Characterization of anoikis-based molecular heterogeneity in pancreatic cancer and pancreatic neuroendocrine tumor and its association with tumor immune microenvironment and metabolic remodeling.

Background: Accumulating evidence suggests that anoikis plays a crucial role in the onset and progression of pancreatic cancer (PC) and pancreatic neuroendocrine tumors (PNETs); nevertheless, the prognostic value and molecular characteristics of anoikis in cancers are yet to be determined. Materials and methods: We gathered and collated the multi-omics data of several human malignancies using the TCGA pan-cancer cohorts. We thoroughly investigated the genomics and transcriptomics features of anoikis in pan-cancer. We then categorized a total of 930 patients with PC and 226 patients with PNETs into distinct clusters based on the anoikis scores computed through single-sample gene set enrichment analysis. We then delved deeper into the variations in drug sensitivity and immunological microenvironment between the various clusters. We constructed and validated a prognostic model founded on anoikis-related genes (ARGs). Finally, we conducted PCR experiments to explore and verify the expression levels of the model genes. Results: Initially, we identified 40 differentially expressed anoikis-related genes (DE-ARGs) between pancreatic cancer (PC) and adjacent normal tissues based on the TCGA, GSE28735, and GSE62452 datasets. We systematically explored the pan-cancer landscape of DE-ARGs. Most DE-ARGs also displayed differential expression trends in various tumors, which were strongly linked to favorable or unfavorable prognoses of patients with cancer, especially PC. Cluster analysis successfully identified three anoikis-associated subtypes for PC patients and two anoikis-associated subtypes for PNETs patients. The C1 subtype of PC patients showed a higher anoikis score, poorer prognosis, elevated expression of oncogenes, and lower level of immune cell infiltration, whereas the C2 subtype of PC patients had the exact opposite characteristics. We developed and validated a novel and accurate prognostic model for PC patients based on the expression traits of 13 DE-ARGs. In both training and test cohorts, the low-risk subpopulations had significantly longer overall survival than the high-risk subpopulations. Dysregulation of the tumor immune microenvironment could be responsible for the differences in clinical outcomes between low- and high-risk groups. Conclusions: These findings provide fresh insights into the significance of anoikis in PC and PNETs. The identification of subtypes and construction of models have accelerated the progress of precision oncology.

Determination and characterization of molecular heterogeneity and precision medicine strategies of patients with pancreatic cancer and pancreatic neuroendocrine tumor based on oxidative stress and mitochondrial dysfunction-related genes.

Background: Mitochondria are significant both for cellular energy production and reactive oxygen/nitrogen species formation. However, the significant functions of mitochondrial genes related to oxidative stress (MTGs-OS) in pancreatic cancer (PC) and pancreatic neuroendocrine tumor (PNET) are yet to be investigated integrally. Therefore, in pan-cancer, particularly PC and PNET, a thorough assessment of the MTGs-OS is required. Methods: Expression patterns, prognostic significance, mutation data, methylation rates, and pathway-regulation interactions were studied to comprehensively elucidate the involvement of MTGs-OS in pan-cancer. Next, we separated the 930 PC and 226 PNET patients into 3 clusters according to MTGs-OS expression and MTGs-OS scores. LASSO regression analysis was utilized to construct a novel prognostic model for PC. qRT-PCR(Quantitative real-time PCR) experiments were performed to verify the expression levels of model genes. Results: The subtype associated with the poorest prognosis and lowerest MTGs-OS scores was Cluster 3, which could demonstrate the vital function of MTGs-OS for the pathophysiological processes of PC. The three clusters displayed distinct variations in the expression of conventional cancer-associated genes and the infiltration of immune cells. Similar molecular heterogeneity was observed in patients with PNET. PNET patients with S1 and S2 subtypes also showed distinct MTGs-OS scores. Given the important function of MTGs-OS in PC, a novel and robust MTGs-related prognostic signature (MTGs-RPS) was established and identified for predicting clinical outcomes for PC accurately. Patients with PC were separated into the training, internal validation, and external validation datasets at random; the expression profile of MTGs-OS was used to classify patients into high-risk (poor prognosis) or low-risk (good prognosis) categories. The variations in the tumor immune microenvironment may account for the better prognoses observed in high-risk individuals relative to low-risk ones. Conclusions: Overall, our study for the first time identified and validated eleven MTGs-OS remarkably linked to the progression of PC and PNET, and elaborated the biological function and prognostic value of MTGs-OS. Most importantly, we established a novel protocol for the prognostic evaluation and individualized treatment for patients with PC.

Fluoroscopic Stenting as a Bridge to Surgery versus Emergency Management for Malignant Obstruction of the Colon.

AIM: To investigate the feasibility of a SEMS (self-expandable metallic stent) as a bridge to surgery for malignant colonic obstruction. METHODS: We retrospectively reviewed 83 patients that were in accordance with inclusion criteria; of these, 33 patients that underwent fluoroscopy-guided SEMS placement followed by elective curative resection were classified as a SEMS group and 50 patients, who received emergency surgery (ES), were classified as an ES group. The clinicopathological characteristics, surgery-related parameters, complications, and three-year survival rate were compared between the two groups. RESULTS: No significant differences between the two groups were observed in any of the clinicopathologic characteristics except for higher preoperative absolute neutrophil count in the ES group (P < 0.001). Compared to the ES group, the SEMS group has significantly more cases, which featured a laparoscopic approach (72.7% vs. 14.0%, P < 0.001), lower overall stoma rate (0% vs. 34.0%, P < 0.001), and lower overall postoperative morbidity (27.3% vs. 56.0%, P=0.010). The oncological outcomes did not differ significantly between the two groups in terms of three-year overall survival (P=0.125). The technical and clinical success rates of stent placement were 91.7% and 100%, respectively. CONCLUSION: Patients treated with the stent-surgery approach had significant short-term superiorities and similar long-term outcomes, compared to patients who had emergency surgery alone. The SEMS is, therefore, safe and feasible as a bridge to surgery for malignant colonic obstruction.