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Liver metastasis stands as the primary contributor to mortality among patients diagnosed with colorectal cancer (CRC). Neutrophil extracellular traps (NETs) emerge as pivotal players in the progression and metastasis of cancer, showcasing promise as prognostic biomarkers. Our objective is to formulate a predictive model grounded in genes associated with neutrophil extracellular traps and identify novel therapeutic targets for combating CRLM. We sourced gene expression profiles from the Gene Expression Omnibus (GEO) database. Neutrophil extracellular trap-related gene set was obtained from relevant literature and cross-referenced with the GEO datasets. Differentially expressed genes (DEGs) were identified through screening via the least absolute shrinkage and selection operator regression and random forest modeling, leading to the establishment of a nomogram and subtype analysis. Subsequently, a thorough analysis of the characteristic gene CYP4F3 was undertaken, and our findings were corroborated through immunohistochemical staining. We identified seven DEGs (ATG7, CTSG, CYP4F3, F3, IL1B, PDE4B, and TNF) and established nomograms for the occurrence and prognosis of CRLM. CYP4F3 is highly expressed in CRC and colorectal liver metastasis (CRLM), exhibiting a negative correlation with CRLM prognosis. It may serve as a potential therapeutic target for CRLM. A novel prognostic signature related to NETs has been developed, with CYP4F3 identified as a risk factor and potential target for CRLM. [ABSTRACT FROM AUTHOR]

The differences between Bismuth IIIa and IIIb types of hilar cholangiocarcinoma are unclear. Thus, this study aimed to compare the clinical characteristics of the Bismuth IIIa and IIIb types of hilar cholangiocarcinoma. A case series analysis was designed to explore the clinical and pathological findings and survival of 144 patients with hilar cholangiocarcinoma who underwent curative hepatectomy between 2007 and 2018. The patients in the IIIa group received portal vein embolization and transfusion more frequently than those in the IIIb group (18.3% vs. 0.0%, P < 0.05 and 36.6% vs. 25.0%, P < 0.05). The incidence of posthepatectomy liver failure and serious surgical complications (≥ grade B) was significantly higher in the IIIa group than in the IIIb group (12.2% vs. 4.5%, P < 0.01 and 32.9% vs. 9.1%, P < 0.01). Tumors of the patients in the IIIa group had more advanced T and N stages than those of the patients in the IIIb group (P < 0.01). The patients in the IIIa group had poorer disease-free and overall survival rates than those in the IIIb group (P = 0.014 and P = 0.048). N stage and lymphovascular invasion were independently correlated with disease-free survival, whereas T and N stages were independently correlated with overall survival in the IIIb group. Meanwhile, T stage, N stage, and lymphovascular invasion were independently correlated with disease-free survival, whereas posthepatectomy liver failure, complication, and T stage were independently correlated with overall survival in the IIIa group. Hepatic and portal vessel metastasis occurred more frequently in the IIIa group than in the IIIb group (7.3% vs. 0.0%, P < 0.05). In our centers, patients with Bismuth IIIb hilar cholangiocarcinoma exhibited better disease-free and overall survival rates with more favorable clinicopathological characteristics than those with IIIa hilar cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) is a transcription factor that activates the transcription of TNF-α and regulates the inflammatory response. LITAF has been found to have potential anti-cancer effects of in several tumors. However, the role of LITAF in colorectal cancer (CRC) remains unclear. Through a comprehensive pan-cancer analysis of the Cancer Genome Atlas (TCGA), LITAF was identified as a differentially downregulated gene in CRC. We hypothesized that LITAF may participate in the modulation of CRC progression. The present study was aimed to investigate the expression profile of LITAF in CRC and its effect on metastatic behavior and stemness as well as the underlying molecular mechanism. The expression profile of LITAF in CRC, and its relationship with the prognosis of CRC were explored using public databases. LITAF expression was detected by quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry. Furthermore, the effects of overexpression or knockdown of LITAF on cell proliferation, apoptosis, migration, invasion, and stemness of CRC cells were investigated in vitro. The regulatory effect of LITAF on forkhead Box O 1 (FOXO1)-sirtuin 1 (SIRT1) signaling axis was also explored. In addition, a xenograft mouse model was used to investigate the in-vivo role of LITAF. LITAF was downregulated in tumor tissues and its expression was associated with the prognosis, pathological stage and liver metastasis. In-vitro experiments confirmed that LITAF inhibited tumor cell proliferation, migration, invasion and stemness, and induced cell apoptosis. In vivo experiments demonstrated that LITAF inhibited the tumorigenicity and liver metastasis in tumor-bearing mice. Additionally, LITAF promoted FOXO1-mediated SIRT1 inhibition, thus regulating cancer stemness and malignant phenotypes. LITAF was silenced in CRC and it participated in the progression of CRC by inhibiting CRC cell stemness, and malignant phenotypes. Therefore, LITAF may serve as a novel biomarker of CRC prognosis. [ABSTRACT FROM AUTHOR]

Heme oxygenase-1 has been identified to protect allograft from ischemia/reperfusion and immunologic rejection. Activity of heme oxygenase-1 is regulated by a guanine-thymine dinucleotide length polymorphism in the heme oxygenase-1 gene promoter. In this study, we aimed to explore the impact of the heme oxygenase-1 gene promoter polymorphism of donors and recipients on the orthotopic liver graft function after transplantation. Sixty recipients and their accompanying donors of orthotopic liver allografts were included retrospectively in this study. Heme oxygenase-1 gene promoter polymorphism was assessed using genomic DNA isolated from cryopreserved splenocytes or peripheral blood mononuclear cells and analyzed by genetic analyzer. Small allele of the donor heme oxygenase-1 gene polymorphism significantly prolonged the graft survival ( p = 0.017). Recipients of allografts from a class of small-allele carrier had significantly lower serum total bilirubin compared with recipients of a nonclass small-allele donor liver ( p < 0.01). Additionally, in recipients of small-carrier allografts, cold ischemia time (<10 h or ≥10 h) did not affect the total bilirubin significantly. Our study suggested a protective function of donor-derived heme oxygenase-1 gene promoter polymorphism on orthotopic liver allograft function after transplantation. [ABSTRACT FROM AUTHOR]