Gene Expression Profiles Associated with A Simple and Reliable Myeloid Signature for HCC
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PROVIDER: PRJNA556811 | ENA |
REPOSITORIES: ENA
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Project description:BACKGROUND & AIMS: Despite the increasing appreciation of the roles that myeloid cells play in tumor progression and therapy, challenges remain in interpreting the balance of the tumor-associated myeloid response and its translational value. We aimed to construct a simple and reliable signature of local myeloid responses in hepatocellular carcinoma (HCC). METHODS: Using in situ immunohistochemistry (IHC), we assessed myeloid features that revealed the distribution of major myeloid subtypes in both the peri- and intratumoral regions of HCC. A signature was constructed using an L1-penalized Cox regression model based on the postsurgery recurrence data from a training subset (n = 244) that was validated in the testing subset (n = 244) and independent internal (n = 341) and external (n = 348) cohorts. Multiplexed immunofluorescence staining, flow cytometry and transcriptomic analyses were performed to examine the immunological deviations associated with the myeloid signature. Further, we built nomograms to provide a more robust and personalized prognosis for HCC patients. RESULTS: A 2-feature-based, myeloid-specific prognostic signature, namely the myeloid response score (MRS), was constructed. The increase in the MRS was associated with a change in the predominant myeloid populations from CD169+ macrophages (Mφs) in MRSlow HCCs to CD15+CD11b+ neutrophils and CD11b+CD169- Mφs in MRShigh tumors, suggesting a shift in the balance of the myeloid response from antitumor to protumor activities. This alteration was also accompanied by the enhancement of CD8+ T cell exhaustion patterns, including impaired cytotoxic potential and elevated programmed cell death protein 1 (PD-1) expression. The MRS and the MRS-based nomograms had higher accuracy for predicting recurrence and patient survival than the Barcelona Clinic Liver Cancer (BCLC) and tumor-node-metastasis (TNM) staging systems and were validated in a multicenter cohort of HCC patients. Moreover, in a separate cohort of 51 patients, we provided evidence that the MRS was associated with the efficacy of sorafenib treatment for recurrent HCC. CONCLUSIONS: We identified and validated a descriptive and prognostic myeloid signature for HCC. HCC tissues with low, intermediate, and high MRS estimates represent tumors with immunocompetent, immunodeficient, and immunosuppressive subtypes, respectively. This technically simple and reliable myeloid signature shows remarkable prognostic potential for HCC after resection and could serve as the basis for the stratification of HCC immune subtypes to aid in a wide range of clinical decisions.
2019-07-27 | GSE134921 | GEO
Project description:In this study we investigated the miRNA expression profile of Hepatocellular carcinoma (HCC) specimens from radical resection. We developed a unique 20 miRNA signature that could significantly distinguish HCC venous metastasis from metastasis-free HCC. In contrast to HCC staging systems, this signature was capable of predicting survival and recurrence of HCC patients with multinodular or solitary tumors, including those with early-stage disease. Moreover, the signature was an independent and significant predictor of patient prognosis and relapse when compared to other available clinical parameters. Our study suggests that these 20 miRNAs can enable HCC prognosis and may have clinical utility for the advance identification of HCC patients with a propensity towards metastasis/recurrence. Keywords: disease state design Gene expression profiles were conducted in primary HCC and corresponding noncancerous hepatic tissues from 244 Chinese HCC patients. A total of 134 well-defined cases were used as a training group. Among them, 30 had primary HCC lesions accompanied by tumor emboli and 104 had solitary HCC with no metastasis/recurrence found at follow-up (3 yr). We used a testing group of 110 independent cases. The testing cases included 43 multinodular and 67 solitary HCC. In addition, eight normal liver tissues from disease-free patients were included as normal controls. In the analysis of the 244 HCC cases, RNA was isolated in a pairwise fashion from tumor or non-tumor tissue and samples were selected in random order for miRNA analysis to avoid grouping bias.
2008-01-14 | E-GEOD-6857 | biostudies-arrayexpress
Project description:In this study we investigated the miRNA expression profile of Hepatocellular carcinoma (HCC) specimens from radical resection. We developed a unique 20 miRNA signature that could significantly distinguish HCC venous metastasis from metastasis-free HCC. In contrast to HCC staging systems, this signature was capable of predicting survival and recurrence of HCC patients with multinodular or solitary tumors, including those with early-stage disease. Moreover, the signature was an independent and significant predictor of patient prognosis and relapse when compared to other available clinical parameters. Our study suggests that these 20 miRNAs can enable HCC prognosis and may have clinical utility for the advance identification of HCC patients with a propensity towards metastasis/recurrence. Keywords: disease state design
2008-01-14 | GSE6857 | GEO
Project description:Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance in the steatohepatitis setting. Here, we present a high resolution atlas of hepatic innate immune cells from patients with HCC that unravels a steatohepatitis contexture characterized by influx of inflammatory and immunosuppressive myeloid cells. A discrete myeloid cell population identified by selective expression of TREM1 and CD163 expands in steatohepatitis-HCC. We refer to this population as TREM1+ regulatory myeloid cells (Mreg), as it potently suppresses T cell effector functions, highly expresses TGFB1 and IL13RA1 and localizes to HCC fibrotic lesions.
2024-02-04 | GSE245906 | GEO
Project description:Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance in the steatohepatitis setting. Here, we present a high resolution atlas of hepatic innate immune cells from patients with HCC that unravels a steatohepatitis contexture characterized by influx of inflammatory and immunosuppressive myeloid cells. A discrete myeloid cell population identified by selective expression of TREM1 and CD163 expands in steatohepatitis-HCC. We refer to this population as TREM1+ regulatory myeloid cells (Mreg), as it potently suppresses T cell effector functions, highly expresses TGFB1 and IL13RA1 and localizes to HCC fibrotic lesions.
2024-02-04 | GSE245905 | GEO
Project description:Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance in the steatohepatitis setting. Here, we present a high resolution atlas of hepatic innate immune cells from patients with HCC that unravels a steatohepatitis contexture characterized by influx of inflammatory and immunosuppressive myeloid cells. A discrete myeloid cell population identified by selective expression of TREM1 and CD163 expands in steatohepatitis-HCC. We refer to this population as TREM1+ regulatory myeloid cells (Mreg), as it potently suppresses T cell effector functions, highly expresses TGFB1 and IL13RA1 and localizes to HCC fibrotic lesions.
2024-02-04 | GSE245908 | GEO
Project description:Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and is the one of the few cancers in which a continued increase in incidence has been observed over several years. HCC associated with chronic liver disease evolves from precancerous lesion and early HCC to overt cancer, and identifying key molecules contributing to early stage HCC is an urgent need. α-Fetoprotein (AFP) is the best serum biomarker for diagnosis of HCC, but sensitivity is low, particularly in detection of early-stage HCC. Therefore, novel and reliable diagnostic biomarkers to complement AFP are needed to improve HCC diagnosis. We aim to determine transcriptome-based molecular signature of multistep hepatocarcinogenesis, and to identify novel serum biomarkers to diagnose early stage HCC patient.
2020-12-31 | GSE114564 | GEO
Project description:Although clinical features, cytogenetics, and mutations are widely used to predict prognosis in patients with acute myeloid leukemia (AML), further refinement of risk stratification is necessary for optimal treatment, especially in cytogenetically normal (CN) patients. We sought to generate a simple gene expression signature as a predictor of clinical outcome through analyzing the mRNA arrays of de novo CN-AML patients. Among 43 treatment response-related genes, expression of 11 genes was significantly associated with overall survival (OS) in univariate Cox regression analysis in 104 patients who received standard intensive chemotherapy. We integrated the z-transformed expression levels of these 11 genes to generate a risk scoring system. Higher risk scores were significantly associated with shorter OS (median 17.0 months vs. not reached, P<0.001) in ours and 3 other validation cohorts. In conclusion, we developed a simple mRNA expression signature for prognostication in CN-AML patients. This prognostic biomarker will help refine the treatment strategies for this group of patients.
2017-02-09 | GSE71014 | GEO
Project description:Hepatocellular carcinoma (HCC) is a life-threatening disease. Due to the lack of reliable diagnostic biomarkers, the diagnosis of this disease is challenging. Recently, plasma glycoproteomics has emerged as a powerful tool for the identifying disease diagnostic biomarkers. Here, we performed a comprehensive proteomic and glycoproteomic analysis in the plasma of 12 HCC patients and 12 healthy control (HC) individuals. We identified 20 signature proteins and 32 signature IGPs that can distinguish HCC from HC effectively. Moreover, we demonstrated that IGPs profiles could be better predictive biomarkers for screening HCC than protein profiles. Pathways for signature proteins and IGPs were illustrated. For the first time, we showed that the protein expression level of LGALS3BP, as well as its N-linked glycosylation at the N511/398 sites could be a valuable diagnosis biomarker of HCC. Overall, our data suggest a major role for glycoproteomics in understanding HCC, and presents a number of new biomarkers for future
2023-05-09 | PXD039745 |
Project description:Hepatocellular carcinoma (HCC) is the second leading cause of cancer death worldwide, indicating urgent need for preventive strategies. Cancer chemoprevention discovery is challenged by the absence of tractable and clinically relevant human model systems and the complex cell circuits supporting carcinogenesis. Here, we developed a simple and robust human liver cell-based system in which persistent hepatitis B/C virus infection or ethanol induce an HCC risk signature robustly predicting long-term HCC risk in cirrhotic patients. Using a computationally enriched small molecule cell-based screen followed by ex/in vivo validation in human liver tissues and animal models, we identified captopril as an HCC chemopreventive agent that antagonizes the EGF/EGFR pathway, a key driver of liver disease and hepatocarcinogenesis. Our system, modeling the cell circuits encoded in the clinical HCC risk signature, enables fast-track cancer chemoprevention discovery and provides an urgently needed approach for improving the dismal prognosis of patients at risk of HCC.
2021-06-28 | GSE81801 | GEO