Cancer Stem Cell Transcriptome Landscape Reveals Biomarkers Driving Breast Cancer Heterogeneity

BackgroundBreast cancers are heterogeneous diseases with distinct clinical outcomes and cancer stem cell percentages. Exploring breast cancer stem cell landscape could help understand the heterogeneity of such cancers with profound clinical relevance.MethodsWe conducted transcriptional profiling of cancer stem cells and non-cancer stem cells isolated from 3 triple negative breast cancer cell lines, analyzed the cancer stem cell transcriptome landscape that drives breast cancer heterogeneity through differential expressed gene analysis, gene ontology and pathway enrichment as well as network construction, and performed experimental validations on the network hub gene.ResultsWe identified a cancer stem cell feature panel consisting of 122 and 381 over-represented and under-expressed genes capable of differentiating breast cancer subtypes. We also underpin the prominent roles of the PI3K-AKT pathway in empowering cancer cells with uncontrolled proliferative and migrative abilities that ultimately foster cancer stemness, and reveal the potential promotive roles of ATP6V1B1 on breast tumor stemness through functional in vitro studies. ConclusionsOur study contributes in identifying a cancer stem cell feature panel for breast tumors that drives breast cancer heterogeneity at the transcriptional level, which provides a reservoir for diagnostic marker and/or therapeutic target identification once experimentally validated as demonstrated by ATP6V1B1.

Clinical features and diagnostic imaging of cholangiolocellular carcinoma compared with other primary liver cancers: a surgical perspective

Background and Objectives: Although cholangiolocellular carcinoma is considered a combined hepatocellular and cholangiocarcinoma, we feel that this classification is not appropriate. Therefore, we compared the diagnostic imaging findings, surgical prognosis, and pathological features of cholangiolocellular carcinoma with those of other combined hepatocellular and cholangiocarcinoma subtypes, hepatocellular carcinoma, and cholangiocarcinoma. Methods: The study patients included 7 with classical type combined hepatocellular and cholangiocarcinoma; 8 with stem cell feature, intermediate type combined hepatocellular and cholangiocarcinoma; 13 with cholangiolocellular carcinoma; 58 with cholangiocarcinoma; and 359 with hepatocellular carcinoma. All patients underwent hepatectomy or living-related donor liver transplantation from 2001 to 2014. Results: cholangiolocellular carcinoma could be distinguished from hepatocellular carcinom, other combined hepatocellular and cholangiocarcinoma subtypes, and cholangiocarcinoma by the presence of intratumoral Glisson’s pedicle, hepatic vein penetration, and tumor-staining pattern on angiography-assisted CT. Cholangiolocellular carcinoma was associated with a significantly lower SUV-max than that of cholangiocarcinoma on FDG-PET. Hepatocellular carcinoma, classical type, and cholangiolocellular carcinoma had significantly better prognoses than stem cell feature, intermediate type and cholangiocarcinoma. A cholangiocarcinoma component was detected in cholangiolocellular carcinoma that progressed to the hepatic hilum, and the cholangiocarcinoma component was found in perineural invasion and lymph node metastases. Conclusions: From the viewpoint of surgeon, cholangiolocellular carcinoma should be classified as a good-prognosis subtype of biliary tract carcinoma because of its tendency to differentiate into cholangiocarcinoma during its progression, and its distinctive imaging and few recurrence rates different from other combined hepatocellular and cholangiocarcinoma subtypes.