Exogenous interleukin-4 (IL-4) has been demonstrated to affect the growth of different human malignancies including pancreatic cancer cells. The aim of our study was to determine the role of endogenously expressed IL-4-receptor-α-chain (IL-4Rα) in pancreatic cancer cells. IL-4Rα-suppression was achieved by generating Capan-1 cells stably expressing shRNA targeting IL-4Rα. The malignant phenotype was characterized by assessing growth properties, directional and non-directional cell movement in vitro and tumor growth in vivo. Signaling pathways were analyzed upon IL-4 and IL-13 stimulation of wildtype (WT) and control-transfected cells compared to IL-4Rα-knockdown cells. Silencing of IL-4Rα resulted in reduced anchorage-dependent cell growth (p < 0.05) and reduced anchorage-independent colony size (p < 0.001) in vitro. Moreover, cell movement and migration was inhibited. IL-4 and IL-13 stimulation of Capan-1-WT cells induced activation of similar pathways like stimulation with Insulin-like growth factor (IGF)-I. This activation was reduced after IL-4Rα downregulation while IGF-I signaling seemed to be enhanced in knockdown-clones. Importantly, IL-4Rα silencing also significantly suppressed tumor growth in vivo. The present study indicates that endogenously expressed IL-4 and IL-4Rα contribute to the malignant phenotype of pancreatic cancer cells by activating diverse pro-oncogenic signaling pathways. Addressing these pathways may contribute to the treatment of the disease.

Objective: Colon cancer is associated with multiple levels of molecular heterogeneity. RNA processing converts primary transcriptional RNA to mature RNA, which drives tumourigenesis and its maintenance. The characterisation of RNA processing genes in colon cancer urgently needs to be elucidated. Methods: In this study, we obtained 1033 relevant samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to explore the heterogeneity of RNA processing phenotypes in colon cancer. Firstly, Unsupervised hierarchical cluster analysis detected 4 subtypes with specific clinical outcomes and biological features via analysis of 485 RNA processing genes. Next, we adopted the least absolute shrinkage and selection operator (LASSO) as well as Cox regression model with penalty to characterise RNA processing-related prognostic features. Results: An RNA processing-related prognostic risk model based on 10 genes including FXR1, MFAP1, RBM17, SAGE1, SNRPA1, SRRM4, ADAD1, DDX52, ERI1, and EXOSC7 was identified finally. A composite prognostic nomogram was constructed by combining this feature with the remaining clinical variables including TNM, age, sex, and stage. Genetic variation, pathway activation, and immune heterogeneity with risk signatures were also analysed via bioinformatics methods. The outcomes indicated that the high-risk subgroup was associated with higher genomic instability, increased proliferative and cycle characteristics, decreased tumour killer CD8 ⁺ T cells and poorer clinical prognosis than the low-risk group. Conclusion: This prognostic classifier based on RNA-edited genes facilitates stratification of colon cancer into specific subgroups according to TNM and clinical outcomes, genetic variation, pathway activation, and immune heterogeneity. It can be used for diagnosis, classification and targeted treatment strategies comparable to current standards in precision medicine. It provides a rationale for elucidation of the role of RNA editing genes and their clinical significance in colon cancer as prognostic markers.

Acute appendicitis with mesenteric vein thrombosis (MVT) is an uncommon condition and usually lacks specific clinical manifestations, which leads to a high rate of misdiagnosis or delayed diagnosis, especially when it is accompanied by other abdominal diseases. Prompt and accurate recognition is vital for treatment and prognosis. A 37-year-old woman had a history of acute metastatic right lower abdominal pain, nausea, and fever. A contrast-enhanced computed tomography (CT) scan showed a filling defect in the mesenteric vessels. The patient was diagnosed with acute appendicitis complicated by MVT and was treated with anticoagulation and intravenous antibiotics. The follow-up CT scan showed full resolution of the thrombosis and inflammation. Clinical awareness is essential for recognizing MVT, especially when it is accompanied by other common acute abdominal diseases, such as acute appendicitis. Contrast-enhanced CT is helpful for the diagnosis of MVT and is recommended for patients with acute abdominal diseases.

To investigate the expression pattern and prognostic significance of glypican-3 (GPC3) in gastric cancer (GC) and identify its potential upstream non-coding RNA regulatory network. Transcriptomic data from TCGA-STAD and GEO datasets were used to compare GPC3 expression between GC and non-tumor gastric tissues, with validation using GEPIA. The prognostic value of GPC3 was evaluated using TCGA-STAD, GEPIA, and Kaplan–Meier Plotter. An independent clinical cohort from our center was included for immunohistochemical validation, and associations between GPC3 expression and clinicopathological features were assessed using chi-square or exact tests, as appropriate. Upstream miRNAs targeting GPC3 were predicted using starBase and screened by correlation and survival analyses. Candidate lncRNAs were further identified by integrating starBase and miRNet to identify a putative non-coding RNA regulatory relationship. GPC3 was significantly upregulated in GC tissues compared with non-tumor gastric tissues in TCGA-STAD, GSE33335, GSE54129, and GEPIA. High GPC3 expression was associated with worse overall survival and progression-free survival. In the independent cohort, GPC3 protein expression was elevated in GC tissues and showed exploratory associations with advanced T stage (P < 0.001), N stage (P = 0.014), TNM stage (P = 0.013), and perineural invasion (P = 0.041). Among 15 candidate miRNAs, hsa-miR-96-5p showed the strongest negative correlation with GPC3 (r=-0.32614, P < 0.001). LINC02381 was positively correlated with GPC3 (r = 0.30255, P < 0.001), negatively correlated with hsa-miR-96-5p (r=-0.15184, P < 0.01), and its high expression was associated with poor prognosis. GPC3 is overexpressed in GC and associated with poor prognosis. Bioinformatic analyses further suggested a putative LINC02381/miR-96-5p/GPC3 regulatory relationship associated with GPC3 expression in GC.