Proteomic characteristics of mesenchymal subtypes of hepatocellular carcinoma
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ABSTRACT:
PROVIDER: PRJNA818645 | ENA |
REPOSITORIES: ENA
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Project description:Clinical heterogeneity of hepatocellular carcinoma (HCC) reflected in unequal outcome of treatment is poorly defined in molecular level, and molecular subtypes and their associated biomarkers have not been established to improve prognostification and treatment of HCC. Using reverse phase protein arrays (RPPA) technologies, we analyzed protein expression profiling data from HCC patients, uncovered mesenchymal subtype, and identified gene expression signature associated with mesenchymal phenotype of HCC.
2024-01-01 | GSE199141 | GEO
Project description:Mesenchymal subtypes of hepatocellular carcinoma
| PRJNA555598 | ENA
Project description:Clinical heterogeneity of hepatocellular carcinoma (HCC) reflected in unequal outcome of treatment is poorly defined in molecular level, and molecular subtypes and their associated biomarkers have not been established to improve prognostification and treatment of HCC. Using microarray technologies, we analyzed gene expression profiling data from HCC patients, uncovered mesenchymal subtype, and identified gene expression signature associated with mesenchymal phenotype of HCC.
2020-07-01 | GSE134568 | GEO
Project description:Previously, we have found a specific subtype of HCCs named solitary large hepatocellular carcinoma (SLHCC), which was >5 cm in diameter, had just single lesion, and always grew expansively within an intact capsule or pseudocapsule. Accordingly, we classified HCCs into 3 different subtypes: SLHCC, nodular HCC (NHCC, node number ≥ 2) and small HCC (SHCC, solitary nodular, diameter ≤ 5 cm). Further study confirmed that SLHCC had unique clinical and pathological characteristics, and its metastatic potential was comparable with SHCC, but significantly lower than NHCC. After hepatic resection, SLHCC exhibited a similar long-term overall and disease-free survival with SHCC, but much better than NHCC. To gain a better understanding of the molecular biologic characteristics of SLHCC, we performed miRNAs array analysis in there three subtypes of HCC.
2015-05-01 | E-MTAB-3347 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is a common malignancy with high mortality due to a lack of effective therapies. HCC represents a collection of highly heterogeneous tumor types but a general molecular classification of HCC is lacking. Here, we define three molecular subtypes of HCC that are observed across various independent patient cohorts and profiling platforms. Analysis of the expression signatures indicates that a limited number of pathways and processes drive the clustering of these subtypes. Notably, TGF-beta signaling is a critical factor that distinguishes two subtypes of high-grade tumors, and is associated with early tumor recurrence. Furthermore, both bioinformatics and functional analyses reveal molecular crosstalk between TGF-beta and WNT signaling pathways. These findings suggest that TGF-beta plays a critical role in a subclass of HCC tumors and may enhance WNT pathway activation in the absence of activating mutations in canonical pathway components. This study is an example of how robust molecular subclassification can be used to interrogate molecular abnormalities in the context of human cancer. Experiment Overall Design: Four hepatocellular carcinoma (HCC) cell line samples treated or untreated by TGF-beta
2009-09-17 | E-GEOD-10393 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers, the second leading cause of cancer mortality worldwide. Although HCC surgical treatment may be curative in the early stages, its five-year overall survival is only 50-70%. Advances in proteomic technologies have expanded the breadth and depth of cancer proteome characterization. Here, we present the largest characterization effort on proteomic profiling of 222 tumor and paired non-tumor tissues in clinically early HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A). Quantitative proteomic data identified three more-refined subtypes in the early- stage cohort of HCC (termed S-I, S-II and S-III) with different clinical outcomes. S-I retained hepatic detoxification and metabolic functions with the best prognosis, S-II increased molecular expression related to proliferation, and S-III showed distinct enrichment of tumor metastasis and immune response pathways and the poorest prognosis. The subtype specific signatures targeted by known FDA approved drugs or inhibitors under clinical investigations for HCC provide a novel resource for HCC therapeutic targets. A new mechanism of disrupted cholesterol homeostasis with aberrant accumulation of cholesteryl esters was also highlighted in S-III. Thus, this study represents the first proteomic stratification of early-stage HCC, providing insights into tumor biology and personalized targeted therapy.
2019-05-29 | PXD006512 | Pride
Project description:Primary outcome(s): To clarify the pathological characteristics of submucosal(SM) invasion site and number among LST subtypes.
| 2635539 | ecrin-mdr-crc
Project description:Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers, the second leading cause of cancer mortality worldwide. Although HCC surgical treatment may be curative in the early stages, its five-year overall survival is only 50-70%. Advances in proteomic technologies have expanded the breadth and depth of cancer proteome characterization. Here, we present the largest characterization effort on proteomic profiling of 222 tumor and paired non-tumor tissues in clinically early HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 and A). Quantitative proteomic data identified three more-refined subtypes in the early- stage cohort of HCC (termed S-I, S-II and S-III) with different clinical outcomes. S-I retained hepatic detoxification and metabolic functions with the best prognosis, S-II increased molecular expression related to proliferation, and S-III showed distinct enrichment of tumor metastasis and immune response pathways and the poorest prognosis. The subtype specific signatures targeted by known FDA approved drugs or inhibitors under clinical investigations for HCC provide a novel resource for HCC therapeutic targets. A new mechanism of disrupted cholesterol homeostasis with aberrant accumulation of cholesteryl esters was also highlighted in S-III. Thus, this study represents the first proteomic stratification of early-stage HCC, providing insights into tumor biology and personalized targeted therapy.
2019-03-01 | PXD008373 | Pride
Project description:Purpose: There is substantial heterogeneity within the human papillomavirus (HPV) positive head and neck cancer (HNC) tumors that predispose them to different outcomes, however this subgroup is poorly characterized due to various historical reasons. Experimental Design: we perform unsupervised gene expression clustering on well-annotated HPV(+) HNC samples from two cohorts ( 84 total primary tumors), as well as 18 HPV(-) HNCs, to discover subtypes, and begin to characterize the differences between the subtypes in terms of their HPV characteristics, pathway activity, whole-genome somatic copy number variations and mutation frequencies. Results: We identified two distinctive HPV(+) subtypes by unsupervised clustering. Membership in the HPV(+) subtypes correlates with genic viral integration status, E2/E4/E5 expression levels and the ratio of spliced to full length HPV oncogene E6. The subtypes also show differences in copy number alterations, in particular the loss of chr16q and gain of chr3q, PIK3CA mutation, and in the expression of genes involved in several biological processes related to cancer, including immune response, oxidation-reduction process, and keratinocyte and mesenchymal differentiation. Conclusion: Our characterization of two subtypes of HPV(+) tumors provides valuable molecular level information in relation to the alternative paths to tumor development and to that of HPV(-) HNCs. Together, these results will shed light on stratifications of the HPV(+) HNCs and will help to guide personalized care for HPV(+) HNC patients. 36 head and neck primary tumors (18 HPV+ and 18 HPV-) and their matched blood samples were collected and genotyped by Illumina OmniExpress SNP array. RNA-seq was also performed on the same set of tumor samples.
2016-05-13 | E-GEOD-74927 | biostudies-arrayexpress
Project description:Multiple carcinogenesis is one of the major characteristics of human hepatocellular carcinoma (HCC). The history of multiple tumors, i.e., whether they are derived from a common precancerous or cancerous ancestor or individually from hepatocytes, is a major issue. Multiple HCC is clinically classified into intratumor metastasis (IM) and multicentric carcinogenesis (MC). Molecular markers differentiating IM and MC are of interest to clinical practitioners because clinical diagnosis of IM and MC often leads to different therapies. We analyzed multiple HCCs for somatic mutations of cancer-related genes, chromosomal aberrations, and promoter methylation of tumor suppressor genes, using techniques such as high-resolution melting, array-comparative genomic hybridization (CGH), and quantitative methylation-specific PCR. Comparative genomic hybridizaion experiments. A total of 20 tumor samples: ten pairs of HCC (from ten patients).
2010-09-08 | E-GEOD-22635 | biostudies-arrayexpress