Elevated serum TGs are related to a worse prognosis of AP.

Primary liver cancer (PLC) may be mainly classified as the following four types: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatoblastoma (HB), and combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (cHCC-ICC). The majority of PLC develops in the background of tumor microenvironment, such as inflammatory microenvironments caused by viral hepatitis, alcoholic or nonalcoholic steatohepatitis, carbon tetrachloride (CCl4), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and necroptosis-associated hepatic cytokine microenvironment caused by necroptosis of hepatocytes. However, the impact of different types of microenvironments on the phenotypes of PLC generated by distinct oncogenes is still unclear. In addition, the cell origin of different liver cancers have not been clarified, as far as we know. Recent researches show that mature hepatocytes retain phenotypic plasticity to differentiate into cholangiocytes. More importantly, our results initially demonstrated that HCC, ICC, and cHCC-ICC could originate from mature hepatocytes rather than liver progenitor cells (LPCs), hepatic stellate cells (HSCs) and cholangiocytes in AKT-driven, AKT/NICD-driven and AKT/CAT-driven mouse PLC models respectively by using hydrodynamic transfection methodology. Therefore, liver tumors originated from mature hepatocytes embody a wide spectrum of phenotypes from HCC to CC, possibly including cHCC-ICC and HB. However, the underlying mechanism determining the cancer phenotype of liver tumors has yet to be delineated. In this review, we will provide a summary of the possible mechanisms for directing the cancer phenotype of liver tumors (i.e., ICC, HCC, and cHCC-ICC) in terms of oncogenic driver genes and tumor microenvironment. Moreover, this study initially revealed the cell origin of different types of liver cancer.

Background : Metastasis is the major reason for high recurrence rates and poor survival among patients with colorectal cancer (CRC). However, the underlying molecular mechanism of CRC metastasis is unclear. This study aimed to investigate the role of forkhead box K2 (FOXK2), one of the most markedly increased FOX genes in CRC, and the mechanism by which it is deregulated in CRC metastasis. Methods : FOXK2 levels were analyzed in two independent human CRC cohorts (cohort I, n = 363; cohort II, n = 390). In vitro Transwell assays and in vivo lung and liver metastasis models were used to examine CRC cell migration, invasion and metastasis. Chromatin immunoprecipitation and luciferase reporter assays were used to measure the binding of transcription factors to the promoters of FOXK2, zinc finger E-box binding homeobox 1 (ZEB1) and epidermal growth factor receptor (EGFR). Cetuximab was utilized to treat FOXK2-mediated metastatic CRC. Results : FOXK2 was significantly upregulated in human CRC tissues, was correlated with more aggressive features and indicated a poor prognosis. FOXK2 overexpression promoted CRC migration, invasion and metastasis, while FOXK2 downregulation had the opposite effects. ZEB1 and EGFR were determined to be direct transcriptional targets of FOXK2 and were essential for FOXK2-mediated CRC metastasis. Moreover, activation of EGFR signaling by EGF enhanced FOXK2 expression via the extracellular regulated protein kinase (ERK) and nuclear factor (NF)-κB pathways. The EGFR monoclonal antibody cetuximab significantly inhibited FOXK2-promoted CRC metastasis. In clinical CRC tissues, FOXK2 expression was positively correlated with the expression of p65, ZEB1 and EGFR. CRC patients who coexpressed p65/FOXK2, FOXK2/ZEB1 and FOXK2/EGFR had poorer prognosis. Conclusions : FOXK2 serves as a prognostic biomarker in CRC. Cetuximab can block the EGF-NF-κB-FOXK2-EGFR feedback loop and suppress CRC metastasis.

Chromoendoscopy seems to have a high diagnostic efficacy and improve the detection of EGC and PGLs compared with standard white light endoscopy.