Poor Prognosis In Pancreatic Cancer Patients Research Articles

Prognostic value of perioperative serum low-density lipoprotein cholesterol level for postoperative prognosis of pancreatic cancer: a retrospective study

BackgroundAs a common malignant tumour, pancreatic cancer (PC) has the worst clinical outcome. Early evaluation of the postoperative prognosis has certain clinical value. Low-density lipoprotein cholesterol (LDL-c), which is mainly composed of cholesteryl esters, phospholipids, and proteins, plays an important role in transporting cholesterol into peripheral tissues. LDL-c has also been reported to be correlated with the occurrence and progression of malignant tumours and can predict postoperative prognosis in various tumours.AimsTo determine correlation between serum LDL-c level and clinical outcome in PC patients after surgery.MethodsData of PC patients that received surgery at our department from January 2015 to December 2021 were retrospectively analysed. Receiver operating characteristic (ROC) curves between perioperative serum LDL-c at different timepoints and survival rate at postoperative 1-year were drawn, and the optimal cut-off value was calculated. Patients were categorized into low and high LDL-c groups, and their clinical data and outcome were compared. Univariate and multivariate analyses were applied to screen out risk markers for poor prognosis of PC patients after surgery.ResultsThe area under the ROC curve of serum LDL-c at 4 weeks after surgery and prognosis was 0.669 (95% CI: 0.581–0.757), and the optimal cut-off value was 1.515 mmol/L. The median disease-free survival (DFS) rates of low and high LDL-c groups were 9 months and 16 months, respectively, and the 1-, 2- and 3-year DFS rates were 42.6%, 21.1% and 11.7% in low LDL-c group, respectively, and, 60.2%, 35.3% and 26.2% in high LDL-c group, respectively (P = 0.005). The median overall survival (OS) rates of low and high LDL-c groups were 12 months and 22 months, respectively, and the 1-, 2- and 3-year OS rates were 46.8%, 22.6% and 15.8% in low LDL-c group, respectively, and 77.9%, 46.8% and 30.4% in high LDL-c group, respectively (P = 0.004). Multivariate analysis confirmed low postoperative 4-week serum LDL-c as independent risk marker for early tumour recrudesce and poor clinical outcome in PC patients.ConclusionHigh postoperative 4-week serum LDL-c is a prognostic marker for prolonged DFS and OS time in PC patients.

Prognostic value of alkaline phosphatase and gamma-glutamyl transferase in patients with metastatic pancreatic cancer.

Background: Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. This studyevaluated the prognostic role of serum alanine phosphatase (ALP) and gamma-glutamyl-transferase (GGT) in metastatic PC patients. Materials & methods: 153 patients with metastatic PC receiving first-line treatment with nab-paclitaxel/gemcitabine were retrospectively enrolled in a multicenter study and stratified according to ALP (≤ or >260U/l) and GGT (≤ or >45.5U/l) levels. Results: Improved overall survival was recordedin patients with GGT levels ≤45.5U/l (p<0.05). In patients with liver metastasis, overall survival was significantly lower in patients with high ALP (p=0.01) and GGT (p=0.02). Conclusion: High levels of ALP and GGT were related to a poor prognosis in PC patients with liver metastasis receiving nab-paclitaxel/gemcitabine.

Exosome-derived FGD5-AS1 promotes tumor-associated macrophage M2 polarization-mediated pancreatic cancer cell proliferation and metastasis

Inflammatory molecules and exosomes are crucial for signal transduction between tumor-associated macrophages and tumor cells. IL-6, a key inflammatory molecule secreted by M2 macrophages after polarization, can mediate malignant progression of pancreatic cancer (PC). However, the functions and mechanisms of IL-6 and tumor-derived exosomes in tumor-associated macrophages and PC remain unclear. Transcriptome chip and quantitative reverse transcription PCR experiments indicated that FGD5-AS1 induced IL-6 and high FGD5-AS1 expression correlated with the poor prognosis in PC patients. RNA pulldown, mass spectrometry, and dual luciferase reporter assays were used to identify the mechanism of exosomal FGD5-AS1 in promoting PC progression and M2 macrophage polarization. FGD5-AS1 exerted cancer-promoting functions when co-cultured with M2 macrophages. PC-derived exosomal FGD5-AS1 stimulated M2 macrophage polarization by activating STAT3/NF-κB pathway. FGD5-AS1 interacts with p300, resulting in STAT3 acetylation, thus promoting nuclear localization and transcriptional activity of STAT3/NF-κB. These data indicated that PC cells generate FGD5-AS1-rich exosomes, which cause M2 macrophage polarization to promote the malignant behaviors of PC cells. Targeting exosomal FGD5-AS1 may provide a potential diagnosis and treatment strategy for PC.

Targeting CXCL5 in Pancreatic Cancer Cells Inhibits Cancer Xenograft Growth by Reducing Proliferation and Inhibiting EMT Progression.

Pancreatic cancer (PC) is the most lethal malignant tumor, with average survival period of about 10 months. C-X-C ligand 5 (CXCL5), an important chemokine for immune cell accumulation in tumor tissues, has been reported to be involved in a variety of human cancers. However, the exact role of CXCL5 in PC progression has not been well defined. The expression of CXCL5 in PC was analyzed based on online databases and clinical specimens immunohistochemical staining, and Western blotting of CXCL5 in PC cell lines and patient samples. The correlation between CXCL5 expression and prognosis in PC was explored. The role of CXCL5 in PC was investigated through in vitro and in vivo experiments. The expression of CXCL5 was significantly increased in PC tissues compared with that in pancreas tissues, and CXCL5 high expression predicts poor prognosis in PC patients. Further analyses demonstrated that overexpression of CXCL5 in PC cells was positively related to higher proliferation rate, higher migration ability, and higher EMT markers including SNAI2 and TWIST1 of tumor cells in vitro. Consistently, the knockdown of CXCL5 in PC cells harmed the proliferation rate, migration ability, and expression of EMT indexes of tumor cells in vitro. Importantly, knockdown of CXCL5 inhibited the growth of xenograft tumors in vivo. CXCL5 high expression predicts poor prognosis in PC patients. CXCL5 promotes PC cell growth and EMT process. Inhibition of CXCL5 may be a potential therapeutic approach for PC.

M6A RNA demethylase FTO promotes the growth, migration and invasion of pancreatic cancer cells through inhibiting TFPI-2

ABSTRACT Pancreatic cancer (PC) is one of the most fatal cancers with a very poor prognosis. Here, we found that N6-methyladenosine (m6A) RNA demethylase fat mass and obesity-related protein (FTO) promote the growth, migration and invasion of PC. FTO expression level is increased in human PC and is associated with poor prognosis of PC patients. Knockdown of FTO increases m6A methylation of TFPI-2 mRNA in PC cells, thereby increasing mRNA stability via the m6A reader YTHDF1, resulting in up-regulation of TFPI-2 expression, and inhibits PC proliferation, colony formation, sphere formation, migration and invasion in vitro, as well as tumour growth in vivo. Rescue assay further confirms that FTO facilitates cancer progression by reducing the expression of TFPI-2. Mechanistically, FTO promotes the progression of PC at least partially through reducing m6A/YTHDF1 mediated TFPI-2 mRNA stability. Our findings reveal that FTO, as an m6A demethylase, plays a critical role in promoting PC growth, migration and invasion, suggesting that FTO may be a potential therapeutic target for treating PC.

Roles and Clinical Significances of ATF6, EMC6, and APAF1 in Prognosis of Pancreatic Cancer.

Background: Pancreatic cancer (PC) is prevalent among malignant tumors with poor prognosis and lacks efficient therapeutic strategies. Endoplasmic reticulum (ER) stress and apoptosis are associated with chronic inflammation and cancer progression. However, the prognostic value of ER stress-related, and apoptosis-related genes in PC remains to be further elucidated. Our study aimed at confirming the prognostic values of the ER stress-related genes, ATF6, EMC6, XBP1, and CHOP, and the apoptosis-related gene, APAF1, in PC patients. Methods: Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was used to evaluate prognosis value of ATF6, EMC6, XBP1, CHOP, and APAF1 in PC. Clinical data from 69 PC patients were retrospectively analyzed. Immunohistochemistry, Western blotting, and qRT-PCR were used for the assessment of gene or protein expression. The cell counting kit-8 (CCK-8) and the Transwell invasion assays were, respectively, used for the assessment of the proliferative and invasive abilities of PC cells. The prognostic values of ATF6, XBP1, CHOP, EMC6, and APAF1 in PC patients were evaluated using Kaplan–Meier and Cox regression analyses. Results: XBP1 and CHOP expressions were not associated with PC recurrence-free survival (RFS), overall survival (OS) and disease-specific survival (DSS). ATF6 upregulation and EMC6 and APAF1 downregulations significantly correlated with the poor RFS, OS, and DSS of PC patients. ATF6 promoted PC cell proliferation and invasion, while EMC6 and APAF1 inhibited these events. Conclusion: ATF6 upregulation and EMC6 and APAF1 downregulations may be valid indicators of poor prognosis of PC patients. Moreover, ATF6, EMC6, and APAF1 may constitute potential therapeutic targets in PC patients.

Down-regulation of MSMO1 promotes the development and progression of pancreatic cancer.

Background: Methylsterol monooxygenase 1 (MSMO1), as a completely unique tumor biomarker, plays a vital role in the malignant progression of various cancer. Until now, the potential function and pathway of MSMO1 in the development of pancreatic cancer (PC) has not been explored yet, to our knowledge.Methods: We systematically explored the detail function of MSMO1 in Epithelial-mesenchymal transition (EMT) and cell proliferation of PC in vitro and in vivo.Results: MSMO1 expression was much lower in PC tissues than that in paired normal pancreas. MSMO1 positive expression was negatively associated with T stage, lymph node metastasis and vascular permeation of PC patients. Meanwhile, positive MSMO1 expression indicated a significantly better prognosis and an independent favorable prognostic factor. MSMO1 silencing promoted cell invasion and migration via activating EMT and PI3K-AKT-mTOR pathway [p-PI3K (Tyr458), p-AKT (Ser473) and p-mTOR (Ser2448)] in Capan-2, Panc-1 and SW1990 cells. In vivo, subcutaneous tumor size was enhanced by MSMO1 silencing following with the consistent change of EMT and PI3K/AKT signaling shown in vitro. The motivation of EMT and PI3K-AKT-mTOR pathway was also demonstrated in MSMO1 silencing mouse PANC02 cells.Conclusion: Down-regulation of MSMO1 in PC was associated with advanced progression and poor prognosis of PC patients. MSMO1 acts as a tumor suppressor via inhibiting the aggressive malignant biology of PC accompanying with regulating EMT and PI3K/AKT signaling.

DGCR5 is Activated by PAX5 and Promotes Pancreatic Cancer via Targeting miR-3163/TOP2A and Activating Wnt/β-Catenin Pathway

Background: DiGeorge syndrome critical region gene 5 (DGCR5) has been shown to be associated with cancer development. However, the biological role and molecular mechanism of DGCR5 in pancreatic cancer (PC) remains largely unknown. Methods: qRT-PCR and fluorescence in situ hybridization was performed to investigate the correlation between DGCR5 expression and prognosis and clinicopathologic characteristics of PC patients. The effects of DGCR5 on PC were studied by gain & loss-of-function experiments in vitro and in vivo. RNA sequencing, bioinformatics analyses, dual-luciferase assays, chromatin immunoprecipitation assay and rescue experiments provided insights into the underlying competing endogenous RNA (ceRNA) mechanism network of DGCR5 in promoting PC progression. Results: DGCR5 was highly expressed in PC tissues compared with adjacent normal tissues and its high expression was associated with poor prognosis in PC patients. Furthermore, DGCR5 depletion inhibited the proliferation, migration and invasion by increasing apoptosis and inducing G0/G1 cell cycle arrest in vitro. Moreover, xenograft assay validated that DGCR5 promotes PC tumor growth in vivo. Mechanistically, DGCR5 was found to act as a ceRNA by sponging miR-3163 to regulate TOP2A and inhibit Wnt/β-catenin pathway. In addition, we found that DGCR5 downregulation could enhance the sensitivity of PC cells to gemcitabine, and ChIP assay showed that the transcription factor PAX5 could bind to the DGCR5 promoter and increase its transcription. Conclusions: Our study demonstrates that DGCR5 is activated by PAX5 and promotes PC progression by sponging miR-3163 to regulate TOP2A and activating wnt/β-catenin pathway, suggesting that DGCR5 may be a potential diagnostic and therapeutic target for PC.

Human CPTP promotes growth and metastasis via sphingolipid metabolite ceramide and PI4KA/AKT signaling in pancreatic cancer cells.

Pancreatic cancer (PC) is a devastating solid malignancy with a dismal prognosis. The treatment of metastatic PC is a current challenge for medical oncologists due to a lack of early detection, drug resistance, and relapse. Therefore, potential biomarkers and effective therapeutic targets for PC are urgently required. Ceramide-1-phosphate transfer protein (CPTP) is a member of the glycolipid transfer protein family, which is associated with autophagy and inflammation regulation. The roles and mechanisms of CPTP in PC have not been clarified. In this study, by RT-qPCR and immunohistochemistry analysis, we found that CPTP is highly expressed in PC and is associated with a poor prognosis in PC patients. By using cell counting kit-8, colony formation, transwell and matrigel assays in vitro, as well as xenograft model assays in vivo, we further proved that CPTP enhanced PC cells growth and metastasis. In PC cells, human CPTP promotes growth and metastasis via sphingolipid metabolite ceramide and PI4KA/AKT signaling. Sp (specific protein)-1 and Sp3 transcription factors also act as upstream positive regulators of CPTP expression in PC cells. Collectively, these findings suggested that CPTP may function as a pro-tumorigenic gene in PC cells and could be a promising therapeutic target in PC.

Positive Reciprocal Feedback of lncRNA ZEB1-AS1 and HIF-1α Contributes to Hypoxia-Promoted Tumorigenesis and Metastasis of Pancreatic Cancer.

BackgroundMany studies have reported the roles of the extracellular hypoxia microenvironment in the tumorigenesis and metastasis of multiple cancers. However, long noncoding RNAs (lncRNAs) that induce cancer oncogenicity and metastasis of pancreatic cancer (PC) under hypoxia conditions remain unclear.MethodsIn PC cells, the expression levels of lncRNAs in different conditions (normoxia or hypoxia) were compared through RNA sequencing (RNA-seq). The effects of the zinc finger E-box-binding homeobox 1 (ZEB1-AS1) antisense lncRNA on PC cells cultured in normoxia/hypoxia medium were measured through gain and loss-of-function experiments. Fluorescence in situ hybridization and luciferase reporter assays in addition to in vivo studies were utilized to explore the adaptive mechanisms of ZEB1-AS1 in the hypoxia-promoted proliferation, migration, and invasion ability of PC cells. Moreover, the level of ZEB1-AS1 and its associated targets or pathways were investigated in both PC and pancreatic normal tissues.ResultsRNA-seq revealed that ZEB1-AS1 was significantly upregulated in PC cells under hypoxia conditions. The ZEB1-AS1 expression level was closely associated with poor prognosis of PC patients. Knockdown of ZEB1-AS1 suppressed the proliferation, migration, and invasion of PC cells in vitro as well as PC xenograft tumor growth in vivo. In PC cells, RNAi-mediated reduction of ZEB1-AS1 inhibited zinc finger E-box-binding homeobox 1 (ZEB1), while ZEB1-AS1 overexpression rescued ZEB1 expression, indicating that ZEB1-AS1 promotes ZEB1 expression. Moreover, hypoxia-inducible factor-1α (HIF-1α)induced the expression of ZEB1-AS1 by binding to the ZEB1-AS1 promoter, which contains a putative hypoxia response element (HRE). Mechanistically, ZEB1-AS1 scaffolded the interaction among HIF-1α, ZEB1, and histone deacetylase 1 (HDAC1), leading to deacetylation-mediated stabilization of HIF-1α. We further revealed that ZEB1 induced the deacetylase capacity of HDAC1 to suppress the acetylation or degradation of HIF-1α, improving HIF-1α assembly. Thus, hypoxia-induced ZEB1-AS1 facilitated ZEB1 transcription and the stability of HIF-1α, which promoted the metastasis of PC cells. Clinically, dysregulated ZEB1 and HIF-1α expression was significantly correlated with histological grade, lymphatic metastasis, and distant metastasis in PC patients.ConclusionsOur results emphasized that the positive reciprocal loop of HIF-1α/ZEB1-AS1/ZEB1/HDAC1 contributes to hypoxia-promoted oncogenicity and PC metastasis, indicating that it might be a novel therapeutic target for PC.

Serum Exosomal EphA2 is a Prognostic Biomarker in Patients with Pancreatic Cancer

BackgroundPancreatic cancer (PC) is one of the worst prognoses amongst all malignant diseases. It is therefore of great significance to identify biomarkers with predictive clinical value for the prognosis and recurrence of PC.MethodsIn our study, enzyme-linked immunosorbent assays (ELISA) were used to detect the expression of Exo-EphA2 in the serum of PC patients and controls. Kaplan–Meier curve and Cox regression analyses were used to evaluate the prognostic value of Exo-EphA2 expression in patients with primary and recurrent PC.ResultsThe level of serum Exo-EphA2 was significantly higher in the PC group when compared to that of the control group. High expression of Exo-EphA2 in PC was associated with shorter overall survival (OS) and proved to be a significant negative prognostic factor in the multivariate analysis (HR = 1.04, 95% CI: 1.00–1.09, P <0.001). Additionally, we found that the level of serum Exo-EphA2 in recurrent PC patients (first recurrence < 12 months) was positively correlated with the level of Exo-EphA2 at primary diagnosis. Multivariate analysis showed that a high expression of Exo-EphA2 in recurrent PC was associated with shorter recurrence-free survival (RFS) (HR = 1.41, 95% CI: 1.10–1.70, P < 0.001).ConclusionHigh expression of serum Exo-EphA2 represents a novel biomarker for a poor prognosis in PC patients.

Expressional and Prognostic Value of S100A16 in Pancreatic Cancer Via Integrated Bioinformatics Analyses.

Studies have shown that the calcium-binding protein family S100 may play a role in the development of pancreatic cancer (PC), but the role of S100A16 in PC is still unknown. In this study, Oncomine was first used to detect the expression level and prognosis of S100A16 in PC and other tumors. The results showed that S100A16 was highly expressed in PC tissues compared with a normal pancreas, and the increased expression level may be related to poor prognosis in PC patients. The TCGA and ICGC RNA-seq data of PC patients were downloaded, and the S100A16-related differentially expressed genome (DEGs) was defined by taking the intersection of two gene sets. The GO and KEGG pathways were then analyzed. For clinical analysis, boxplots were depicted for the correlation between clinical characteristics and S100A16 expression. Then Cox regression was applied for exploring the prognostic value of S100A16 for PDAC patients. Based on the Cox regression model, we further estabished a S100A16-related risk score system to strengthen the ability to predict patients' prognosis. After integrating the risk score model and multiple clinicopathological factors, we finally established a nomogram that could predict the survival time of patients. Moreover, Gene set enrichment the effect of S100A16 expression differences on downstream biological processes. At last, using TIMER, ImmuneCellAI and GSEA we analyzed the correlation between S100A16 and pancreatic cancer immune infiltration and predicted the response of patients to checkpoint Blocker (ICB). In summary, S100A16 is involved in the occurrence and development of PC, affecting the prognosis of patients, and may have potential reference values for the immunotherapy of PC.

CMTM3 Overexpression Predicts Poor Survival and Promotes Proliferation and Migration in Pancreatic Cancer

Background: Recent evidence has shown that CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) promoted carcinogenesis and tumor progression in a variety of cancer types. The goal of our study is to investigate the association between CMTM3 and pancreatic cancer (PC).Materials and Methods: In current study, data from public databases was used to analyze CMTM3 expression in PC. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were used to investigate CMTM3 expression and determine its clinical significance in PC. Then CMTM3 promoting PC aggressiveness was demonstrated in vitro experiments by cell proliferation and migration assay. Functional and pathway enrichment analyses were performed to evaluate the potential role of CMTM3 in PC.Results: Results of qRT-PCR and IHC revealed that CMTM3 was significantly overexpressed in PC tissues. High CMTM3 expression was an independent risk factor for poor prognosis of PC patients. Overexpression of CMTM3 was associated with poor overall survival (P-value =0.031) and disease-free survival (P-value =0.0047) in the TCGA cohort. Functional and pathway enrichment analyses showed that CMTM3 were enriched in “Regulation of cell proliferation and regulation of cell differentiation, cell morphogenesis, regulation of cell differentiation, Hedgehog signaling pathway, Wnt signaling pathway, ECM-receptor interaction and pathways in cancer”. In PC cell lines, CCK8, clone formation and transwell assays showed that CMTM3 knockdown inhibited cells proliferation and migration.Conclusion: CMTM3 was overexpressed and promotes tumor aggressiveness in PC. Our findings provided a novel therapeutic target for PC.

DGCR5 is activated by PAX5 and promotes pancreatic cancer via targeting miR-3163/TOP2A and activating Wnt/β-catenin pathway.

Long noncoding RNA DiGeorge syndrome critical region gene 5 (DGCR5) has been shown to be highly associated with cancer development. However, the biological role and molecular mechanism of DGCR5 in pancreatic cancer (PC) remains largely unknown. This study aimed to explore the role of DGCR5 in PC. It was revealed that DGCR5 was highly expressed in PC tissues compared with adjacent normal tissues and was associated with poor prognosis in PC patients. Furthermore, DGCR5 depletion inhibited the proliferation, migration and invasion by increasing apoptosis and inducing G0/G1 cell cycle arrest in vitro. Moreover, xenograft assay validated that DGCR5 promotes PC tumor growth in vivo. Mechanistically, DGCR5 was found to act as a ceRNA by sponging miR-3163 to regulate DNA topoisomerase 2-alpha (TOP2A) and inhibit Wnt/β-catenin pathway. In addition, it was found that DGCR5 downregulation could enhance the sensitivity of PC cells to gemcitabine, and ChIP assay showed that PAX5 (Paired Box 5) could bind to the promoter region of DGCR5 and increase its transcription. The results of the present study indicated that DGCR5 may be a potential diagnostic biomarker and therapeutic target for PC.

MicroRNA-202 suppresses glycolysis of pancreatic cancer by targeting hexokinase 2.

Purpose: Various studies have identified miR-202 critically participated in the development of different cancers. However, the potential mechanisms underlying the carcinogenesis of pancreatic cancer (PC) still remains elusive.Methods: In the study, cell proliferation assay, colony formation assay, EdU incorporation assay, Luciferase reporter assay, lactate production, glucose consumption assay, real-time PCR and western blot were used to investigate the mechanism of hexokinase 2 (HK2) regulated by miR-202 in pancreatic cancer in vitro and in vivo.Results: Here we found that miR-202 was decreased in the PC tissues, and its low expression was correlated with a poor prognosis of PC patients. Overexpression of miR-202 in PC cells reduced cell proliferation and tumorigenesis by impairing glycolysis, while downregulation of miR-202 promoted the cells proliferative capacity. Mechanically, we demonstrated that HK2, an enzyme that catalyzes the irreversible rate-limiting step of glycolysis, as the direct target of miR-202. Overexpression of miR-202 suppressed both the mRNA and protein levels of HK2, whereas re-introduction of HK2 abrogated miR-202-mediated glycolytic inhibition. In addition, the expression of miR-202 was negatively associated with HK2 level in a cohort of PC tissues.Conclusion: Our findings validate the mechanism that miR-202 reprograms the metabolic process to promote PC progression, thus providing potential prognostic predictors for PC patients.

Long noncoding RNA TSLNC8 enhances pancreatic cancer aggressiveness by regulating CTNNB1 expression via association with HuR.

Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. Tumor suppressor long noncoding RNA on chromosome 8p12 (TSLNC8) is a newly identified long noncoding RNA (lncRNA) and play an important role in human cancers. However, the function and molecular mechanism of TSLNC8 in PC progression remain to be elucidated. Our results showed a significant increase of TSLNC8 expression in PC tissues and cell lines. Upregulation of TSLNC8 expression in PC tissues was closely correlated with TNM stage, distant and lymph node metastasis, and poor prognosis of PC patients. Functional experiments demonstrated that TSLNC8 promoted PC cells proliferation and invasion in vitro, and enhanced PC growth and metastasis in vivo. Mechanistically, TSLNC8 associated with HuR, promoted the binding of HuR with CTNNB1 mRNA and increased the stability of CTNNB1 mRNA, thus activating WNT/β-catenin signaling pathway. Taken together, our present study revealed that oncogenic lncRNA TSLNC8 positively regulate PC growth and metastasis via HuR-mediated mRNA stability of CTNNB1, extending the understanding of PC pathogenesis regulated by lncRNAs.

MiR-504 and miR-205 May be Used to Evaluate Prognosis and Chemotherapeutic Effect of Pancreatic Cancer Patients

To explore the value of miR-504 and miR-205 in evaluating the prognosis and chemo-therapeutic effect of pancreatic cancer (PC) patients. Ninety-six PC patients who came to our hospital from March 2015 to February 2017 were selected as the research group (RG), and 96 healthy subjects during the same period were considered as the control group (CG). Serum miR-504 and miR-205 of subjects in the two groups were detected and compared by Rt-PCR, and the miR-504 and miR-205 expression levels in serum of PC patients before and after chemotherapy were analyzed, so did the relationship between miR-504, miR-205 and prognosis of patients. The miR-504 and miR-205 expression levels in serum of PC patients were dramatically higher than those of healthy people (P[ 0.05), and the expression levels in serum of those in the chemotherapy-effective group were dramatically lower than those of those in the chemotherapy-ineffective group (P[ 0.05). Moreover, the 3-year mortality of patients with high expression of miR-504 and miR-205 was higher than that of those with low expression (P[ 0.05), and the miR-504 and miR-205 expression levels in dead patients were higher than those in living patients. miR-504 and miR-205 had high predictive value for poor prognosis of PC patients. Univariate analysis identified that their poor prognosis was related to pathological stage, lymph node metastasis, differentiation degree and expression of miR-504 and miR-205 (P[ 0.05). Cox multivariate analysis identified that pathological stage, lymph node metastasis, differentiation degree and expression of miR-504 and miR-205 were independent risk factors for poor prognosis (P[ 0.05).DLX6-AS1 is highly expressed in the serum of PC patients, and it can evaluate the chemotherapeutic effect and predict the prognosis. So, it may be used as a new target direction for evaluating the chemotherapeutic effect and predicting the prognosis of patients.

Musashi2 promotes the progression of pancreatic cancer through a novel ISYNA1-p21/ZEB-1 pathway.

Our previous studies found overexpression of Musashi2 (MSI2) conduced to the progression and chemoresistance of pancreatic cancer (PC) by negative regulation of Numb and wild type p53 (wtp53). Now, we further investigated the novel signalling involved with MSI2 in PC. We identified inositol‐3‐phosphate synthase 1 (ISYNA1) as a novel tumour suppressor regulated by MSI2. High MSI2 and low ISYNA1 expression were prevalently observed in 91 PC tissues. ISYNA1 expression was negatively correlated with MSI2 expression, T stage, vascular permeation and poor prognosis in PC patients. What's more, patients expressed high MSI2 and low ISYNA1 level had a significant worse prognosis. And in wtp53 Capan‐2 and SW1990 cells, ISYNA1 was downregulated by p53 silencing. ISYNA1 silencing promoted cell proliferation and cell cycle by inhibiting p21 and enhanced cell migration and invasion by upregulating ZEB‐1. However, MSI2 silencing upregulated ISYNA1 and p21 but downregulated ZEB‐1, which can be rescued by ISYNA1 silencing. Moreover, reduction of cell migration and invasion resulting from MSI2 silencing was significantly reversed by ISYNA1 silencing. In summary, MSI2 facilitates the development of PC through a novel ISYNA1‐p21/ZEB‐1 pathway, which provides new gene target therapy for PC.

Reduced expression of CDH1 and its prognostic value in pancreatic cancer: a meta-analysis

IntroductionIn this study, we aimed to focus on reduced expression of E-cadherin (CDH1) and its prognostic value in pancreatic cancer (PC) using a meta-analysis.Material and methodsFor this purpose, the PubMed and EMBASE databases were searched from inception until September 1, 2018. Hazard ratio (HR) and 95% confidence interval (CI) were pooled to evaluate the association between CDH1 expression and overall survival (OS); also, odds ratio (OR) and 95% CI were used to assess the correlation between clinicopathological features and CDH1 expression in PC patients. Data from a total of 1805 patients from 16 articles were used in this meta-analysis.ResultsPC patients with decreased expression of CDH1 had a shorter OS (HR = 1.25, 95% CI: 1.09–1.41), without a significant heterogeneity (I2 = 27.1%, p = 0.151). The down-regulated expression of CDH1 was strongly associated with tumour grade (OR = 1.80, 95% CI: 1.07–3.03).ConclusionsDown-regulated expression of CDH1 has potential as a predictive marker of poor prognosis in PC patients. However, further high-quality and large-scale clinical studies are required to validate our findings.

LINC00473 functions as an oncogene and predicts poor prognosis in pancreatic cancer via the cAMP/β-catenin axis.

To investigate the expression and function of LINC00463 in pancreatic cancer (PC), and to demonstrate the relationship between LINC00473 expression and clinical pathological characteristics and prognosis of PC. Expressions of LINC00473 in PC tissues and cell lines were detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). LINC00473 siRNA was synthesized to knock down the LINC00473 expression in PANC-1 cells. Proliferation, invasion, and migration abilities of experimental cells were analyzed using cell counting kit-8 (CCK-8) assay and transwell assay, respectively. cAMP activity was detected and protein expression of β-catenin was measured to explain the underlying mechanism of LINC00473 in PC. The prognosis and clinical pathological features of PC patients were illustrated. LINC00473 was highly expressed in PC tissues and cells. Higher level of LINC00473 was relative with larger tumor size, worse tumor node metastasis (TNM) stage, worse tumor differentiation, higher rates of perineural invasion, and lymphatic invasion. Knockdown of LINC00473 significantly inhibited cell growth, invasion, and migration of PANC-1 cells. LINC00473 activated cAMP and then promoted the phosphorylation of β-catenin to promote the progression of PC. Furthermore, high expression of LINC00473 and β-catenin remarkedly indicated poor prognosis of PC patients. LINC00473 was upregulated in PC tissues and cells, indicating a poor prognosis and clinical pathological features of PC. It promoted PC progression via activating the cAMP/β-catenin axis, which provided a novel target for the prediction for PC diagnosis, biological therapy, and prognosis.