Introduction: Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic malignancies which presents different biological and clinical features with classic pancreatic ductal adenocarcinoma. However, no comprehensive comparative analysis of genomics and tumor microenvironment (TME) between PASCs and PDACs has been reported. This study is to determine genomic and TME difference between PASCs and PDACs via bioinformatical approach. Method: RNA-seq, mutation and clinical data of ICGC (International Cancer Genome Consortium) cohort were downloaded and collected from CBioPortal website. R package maftools and GenVisR were applied to analyze mutated genes and Deseq2 was used to screen differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI)analysis were also performed. Online tools ESTIMATE, MCPcounter and CIBERSORT were used to determine the stromal and immune scores of transcriptome datasets. Results: SMAD4 mutation rate was significantly lower in PASCs (0/12, 0%) than PDACs (19/70, 27.1%) while CC2D2A mutation was prevalent in PASCs (2/7, 16.67%) with none in PDACs (0/70, 0%). 869 significant DEGs(log2 Fold Change>2, false discovery rate (FDR)<0.05) were identified, including 583 down-regulated genes and 286 up-regulated genes in PASCs. DEGs were enriched in pathway of maturity onset of diabetes of the young, GO terms of epidermis development, cornification and skin development. TME analysis showed that the proportions of resting and activated NK cells, and neutrophils were significantly higher in PDACs than PASCs. Conclusions: There are genomic and TME differences between PASCs and PDACs which can possibly contribute to the clinical differences. 

Comprehensive Bioinformatical Analysis Identifies Heterogeneity of Genomics and Tumor Microenvironment Between Pancreatic Adenosquamous Carcinoma and Pancreatic Ductal Adenocarcinoma

Introduction: The tumor microenvironment is one of the significant factors contributing to the progression of pancreatic neuroendocrine tumors (panNETs). However, the underlying mechanism of how the tumor microenvironment impacts the prognosis of panNETs is not completely clear. 

Prognostic Implication of Tumor Immune Microenvironment for Pancreatic Neuroendocrine Tumors: A Bioinformatical Approach

OBJECTIVE
To assess the effect of early abdominal puncture drainage (APD) on autophagy and Nrf-2/HO-1 pathway in rats with severe acute pancreatitis (SAP) and explore the possibile mechanism.


METHODS
Thirty-two male SD rats were randomly divided into sham-operated (SO) group, SAP group with retrograde injection of 4% sodium taurocholate, APD group with insertion of a drainage tube into the lower right abdomen after SAP induction, and APD + ZnPP group with intraperitoneal injection of 30 mg/kg ZnPP 12 h before APD modeling. Blood samples were collected from the rats 12 h after modeling for analysis of amylase and lipase levels and serum inflammatory factors. The pathological changes of the pancreatic tissue were observed with HE staining. Oxidative stress in the pancreatic tissue was detected with colorimetry, and sub-organelle structure and autophagy in pancreatic acinar cells were observed by transmission electron microscopy. The expressions of autophagy-related proteins and Nrf-2/HO-1 pathway were detected using RT-PCR and Western blotting.


RESULTS
Compared with those in SAP group, the rats with APD treatment showed significantly alleviated pathologies in the pancreas, reduced serum levels of lipase, amylase and inflammatory factors, lowered levels of oxidative stress, and activated expressions of Nrf-2/HO-1 pathway in the pancreas. The ameliorating effect of ADP was significantly inhibited by ZnPP treatment before modeling. APD obviously reversed mitochondrial and endoplasmic reticulum damages and p62 accumulation induced by SAP.


CONCLUSION
APD treatment can suppress oxidative stress and repair impaired autophagy in rats with SAP by activating the Nrf-2/HO-1 pathway, thereby reducing the severity of SAP.

[Abdominal puncture drainage alleviates severe acute pancreatitis in rats by activating Nrf-2/HO-1 pathway and promoting autophagy].

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Comprehensive Bioinformatical Analysis Identifies Heterogeneity of Genomics and Tumor Microenvironment Between Pancreatic Adenosquamous Carcinoma and Pancreatic Ductal Adenocarcinoma

Prognostic Implication of Tumor Immune Microenvironment for Pancreatic Neuroendocrine Tumors: A Bioinformatical Approach

[Abdominal puncture drainage alleviates severe acute pancreatitis in rats by activating Nrf-2/HO-1 pathway and promoting autophagy].