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Objective To investigate the expression of LncRNA LINC00857 in pancreatic cells and the effect of lncRNA LINC00857 down-regulation on proliferation, migration and apoptosis of pancreatic cancer PANC-1 cells and possible mechanism. Methods The lentiviral vector GV112 was constructed and infected PANC-1 cells to obtain experimental group, while the blank plasmid was transfected as a negative control group and the cells without intervention were taken as normal control group. CCK-8 assay, Transwell assay, scratch test, flow cytometry, Western blot were used to detect the effect of LINC00857 down-regulation on cell proliferation, migration, apoptosis, cell cycle and EMT-related proteins. Results LINC00857 expression in pancreatic cancer cells were significantly higher than that in normal pancreatic epithelial cells (P < 0.001). Knockdown of LINC00857 could significantly inhibit the proliferation and migration of PANC-1 cells (P < 0.0001); compared with the negative control group, the apoptosis rates of cells in the experimental groups were significantly increased (P < 0.05), the number of cells in G0/G1 phase increased (P < 0.01), the number of cells in S phase decreased (P < 0.05), and the cells were blocked in the G1 phase, E-cadherin expression was significantly up-regulated (P < 0.05) and N-cadherin and Vimentin expression were significantly down-regulated (N-cadherin: P < 0.01, Vimentin: P < 0.05). Conclusion LINC00857 can promote proliferation and migration of PANC-1 cells and inhibit its apoptosis by regulating G1/S phase transition and EMT signaling pathway.

Objective To investigate the expression of MYEOV in human pancreatic cancer cells and its effect on the proliferation and migration of pancreatic cancer SW1990 cells after knockdown. Methods The lentiviral vector GV248 was constructed and infected SW1990 cells to obtain two experimental groups (SW1990-sh1 and SW1990-sh2), while the blank plasmid was transfected as a negative control group and the untreated cells were taken as blank control group. MYEOV mRNA and protein expression were detected by qPCR and Western blot before and after transfection. The cells proliferation was determined by CCK-8 assay; the cell migration ability was analyzed by scratch test; The mRNA expression of SMADs in the TGF-β/SMAD signaling pathway was detected by qPCR. Results Compared with the pancreatic ductal epithelium cell line HPDE6, the mRNA expression of MYEOV in six pancreatic cancer cells were significantly increased (P < 0.01). However, low expression of MYEOV protein was detected only in PANC-1 and SW1990 cells. The mRNA and protein expression of MYEOV in the experimental groups were significantly downregulated. The proliferation and migration of SW1990 cells were lower than the control group (P < 0.001). MYEOV knockdown could reduce the mRNA expression of SMAD1, SMAD4, SMAD5 and SMAD9 in TGF-β pathway, while the expression of SMAD2, SMAD3 and SMAD7 mRNA were only down-regulated in the SW1990-sh2 group (P < 0.001). Conclusion MYEOV mRNA is overexpressed in pancreatic cancer cells. MYEOV could promote the proliferation and migration of pancreatic cancer cells via TGF-β/SMAD pathway.

Plakophilin 3 (PKP3) affects cell signal transduction and cell adhesion and performs a crucial function in tumorigenesis. The current investigation evaluated the predictive significance and underlying processes of PKP3 within pancreatic cancer (PC) tissues. The assessment of differences in PKP3 expression was conducted through an analysis of RNA-seq data acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, clinical samples were collected to validate the findings. The predictive significance of PKP3 was investigated by analyzing survival data derived from TCGA and clinical specimens. PKP3′s biological function was assessed via phenotypic experiments after the suppression of PKP3 expression within PC cells. Functional enrichment analysis, encompassing KEGG, GO, and GSEA, was employed to assess the underlying mechanism of PKP3. Immune infiltration analysis was conducted in the present investigation to determine the association between PKP3 and tumor-infiltrating immune cells (TICs). In PC tissues, PKP3 expression was abnormally upregulated and correlated with a negative prognosis in individuals with PC. PKP3 can promote the progression, migration, and invasive capacity of PC cells and is relevant to the regulation of the PI3K–Akt and MAPK signaling pathways. Immune infiltration analysis demonstrated that PKP3 impeded CD8+ T-cell infiltration and immune cytokine expression within the tumor microenvironment. The PKP3 protein was identified as a prospective independent predictive indicator and represents a viable approach for immunotherapy in the context of PC. PKP3 may impact prognosis by broadly inhibiting immune cell infiltration and promoting the activation of tumor-associated signaling pathways. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages M2 (TAM2), which are highly prevalent infiltrating immune cells in the stroma of pancreatic cancer (PC), have been found to induce an immunosuppressive tumor microenvironment, thus enhancing tumor initiation and progression. However, the immune therapy response and prognostic significance of regulatory genes associated with TAM2 in PC are currently unknown. Based on TCGA transcriptomic data and single-cell sequencing data from the GEO database, we identified TAM2-driven genes using the WGCNA algorithm. Molecular subtypes based on TAM2-driven genes were clustered using the ConsensusClusterPlus algorithm. The study constructed a prognostic model based on TAM2-driven genes through Lasso-COX regression analysis. A total of 178 samples obtained by accessing TCGA were accurately categorized into two molecular subtypes, including the high-TAM2 infiltration (HMI) cluster and the low-TAM2 infiltration (LMI) cluster. The HMI cluster exhibits a poor prognosis, a malignant tumor phenotype, immune-suppressive immune cell infiltration, resistance to immunotherapy, and a high number of genetic mutations, while the LMI cluster is the opposite. The prognostic model composed of six hub genes from TAM2-driven genes exhibits a high degree of accuracy in predicting the prognosis of patients with PC and serves as an independent risk factor. The induction of TAM2 was employed as a means of verifying these six gene expressions, revealing the significant up-regulation of BCAT1, BST2, and MERTK in TAM2 cells. In summary, the immunophenotype and prognostic model based on TAM2-driven genes offers a foundation for the clinical management of PC. The core TAM2-driven genes, including BCAT1, BST2, and MERTK, are involved in regulating tumor progression and TAM2 polarization, which are potential targets for PC therapy. [ABSTRACT FROM AUTHOR]

Ena-VASP-like (EVL), a member of the Enabled/vasodilator stimulated phosphoprotein family, is functionally expressed in various cancers. This study explored the prognostic value and potential mechanism of EVL in pancreatic cancer (PC). RNA-seq obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to evaluate EVL expression differences, and clinical samples were collected for validation. The prognostic value of EVL was evaluated by survival data obtained from TCGA and clinical samples. The biological pathways involved in EVL were evaluated by functional enrichment analysis such as GO, KEGG, and GSEA. We used immune infiltration analysis to estimate the correlation between EVL and tumor-infiltrating immune cells (TICs). The expression of EVL is down-regulated in PC tissues, which is an independent factor affecting survival time. Survival analysis suggested EVL-high expression was associated with good prognosis in PC patients. The results of the enrichment analysis suggested that the biological function of EVL was closely related to the immune mechanism. Tumor immune infiltration analysis showed that high expression of EVL was accompanied by high levels of immune infiltration. Furthermore, EVL was strongly correlated with the content of immune cells such as CD8+ T cells, B cells, regulatory T cells, CD4+ Tem cells, and follicular Th cells. EVL is a potential independent prognostic marker and immunotherapy target for PC. Mechanistically, EVL may affect the prognosis by extensively promoting immune cell infiltration, including strengthening the anti-tumor immune response of CD8+ T cells. [ABSTRACT FROM AUTHOR]

The liver is the most prevalent location of distant metastasis for pancreatic cancer (PC), which is highly aggressive. Pancreatic cancer with liver metastases (PCLM) patients have a poor prognosis. Furthermore, there is a lack of effective predictive tools for anticipating the diagnostic and prognostic techniques that are needed for the PCLM patients in current clinical work. Therefore, we aimed to construct two nomogram predictive models incorporating common clinical indicators to anticipate the risk factors and prognosis for PCLM patients. Clinicopathological information on pancreatic cancer that referred to patients who had been diagnosed between the years of 2004 and 2015 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression analyses and a Cox regression analysis were utilized to recognize the independent risk variables and independent predictive factors for the PCLM patients, respectively. Using the independent risk as well as prognostic factors derived from the multivariate regression analysis, we constructed two novel nomogram models for predicting the risk and prognosis of PCLM patients. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, the consistency index (C-index), and the calibration curve were then utilized to establish the accuracy of the nomograms' predictions and their discriminability between groups. Using a decision curve analysis (DCA), the clinical values of the two predictors were examined. Finally, we utilized Kaplan–Meier curves to examine the effects of different factors on the prognostic overall survival (OS). As many as 1898 PCLM patients were screened. The patient's sex, primary site, histopathological type, grade, T stage, N stage, bone metastases, lung metastases, tumor size, surgical resection, radiotherapy, and chemotherapy were all found to be independent risks variables for PCLM in a multivariate logistic regression analysis. Using a multivariate Cox regression analysis, we discovered that age, histopathological type, grade, bone metastasis, lung metastasis, tumor size, and surgery were all independent prognostic variables for PCLM. According to these factors, two nomogram models were developed to anticipate the prognostic OS as well as the risk variables for the progression of PCLM in PCLM patients, and a web-based version of the prediction model was constructed. The diagnostic nomogram model had a C-index of 0.884 (95% CI: 0.876–0.892); the prognostic model had a C-index of 0.686 (95% CI: 0.648–0.722) in the training cohort and a C-index of 0.705 (95% CI: 0.647–0.758) in the validation cohort. Subsequent AUC, calibration curve, and DCA analyses revealed that the risk and predictive model of PCLM had high accuracy as well as efficacy for clinical application. The nomograms constructed can effectively predict risk and prognosis factors in PCLM patients, which facilitates personalized clinical decision-making for patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression, function and clinical significance of maternal leucine zipper kinase (MELK) in pancreatic cancer. Methods: The expression of MELK in pancreatic cancer was analyzed and the possible molecular mechanism of MELK in pancreatic cancer was predicted by bioinformatics. The clinical data of 45 patients with pancreatic cancer undergoing surgical treatment in the First Hospital of Lanzhou University were retrospectively analyzed. Immunohistochemistry was used to explore the MELK expression levels in pancreatic cancer tissues and normal para-cancerous tissues, and its relationship with clinical pathological characteristics was also analyzed. The postoperative recurrence time of patients was collected through outpatient records and telephone follow-up to explore the relationship between MELK expression and postoperative recurrence time. Results: MELK mRNA was highly expressed in pancreatic cancer tissues and correlated with the overall survival rate and postoperative recurrence time. Multivariate Cox analysis showed that the MELK gene could be used as an independent prognostic factor in patients with pancreatic cancer. Functional enrichment suggests that MELK is involved in multiple cancer-related functional pathways and is positively correlated with the pathogenic molecules of pancreatic cancer. Immunohistochemistry results showed that MELK in pancreatic cancer tissues was significantly higher than that in adjacent normal tissues. The expression of MELK in pancreatic cancer tissues was correlated with tumor size. Conclusion: The MELK gene is highly expressed in pancreatic cancer tissues and is associated with patients' prognosis. MELK plays a role in the progression of pancreatic cancer and is expected to become a potential biomarker and therapeutic target of pancreatic cancer. [ABSTRACT FROM AUTHOR]

The signal transducer and activator of transcription (STAT) is a family of intracellular cytoplasmic transcription factors involved in many biological functions in mammalian signal transduction. Among them, STAT3 is involved in cell proliferation, differentiation, apoptosis, and inflammatory responses. Despite the advances in the treatment of pancreatic cancer in the past decade, the prognosis for patients with pancreatic cancer remains poor. STAT3 has been shown to play a pro-cancer role in a variety of cancers, and inhibitors of STAT3 are used in pre-clinical and clinical studies. We reviewed the relationship between STAT3 and pancreatic cancer and the latest results on the use of STAT3 inhibitors in pancreatic cancer, with the aim of providing insights and ideas around STAT3 inhibitors for a new generation of chemotherapeutic modalities for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic body tail carcinoma (PBTC) is a relatively few pancreatic cancer in clinical practice, and its specific clinicopathological features and prognosis have not been fully described. In this study, we aimed to create a nomogram to predict the overall survival (OS) of patients with advanced PBTC.Methods: We extracted clinical and related prognostic data of advanced PBTC patients from 2000 to 2018 from the Surveillance, Epidemiology, and End Results database. Independent prognostic factors were selected using univariate and multivariate Cox analyses, and a nomogram was constructed using R software. The C-index, area under the curve (AUC) of receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to assess the clinical utility of the nomogram. Finally, OS was assessed using the Kaplan-Meier method.Results: A total of 1256 patients with advanced PBTC were eventually included in this study. Age, grade, N stage, M stage, surgery, and chemotherapy were identified as independent risk factors using univariate and multivariate Cox regression analyses (p < 0.05). In the training cohort, the calibration index of the nomogram was 0.709, while the AUC values of the nomogram, age, grade, N stage, M stage, surgery, and chemotherapy were 0.777, 0.562, 0.621, 0.5, 0.576, 0.632, and 0.323, respectively. Meanwhile, in the validation cohort, the AUC values of the nomogram, age, grade, N stage, M stage, surgery, and chemotherapy were 0.772, 0.551, 0.629, 0.534, 0.577, 0.606, and 0.639, respectively. Good agreement of the model in the training and validation cohorts was demonstrated in the calibration and DCA curves. Univariate survival analysis showed a statistically significant effect of age, grade, M stage, and surgery on prognosis (p < 0.05).Conclusion: Age, grade, M stage, and surgery were independently associated with OS, and the established nomogram was a visual tool to effectively predict OS in advanced PBTC patients. [ABSTRACT FROM AUTHOR]

Intermediate between apoptosis and necrosis, necroptosis is a regulated caspase-independent programmed cell death that induces an inflammatory response and mediates cancer development. As our understanding improves, its role in the physiopathology of numerous diseases, including pancreatic diseases, has been reconsidered, and especially in pancreatitis and pancreatic cancer. However, the exact pathogenesis remains elusive, even though some studies have been conducted on these diseases. Its unique mechanisms of action in diseases are expected to bring prospects for the treatment of pancreatic diseases. Therefore, it is imperative to further explore its molecular mechanism in pancreatic diseases in order to identify novel therapeutic options. This article introduces recent related research on necroptosis and pancreatic diseases, explores necroptosis-related molecular pathways, and provides a theoretical foundation for new therapeutic targets for pancreatic diseases. [ABSTRACT FROM AUTHOR]

Antihypertensive medications may have some impacts on cancer. The influence of antihypertensive medications, including angiotensin converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs) and diuretics, on patients with pancreatic cancer (PC) remains controversial. This meta-analysis was conducted to investigate whether antihypertensive medications had a negative effect on the prognosis of patients with PC. The PubMed, Embase, Web of Science and the Cochrane Library databases were searched up to 30 November 2021. The Newcastle-Ottawa scale was used to evaluate the quality of each study. This meta-analysis was registered with PROSPERO (CRD42021279169) and was carried out by using RevMan 5.3. Twelve studies with 120,549 patients were included in this study. ACEIs/ARBs [HR = 0.89, 95% CI (0.70–1.14)], CCB (HR = 0.69, 95% CI (0.47–0.99)], beta-blockers [HR = 0.95, 95% CI (0.84–1.07)] and diuretics [HR = 1.08, 95% CI (0.91–1.29)] use had no effects on overall survival among patients with PC (all P ≥ 0.05). Antihypertensive medication will not have a negative effect on overall survival in patients with PC. PC patients with hypertension should continue to use antihypertensive medications to reduce the morbidity and mortality of cardiovascular events. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most common malignant tumors in the digestive system with a poor prognosis. Accordingly, better understanding of the molecular mechanisms and innovative therapies are warranted to improve the prognosis of this patient population. In addition to playing a crucial role in coagulation, platelets reportedly contribute to the growth, invasion and metastasis of various tumors, including pancreatic cancer. This narrative review brings together currently available evidence on the impact of platelets on pancreatic cancer, including the platelet-related molecular mechanisms of cancer promotion, pancreatic cancer fibrosis, immune evasion, drug resistance mechanisms, thrombosis, targeted platelet therapy, combined radiotherapy and chemotherapy treatment, platelet combined with nanotechnology treatment and potential applications of pancreatic cancer organoids. A refined understanding of the role of platelets in pancreatic cancer provides the foothold for identifying new therapeutic targets. [ABSTRACT FROM AUTHOR]

The human body is thoroughly colonized by a wide variety of microorganisms, termed microbiota. Pancreatic cancer, one of the most aggressive forms of cancer, is no exception. The microbiota of pancreatic cancer largely influences and even dominates the occurrence, development and outcome of pancreatic cancer in many ways. Studies have shown that microbiota could change the malignant phenotype and prognosis of pancreatic cancer by stimulating persistent inflammation, regulating the antitumor immune system, changing the tumor microenvironment and affecting cellular metabolism. This is why the association of the microbiota with pancreatic cancer is an emerging area of research that warrants further exploration. Herein, we investigated the potential microbial markers of pancreatic cancer, related research models, the mechanism of action of microbiota in pancreatic cancer, and pancreatic cancer-microbiota-related treatment. [ABSTRACT FROM AUTHOR]

The pathogenesis and etiology of pancreatic cancer remain to be fully elucidated; therefore, associated investigations are required to improve the outcome and prognosis of patients. In the present study, the effects of the overexpression of p16ink4a on the Wnt/β-catenin signaling pathway were investigated in pancreatic cancer cell lines. Two pancreatic cancer cell lines, Bxpc-3 and Miapaca-2, characterized by low expression of p16ink4a, were transfected with the pc-DNA3.0-p16ink4a plasmid. After 24 h, Reverse transcription-polymerase chain reaction and western blot analyses were performed to evaluate the expression of p16ink4a, β-catenin, which is a key molecule in the Wnt/β-catenin signaling pathway, c-myc and cyclin D1, which are molecules downstream of β-catenin. The expression of p16ink4a was significantly upregulated in the transfected cells. Consequently, the expression of β-catenin was inhibited, whereas the expression levels of c-myc and cyclin D1 were not altered significantly. The increased expression of p16ink4a may affect the activity of Wnt/β-catenin signaling through modulation of the expression of β-catenin. The results of the present study provide information for the future development of targeted treatments for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Cellular senescence is a state of growth arrest where nonproliferative cells accumulate over time in the aging microenvironment under multiple external factors. Senescent cells exert a double-edged sword effect in an autocrine or paracrine manner: physiologically, they contribute to tissue development, prevent the multiplication of damaged cells and contribute to tissue repair and tumor suppression while favoring the onset of age-related diseases, including tumors. The microbiota in human tissues is intricately linked to cellular senescence and is reportedly present in the tissues of various tumors (including pancreatic tumors), closely associated with tumorigenesis and progression. The microbiota can induce cells to undergo senescence, and their long-term effects can assist senescent cells in transforming and successfully escaping senescence, contributing to tumorigenesis and progression. Here, we focus on the correlation between the microbiota, cellular senescence, and pancreatic cancer to provide novel ideas for the study and therapy of pancreatic cancer. • Cell senescence is a double-edged sword, maintaining normal cell development and promoting tumor development. • The microbiota plays an important role in human diseases, including tumors, and can even dominate the generation and development of tumors. • Microbiota can induce cellular senescence or assist cells to circumvent cellular senescence, which has important implications in tumor generation, progression and therapy. [ABSTRACT FROM AUTHOR]