Lung adenocarcinoma (LUAD) is the main component of non-small-cell lung cancer (NSCLC) and causes a great health concern globally. The top priority of LUAD treatment is to deal with gefitinib resistance. Long non-coding RNAs are certified to modify gefitinib resistance in the course of tumor aggravation. The study focuses on addressing the function of small nucleolar RNA host gene 15 (SNHG15) on modifying gefitinib resistance in LUAD. Previously, NOTCH pathway is implicated in LUAD chemo-resistance. SNHG15 level was boosted following the depletion of NOTCH-1 in A549/GR and H1975/GR cells. Functional studies indicated that SNHG15 and multidrug resistance protein 1 (MDR-1) were overexpressed and possess tumor-promoting functions in gefitinib-resistant LUAD cells while miR-451 was downregulated and possess tumor-suppressive behaviors in gefitinib-resistant LUAD cells. Mechanically, the SNHG15 was cytoplasmically distributed in GR LUAD cells. In addition, SNHG15 released MDR-1 from the suppression of miR-451, leading to MDR-1 promotion. In addition, the elevation of SNHG15 could be attributed to ZEB1. Rescue assays highlighted that downstream molecules MDR-1 and miR-451 could reverse the effects of SNHG15 downregulation on gefitinib-resistant LUAD cells. SNHG15 could alter chemo-resistance of LUAD cells to Gefitinib via regulating miR-451/MDR-1, which could be inspiring findings for the advancement of chemo-therapies for LUAD.

Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1β has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of HNF-1β promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1β in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1β indicated poor prognosis. We overexpressed HNF-1β in liver cancer cell lines and found the expression of liver progenitor cell markers and stemness were upregulated. The invasion ability and epithelial-mesenchymal transition (EMT)-associated genes were also significantly higher in liver cancer cells overexpressing HNF-1β than in the control group. A mechanistic study suggested the activation of the Notch signalling pathway probably plays a key role downstream of HNF-1β. More importantly, HNF-1β promoted tumourigenesis of HCC cells in vivo. In conclusion, high expression of HNF-1β not only promoted the de-differentiation of HCC cells into liver cancer stem cells through activating the Notch pathway but also enhanced the invasive potential of HCC cells and EMT occurrence, which would contribute to the enhancement of cell migration and invasion.

Normally, hepatic progenitor cells (HPCs) are activated and differentiate into hepatocytes or bile ductular cells to repair liver damage during liver injury. However, it remains controversial whether the abnormal differentiation of HPCs occurs under abnormal conditions. Lipopolysaccharide (LPS), a component of the microenvironment, promotes liver fibrosis. In the present study, HPCs promoted liver fibrosis in rats following carbon tetrachloride (CCl) treatment. Meanwhile, the LPS level in the portal vein was elevated and played a primary role in the fate of HPCs. In vitro, LPS inhibited the hepatobiliary differentiation of HPCs. Concurrently, HPCs co-cultured with LPS for 2 weeks showed a tendency to differentiate into myofibroblasts (MFs). Thus, we conclude that LPS promotes the aberrant differentiation of HPCs into MFs as a third type of descendant. This study provides insight into a novel differentiation fate of HPCs in their microenvironment, and could thus lead to the development of HPCs for treatment methods in liver fibrosis.

e16070 Background: The data about prognosis difference of patients with pT2 stage gastric cancer (GC) after radical surgery is diverse. The latest TNM staging system does not define details for the pT2 stage subclassification. The purpose of this study is to investigate the survival difference according to depth of tumor muscularis propria involvement and find biomarker to reinforce the prognostic and therapy-guided ability of TNM staging system. Methods: A total of 380 patients with pT2 GC after radical surgery were retrospectively analyzed, including 185 in sMP (superficial muscularis propria) group and 195 in dMP (deep muscularis propria) group. The log-rank test was used to identify survival outcomes. Independent factors were identified by multivariable Cox proportional hazard model for OS. Results: The overall survival (OS) of patients in sMP group was significantly better than patients in dMP group (P = 0.007). On multivariate analysis, age (＜60 vs ≥60: P = 0.004, HR, 2.075(95%CI: 1.261-3.414)), primary location (P = 0.002, U vs M: 0.985(0.509-1.909); U vs L: 0.400(0.235-0.680)), depth of tumor invasion (sMP vs dMP: P = 0.050, 1.584(1.261-3.414), pN stage (P = 0.000, N0 vs N1: 2.304(1.364-3.890); N0 vs N2: 1.879(0.967-3.652); N0 vs N3: 5.335(2.533-11.237)), expression of p53 (negative vs positive: P = 0.016, 1.793(1.117-2.879)) were independent prognostic factors for the OS. In pN0 stage tumor, the sMP group had a significantly better OS than the dMP group (P = 0.014). When classified as N+, there was no obviously difference of OS between two groups (P = 0.384). When patients were stratified according to the depth of tumor invasion and pN stage, the OS was not significant difference between dMPN0 group and sMPN1-2 group (P = 0.100), the OS of patients with adjuvant chemotherapy were statistically better than those without in dMPN0 group (P = 0.045), but not significance in sMPN1-2 group (P = 0.486). After further grouping according to adjuvant chemotherapy status, in comparison to sMPN1-2 patients, dMPN0 patients with adjuvant chemotherapy had better OS (P = 0.015), but not significance in patients without (P = 0.599). Upon stratification according to the expression of p53, in p53-positive group, greater OS could be observed in patients with sMPN0 than patients with dMPN0 (P = 0.002). Similar OS could be seen between dMPN0 patients with p53-positive and T2N1-2 patients (P = 0.872). Conclusions: For pT2 gastric cancer patients, there were differences in survival outcomes for sMP and dMP invasion. The prognosis of dMPN0 patients were similar to patients with sMPN1-2, and dMPN0 patients who accepted adjuvant chemotherapy had an improved prognosis than those without. Appropriate adjuvant chemotherapy should be considered for patients with dMPN0 stage. In addition, positive expression of p53 could be potential factors to identify the different prognoses for patients with pT2 gastric cancers.