Comprehensive landscape of the IPAF inflammasomes in pan-cancer: A bulk omics research and single-cell sequencing validation.

BACKGROUND: IPAF (ICE-protease Activating Factor) is a nucleotide-binding/leucine-rich repeat (NLR) protein known as the cysteine-associated recruitment domain 12 (CARD12). Previous studies only discuss the role of IPAF inflammasomes in specific tumors. The role of IPAF inflammasomes in pan-cancer is still unclear. Therefore, we performed a comprehensive analysis of IPAF inflammasome in 33 tumors. METHODS: We used databases like The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) from the UCSC XENA (http://xena.ucsc.edu/) to retrieve and analyze gene expression. The influence of IPAF inflammasome on the prognosis of tumor patients was analyzed using univariate Cox regression analysis and Kaplan-Meier survival analysis. Furthermore, we conducted the following analysis: Single-sample gene set enrichment analysis, single-cell level functional state analysis, single-cell sequencing, immune cell infiltration analysis, and tumor immune dysfunction and exclusion (TIDE) score. RESULTS: First, the differential expression of IPAF inflammasome-related genes (IPAF-RGs) in 33 tumors were analyzed. The results revealed that IPAF-RGs were significantly and differentially expressed in eight tumors. The prognostic significance of IPAF inflammasome scores was different in different tumors. A positive correlation was observed between IPAF inflammasomes scores and CD8+ T cells in most tumors. Further analysis revealed that IPAF inflammasome might affect tumor immunity mainly by mediating effector T cell recruitment via the expression of chemokines such as CXCL9, CXCL10, and CCL5. The analysis of TIDE and IPAF inflammasome scores revealed a significant negative correlation between IPAF inflammasome and TIDE scores in 11 tumors. CONCLUSION: A pan-cancer analysis of IPAF inflammasome in various tumors was performed. The results highlight the potential value of IPAF inflammasome in response to immunotherapy in patients and provide a new direction for future immunotherapy.

Propensity score-matched comparison between totally laparoscopic right hemicolectomy with transcolonic natural orifice specimen extraction and conventional laparoscopic surgery with mini-laparotomy in the treatment of ascending colon cancer (with video).

BACKGROUND AND AIMS: Now that the debate about the safety and effectiveness of laparoscopic versus open surgery is over, attention has turned to innovations that can verify whether minimizing the impact of laparoscopy on the abdominal wall can further reduce pain, improve patient comfort, lead to superior cosmesis, and reduce morbidity. The aim of this study was to further explore the application value of totally laparoscopic right hemicolectomy with transcolonic natural orifice specimen extraction (NOSE) and to evaluate the short-term efficacy of transcolonic NOSE surgery for resecting specimens of ascending colon cancer. METHODS: From January 2016 to May 2017, a retrospective study was conducted in Guangxi. Propensity score matching was used to minimize the bias from nonrandomized treatment assignment. Patients were followed up through May 2020. RESULTS: Forty-nine patients underwent totally laparoscopic right hemicolectomy with transcolonic NOSE and 116 patients laparoscopic right hemicolectomy with mini-laparotomy (ML) procedures at our institution. After propensity score matching, each group included 45 patients, and all covariate imbalances were alleviated. The transcolonic NOSE group and the ML group did not differ significantly in terms of baseline clinical characteristics. The transcolonic NOSE group was associated with a shorter time to first flatus (NOSE vs ML: 1.8 ± .5 vs 3.2 ± .8, P = .032), a shorter length of hospital stay (11.3 ± 2.5 days vs 13.0 ± 3.1 days, P = .034), a shorter time to first liquid intake (2.6 ± .8 vs 3.8 ± .9, P = .068), less pain (1.8 ± .8 vs 4.2 ± .7, P = .013), less analgesia requirement (6 [13.3%] vs 21 [46.7%], P = .001), and lower C-reactive protein levels on postoperative day 1 (3.6 ± 1.7 vs 8.2 ± 2.2, P = .001) and postoperative day 3 (NOSE 2.4 ± 1.4 vs M: 4.6 ± 1.7 [P = .013]) than the ML group. The median follow-up was 28.4 months (interquartile range, 18.0-36.0). The 3-year overall survival rates were similar between the transcolonic NOSE group and the ML group. CONCLUSIONS: In total, laparoscopic right hemicolectomy with transcolonic specimen extraction appears to be safe for selected patients with ascending colon cancer as a minimally invasive surgery.

Siva­1 regulates multidrug resistance of gastric cancer by targeting MDR1 and MRP1 via the NF­κB pathway.

Siva­1 is a well­known anti­apoptosis protein that serves a role in multiple types of cancer cells. However, whether Siva­1 affects multidrug resistance via the NF­κB pathway in gastric cancer is currently unknown. The present study aimed to determine the possible involvement of Siva­1 in gastric cancer anticancer drug resistance in vitro. A vincristine (VCR)­resistant KATO III/VCR gastric cancer cell line with stable Siva­1 overexpression was established. The protein expression levels of Siva­1, NF­κB, multidrug resistance 1 (MDR1) and multidrug resistance protein 1 (MRP1) were detected via western blotting. The effect of Siva­1 overexpression on anticancer drug resistance was assessed by measuring the 50% inhibitory concentration of KATO III/VCR cells to VCR, 5­fluorouracil and doxorubicin. The rate of doxorubicin efflux and apoptosis were detected by flow cytometry. Additionally, colony formation, wound healing and Transwell assays were used to detect the proliferation, migration and invasion of cells, respectively. The results of the current study revealed that the Siva­1­overexpressed KATO III/VCR gastric cancer cells exhibited a significantly decreased sensitivity to VCR, 5­fluorouracil and doxorubicin. The results of flow cytometry revealed that the percentage of apoptotic cells decreased following overexpression of Siva­1. The colony formation assay demonstrated that cell growth and proliferation were significantly promoted by Siva­1 overexpression. Additionally, Siva­1 overexpression increased the migration and invasion of KATO III/VCR cells in vitro. Western blot analysis determined that Siva­1 overexpression increased NF­κB, MDR1 and MRP1 levels. The current study demonstrated that overexpression of Siva­1, which functions as a regulator of MDR1 and MRP1 gene expression in gastric cancer cells via promotion of NF­κB expression, inhibited the sensitivity of gastric cancer cells to certain chemotherapies. These data provided novel insight into the molecular mechanisms of gastric cancer, and may be of significance for the clinical diagnosis and therapy of patients with gastric cancer.

[Risk factors associated with anastomotic leak in patients with Crohn disease undergoing bowel resections].

OBJECTIVE: To investigate the risk factors and the prevention management of anastomotic leak in patients with Crohn disease undergoing bowel resections. METHODS: Clinical data of 91 patients with Crohn disease undergoing intestinal resection from 1990 to 2010 were analyzed retrospectively. Logistic regression analysis was used to assess the risk factors of anastomotic leak. RESULTS: A total of 120 intestinal anastomosis were performed in 91 patients, and anastomosis leak occurred in 14 patients (11.7%). Univariate analysis showed that operative timing (emergency or elective surgery), anastomosis type (side-to-side or end to end and end-to-side), operative time (≥3 h or <3 h), methods of anastomosis (handsewn or stapled) were the risk factors for anastomotic leak (P<0.05). Multivariate analysis revealed that emergency surgery (OR=3.891, 95%CI:1.332-13.692), end to end and end-to-side anastomosis (OR=3.236, 95%CI:1.165-11.950), handsewn anastomosis (OR=5.715, 95%CI:1.454-17.328) were independent risk factors of anastomotic leak. CONCLUSION: Avoiding emergency operation, use of side to side anastomosis, and application of stapling may lower the incidence of postoperative anastomotic leak in patients with Crohn disease undergoing bowel resections.