Coordinated silencing of the Sp1-mediated long noncoding RNA MEG3 by EZH2 and HDAC3 as a prognostic factor in pancreatic ductal adenocarcinoma

Objective:Pancreatic ductal adenocarcinoma(PDAC)is a disease with high mortality.Many so-called"junk"noncoding RNAs need to be discovered in PDAC.The purpose of this study was therefore to investigate the function and regulatory mechanism of the long noncoding RNA MEG3 in PDAC.Methods:The Gene Expression Omnibus database(GEO database)was used to determine the differential expression of long noncoding RNAs in PDAC,and MEG3 was selected for subsequent verification.Tissue and cell samples were used to verify MEG3 expression,followed by functional detection in vitro and in vivo.Microarrays were used to characterize long noncoding RNA and mRNA expression profiles.Competing endogenous RNA analyses were used to detect differential MEG3 and relational miRNA expression in PDAC.Finally,promoter analyses were conducted to explain the downregulation of MEG3 PDAC.Results:We generated a catalogue of PDAC-associated long noncoding RNAs in the GEO database.The ectopic expression of MEG3 inhibited PDAC growth and metastasis in vitro and in vivo,which was statistically significant(P<0.05).Microarray analysis showed that multiple microRNAs interacted with MEG3.We also showed that MEG3,as a competing endogenous RNA,directly sponged miR-374a-5p to regulate PTEN expression.The transcription factor,Sp1,recruited EZH2 and HDAC3 to the promoter and transcriptionally repressed MEG3 expression.Finally,clinical data showed that MEG3 and miR-374a-5p expressions were correlated with clinicopathological features.Statistically,Sp1,EZH2,HDAC3,and miR-374 a-5p were negatively correlated with MEG3(P<0.05).Conclusions:Reduced MEG3 levels played a crucial role in the PDAC malignant phenotype,which provided insight into novel and effective molecular targets of MEG3 for pancreatic cancer treatment.

Chinese Medical Association consensus for standardized diagnosis and treatment of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(pNENs)are rare and highly heterogeneous tumors originating from pluripotent stem cells with neuroendocrine differentiation in the pancreas,constituting approximately 3%of all pancreatic tumors.^([1])The global incidence of pNENs has been increasing recently,and most cases are sporadic and more common in women.^([1,2])pNENs are clinically divided into functioning and nonfunctioning tumors depending on whether the tumors are accompanied by a clinical syndrome related to specific hormone overproduction.

Characterization of DNA damage response deficiency in pancreatic cancer patients from China

To the editor,Pancreatic ductal adenocarcinoma(PDAC)has the worst prognosis among all common malignant solid tumors,with a 5-year overall survival(OS)rate of less than 10%[1].Few effective targets for anticancer ther-apy have been confirmed in pancreatic cancer.Recently,it was substantiated that pancreatic cancer patients carry-ing deleterious mutations of the DNA damage response(DDR)genes are more likely to benefit from platinum-based chemotherapy[2]and poly(adenosine diphosphate-ribose)polymerase(PARP)inhibitor[3].

The real-world study of the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer in China

Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are lacking.As such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(including locally advanced and metastatic disease)in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database.Methods:A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database.The entire course of real-world pancreatic cancer management was analyzed.Results:The proportion of patients with advanced pancreatic cancer was higher among males than females(62.4%vs 37.6%,respectively).Patients typically had a history of hypertension(30.8%),diabetes(21.6%),and cholangitis(20.2%).Abdominal pain(51.6%),abdominal distension(27.1%),jaundice(20.1%),and weight loss(16.3%)were the main symptoms observed in patients with advanced pancreatic cancer in this cohort.Serum carbohydrate antigen(CA)19-9 is one of the most common tumor markers.In the present study,2562 patients underwent first-line therapy.The median progression-free survival(PFS)for patients undergoing first-line therapy was 4.1 months.The major options for first-line therapy included gemcitabine(GEM)plus S-1(GS/X)(23.4%),nab-paclitaxel plus GEM(AG)(18.1%),oxaliplatin,irinotecan,and leucovorin-modulated fluorouracil(FOLFIRINOX;11.9%),nab-paclitaxel plus S-1(AS)(8.9%),and GEM combined with oxaliplatin/cisplatin(GEMOX/GP)(7.6%).The AS and GS/X regimens were associated with the highest PFS rates.Conclusion:This is the first study to report multicenter,real-world data regarding advanced pancreatic cancer in China.Results revealed that real-world treatment options differed from guideline recommendations,and PFS was shorter than that in previously reported data.Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.