Mucin 5AC Serves as the Nexus for β-Catenin/c-Myc Interplay to Promote Glutamine Dependency During Pancreatic Cancer Chemoresistance

et al. 2022

Front. Oncol.

BackgroundPancreatic cancer (PC) is a serious disease with high mortality. The tumor microenvironment plays a key role in the occurrence and development of PC. The purpose of this study is to analyze trends by year, country, institution, journal, reference and keyword in publications on the PC microenvironment and to predict future research hotspots.MethodsThe Web of Science Core Collection was used to search for publications. We analyzed the contributions of various countries/regions, institutes, and authors and identified research hotspots and promising future trends using the CiteSpace and VOSviewer programs. We also summarized relevant completed clinical trials.ResultsA total of 2,155 papers on the PC microenvironment published between 2011 and 2021 were included in the study. The number of publications has increased every year. The average number of citations per article was 32.69. The USA had the most publications, followed by China, and a total of 50 influential articles were identified through co-citation analysis. Clustering analysis revealed two clusters of keywords: basic research and clinical application. The co-occurrence cluster analysis showed glutamine metabolism, carcinoma-associated fibroblasts, oxidative phosphorylation as the highly concerned research topics of basic research in recently. The three latest hot topics in clinical application are liposomes, endoscopic ultrasound and photodynamic therapy.ConclusionThe number of publications and research interest have generally increased, and the USA has made prominent contributions to the study of the tumor microenvironment of PC. The current research hotspots mainly focus on energy metabolism in the hypoxic tumor microenvironment, cancer associated fibroblasts in regulating the tumor microenvironment, accurate diagnosis, drug delivery and new treatments.

Section: Discussionmentioning

confidence: 99%

Emerging Trends and Research Foci in Tumor Microenvironment of Pancreatic Cancer: A Bibliometric and Visualized Study

Liu²,

et al. 2022

Front. Oncol.

“…Researchers in the University of Nebraska Medical Center recently found that MUC5AC, as a link between β-catenin and c-Myc, increased glutamine uptake, which was used in pancreatic cancer cells. Co-targeting MUC1 with gemcitabine can improve the therapeutic effect of pancreatic cancer [ 51 ]. Therefore, mucin can be used as a biomarker to predict the prognosis of patients and as a therapeutic target to improve the efficacy of pancreatic cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Association of mucin family members with prognostic significance in pancreatic cancer patients: A meta-analysis

Zhang

et al. 2022

PLoS ONE

Objective The role of biomarkers in the early diagnosis and prognosis prediction of tumors has been paid more and more attention by researchers. Mucins are markers that have been found to have an abnormal expression in many tumors in recent years, which have been proved to have a predictive effect on the prognosis of tumors such as cholangiocarcinoma and colon cancer. However, whether it can predict the prognosis of pancreatic cancer remains unknown. The purpose of our study is to investigate whether the mucins and their subtypes are related to the prognosis of patients with pancreatic cancer. Methods We systematically searched the Pubmed, Embase, and Cochrane Library for all eligible studies on the relationship between mucin and the prognosis of patients with pancreatic cancer up to November 2021. We used R 4.12 to calculate the combined risk ratio (HR) and 95% confidence interval (CI). For studies that did not provide HR values, we used scientific methods to calculate their values as accurately as possible. We used fixed effect model due to low heterogeneity. Subgroup analysis and sensitivity analysis were used to study heterogeneity. The funnel plot and Egger test were used to test whether the publication bias existed. The trim and filling method were used to evaluate the impact of publication bias on the results of the study. Results A total of 18 studies were included in this meta-analysis, including 4 subtypes of mucin family members and 1643 patients. There was a slight heterogeneity between studies (I2 = 24.4%, P = 0.14). Meta-analysis showed that MUC4 (HR = 2.04, 95%CI 1.21;3.45), MUC16 (HR = 2.10, 95%CI 1.31;3.37), and whole mucin (HR = 1.32, 95%CI 1.07;1.63). The expression level was negatively correlated with the prognosis of pancreatic cancer patients, MUC1 (HR = 1.09, 95%CI 0.77;1.54), MUC5 (HR = 1.03, 95%CI 0.47;2.25) The expression level was not related to the prognosis of pancreatic cancer patients. Conclusion The meta-analysis demonstrated that the overall expression level of mucin and the expression levels of MUC4 and MUC16 were important prognostic predictors for pancreatic cancer patients. MUC1 and MUC5 had no predictive value for the prognosis of pancreatic cancer patients. Future studies should validate these and other promising biomarkers. Trial registration PROSPERO registration number is CRD42021291962. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021291962.

“…Immunohistochemical staining (IHC) was performed as previously described [ 9 ]. Briefly, human bladder tissue specimens were fixed in formalin and then embedded in paraffin and sliced.…”

Section: Methodsmentioning

confidence: 99%

NXPH4 Promotes Gemcitabine Resistance in Bladder Cancer by Enhancing Reactive Oxygen Species and Glycolysis Activation through Modulating NDUFA4L2

Wang

Zhang

et al. 2022

Cancers

Bladder cancer is one of the most prevalent kinds of cancer worldwide, and resistance to gemcitabine is a major problem for patients. The pathogenesis of bladder cancer and mechanism of resistance to chemotherapy remain to be explored. Through bioinformatics analysis, we first found that NXPH4 was independently related to the prognosis of patients with bladder cancer. Through wound healing assays, transwell invasion assays, and plate clone formation assays, we found that NXPH4 promoted the proliferation, migration, and invasion of bladder cancer cells. The induced gemcitabine resistance cell line also showed a higher expression of NXPH4. A glycolytic activity assay demonstrated that the expression of NXPH4 was positively related to glycolysis. A higher level of reactive oxygen species caused by enhanced levels of NXPH4 was found in gemcitabine-resistant cell lines. NDUFA4L2, glycolysis, and reactive oxygen species were shown to be essential for NXPH4-regulated functions through rescue assays in cell lines. The roles of NXPH4-regulated glycolysis, gemcitabine resistance, and NDUFA4L2 were validated in vivo as well. Our results imply that NXPH4 contributes to the proliferation, migration, and invasion of bladder cancer by maintaining the stability of NDUFA4L2 and consequently activating reactive oxygen species and glycolysis.