the expression of TRIB1 was significantly associated with distant metastasis ( P =0.043) and advanced staging ( P =0.008) in CRC tissues. TRIB1 overexpression was also correlated with poor prognosis in CRC patients as analyzed in PrognoScan database. In addition, elevated expression of TRIB1 promoted CRC cell motility and adhesive ability, while silencing of TRIB1 reduced those effects. Further study revealed that TRIB1-mediated migration and invasion of CRC cells required up-regulation of MMP-2 through the activation of FAK/Src and ERK pathway. Collectively, the results suggest that TRIB1 promotes CRC cell motility by activation MMP-2 via the FAK/Src and ERK pathways. It may provide a potential diagnostic and therapeutic target for CRC.

// Duo Liu 1, 2 , Nan Wu 1 , Haiming Sun 1 , Mei Dong 2 , Tianzhu Guo 3 , Peng Chi 4 , Guofu Li 5 , Donglin Sun 1 and Yan Jin 1 1 Department of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China 2 Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China 3 Department of Pharmacology, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China 4 Department of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang, China 5 Department of Neurosurvery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China Correspondence to: Yan Jin, email: jinyan@ems.hrbmu.edu.cn Donglin Sun, email: sundl@ems.hrbmu.edu.cn Keywords: diffuse large B-cell lymphoma, rituximab, pharmacogenetic, prognosis Received: October 19, 2016 Accepted: March 09, 2017 Published: April 06, 2017 ABSTRACT The impact of pharmacogenetics on predicting survival in diffuse large B-cell lymphoma (DLBCL) remains unclear. We tested 337 DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 9 single nucleotide polymorphisms from 6 genes ( CD20 , FCGR2A , NAD(P)H, ABCC2 , ABCG2 and CYP3A5 ). Patients who carried the NCF4 rs1883112 GG genotype showed significantly shorter progression-free survival (PFS) ( P = 0.023) and event-free survival (EFS) ( P 60 years old) or male patients with ABCG2 rs2231137 GG genotype had poorer PFS and EFS than A allele. Moreover, CD20 rs2070770 CC and RAC2 rs13058338 AT genotypes were independent predictors of chemotherapy-induced toxicity. Cox proportional hazards analyses demonstrated that the GG genotype of ABCG2 rs2231137 and NCF4 rs1883112 were risk factors in DLBCL patients. In conclusion, the identified polymorphisms provide guide for the identification of DLBCL patients who are likely to benefit from chemotherapy.

Background and Aim: Long noncoding RNA-plasmacytoma variant translocation 1 is identified to be highly expressed and exhibits oncogenic activity in a variety of human malignancies, including pancreatic cancer. However, little is known about the overall biological role and mechanism of plasmacytoma variant translocation 1 in pancreatic cancer so far. In this study, we investigated the effect of plasmacytoma variant translocation 1 on pancreatic cancer cell proliferation and migration as well as epithelial–mesenchymal transition. Methods: Pancreatic cancer tissue specimens and cell line were used in this study, with normal tissue and cell line acting as control. Results: It showed that plasmacytoma variant translocation 1 expression was significantly upregulated in pancreatic cancer tissues or cell line compared to normal groups. Plasmacytoma variant translocation 1 downregulation significantly inhibited zinc finger E-box-binding protein 1/Snail expression but promoted p21 expression, and it also inhibited the cell proliferation and migration. Additionally, p21 downregulation enhanced, and p21 overexpression repressed, zinc finger E-box-binding protein 1/Snail expression and cells proliferation in PANC-1 cells. However, p21 downregulation reversed the effect of plasmacytoma variant translocation 1 downregulation on zinc finger E-box-binding protein 1/Snail expression and cell proliferation and migration. Conclusion: Plasmacytoma variant translocation 1 promoted epithelial–mesenchymal transition and cell proliferation and migration through downregulating p21 in pancreatic cancer cells.