Hongguang Zhu

Bio: Hongguang Zhu is an academic researcher from Fudan University. The author has contributed to research in topics: Hepatocellular carcinoma & Hepatitis B virus. The author has an hindex of 23, co-authored 56 publications receiving 2249 citations. Previous affiliations of Hongguang Zhu include Fudan University Shanghai Medical College.

Plasma MicroRNA Panel to Diagnose Hepatitis B Virus–Related Hepatocellular Carcinoma

Abstract: Purpose More than 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapy as a result of late clinical presentation and diagnosis. We aimed to identify plasma microRNAs for diagnosing hepatitis B virus (HBV) –related HCC. Patients and Methods Plasma microRNA expression was investigated with three independent cohorts including 934 participants (healthy, chronic hepatitis B, cirrhosis, and HBV-related HCC), recruited between August 2008 and June 2010. First, we used microarray to screen 723 microRNAs in 137 plasma samples for diagnosing HCC. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n 407) and then validated using an independent cohort (n 390). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results We identified a microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) that provided a high diagnostic accuracy of HCC (AUC 0.864 and 0.888 for training and validation data set, respectively). The satisfactory diagnostic performance of the microRNA panel persisted regardless of disease status (AUCs for Barcelona Clinic Liver Cancer stages 0, A, B, and C were 0.888, 0.888, 0.901, and 0.881, respectively). The microRNA panel can also differentiate HCC from healthy (AUC 0.941), chronic hepatitis B (AUC 0.842), and cirrhosis (AUC 0.884), respectively.

High Expression of Macrophage Colony-Stimulating Factor in Peritumoral Liver Tissue Is Associated With Poor Survival After Curative Resection of Hepatocellular Carcinoma

Abstract: Purpose To investigate prognostic values of the intratumoral and peritumoral expression of macrophage colony-stimulating factors (M-CSF) in hepatocellular carcinoma (HCC) patients after curative resection. Patients and Methods Expression of M-CSF and density of macrophages (MΦ) were assessed by immunohistochemistry in tissue microarrays containing paired tumor and peritumoral liver tissue from 105 patients who had undergone hepatectomy for histologically proven HCC. Prognostic value of these and other clinicopathologic factors was evaluated. Results Neither intratumoral M-CSF nor MΦ density was associated with overall survival (OS) or disease-free survival (DFS). High peritumoral M-CSF and MΦ density, which correlated with large tumor size, presence of intrahepatic metastasis, and high TNM stage, were independent prognostic factors for both OS (P = .001 and P < .001, respectively) and DFS (P = .001 and P = .003, respectively) and affected incidence of early recurrence. In a small HCC subset, peritumoral M...

Estrogen regulates Hippo signaling via GPER in breast cancer.

Abstract: The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis.

A plasma microRNA panel for early detection of colorectal cancer

Abstract: Colonoscopy remains the standard screening method for detecting colorectal cancer (CRC) at an early stage. However, many people avoid having a colonoscopy because of the fear for its potential complications. Our study aimed to identify plasma microRNAs for preliminarily screening CRC in general population, so that some unnecessary colonoscopies can be avoided. We investigated plasma microRNA expression in three independent cohorts including the discovery (n = 80), training (n = 112), and validation (n = 49) phases recruited at two medical centers. Microarrays were used for screening 723 microRNAs in 80 plasma samples to identify candidate microRNAs. Quantitative reverse-transcriptase PCR was performed on the 161 training and validation plasma samples to evaluate the candidate microRNAs discovered from microarrays. A logistic regression model was constructed based on the training cohort and then verified by using the validation dataset. Area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified a panel of miR-409-3p, miR-7, and miR-93 that yielded high diagnostic accuracy in discriminating CRC from healthy group (AUC: 0.866 and 0.897 for training and validation dataset, respectively). Moreover, the diagnostic performance of the microRNA panel persisted in nonmetastasis CRC stages (Dukes' A-B, AUC: 0.809 and 0.892 for training and validation dataset, respectively) and in metastasis CRC stages (Dukes' C-D, AUC: 0.917 and 0.865 for training and validation dataset, respectively). In conclusion, our study reveals a plasma microRNA panel that has potential clinical value in early CRC detection and would play a critical role on preliminarily screening CRC in general population.

Human miR-1228 as a stable endogenous control for the quantification of circulating microRNAs in cancer patients.

Abstract: Circulating microRNAs are promising biomarkers for non-invasive testing and dynamic monitoring in cancer patients However, no consensus exists regarding the normalization of circulating microRNAs in the quantification, making the results incomparable We investigated global circulating microRNA profiles to identify a stable endogenous control for quantifying circulating microRNAs using three cohorts (n = 544), including 168 control individuals (healthy subjects and those with chronic hepatitis B and cirrhosis) and 376 cancer patients (hepatocellular, colorectal, lung, esophageal, gastric, renal, prostate, and breast cancer patients) GeNorm, NormFinder, and coefficient of variability (CV) were used to select the most stable endogenous control, whereas Ingenuity Pathway Analysis (IPA) was adopted to explore its signaling pathways Seven candidates (miR-1225-3p, miR-1228, miR-30d, miR-939, miR-940, miR-188-5p, and miR-134) from microarray analysis and four commonly used controls (miR-16, miR-223, let-7a, and RNU6B) from literature were subjected to real-time quantitative reverse transcription-polymerase chain reaction validation using independent cohorts MiR-1228 (CV = 54%) with minimum M value and S value presented as the most stable endogenous control across eight cancer types and three controls IPA showed miR-1228 to be involved extensively in metabolism-related signal pathways and organ morphology, implying that miR-1228 functions as a housekeeping gene Functional network analysis found that "hematological system development" was on the list of the top networks that associate with miR-1228, implying that miR-1228 plays an important role in the hematological system The results explained the steady expression of miR-1228 in the blood In conclusion, miR-1228 is a promising stable endogenous control for quantifying circulating microRNAs in cancer patients

Tumour-associated macrophages as treatment targets in oncology

Abstract: Macrophages are crucial drivers of tumour-promoting inflammation. Tumour-associated macrophages (TAMs) contribute to tumour progression at different levels: by promoting genetic instability, nurturing cancer stem cells, supporting metastasis, and taming protective adaptive immunity. TAMs can exert a dual, yin-yang influence on the effectiveness of cytoreductive therapies (chemotherapy and radiotherapy), either antagonizing the antitumour activity of these treatments by orchestrating a tumour-promoting, tissue-repair response or, instead, enhancing the overall antineoplastic effect. TAMs express molecular triggers of checkpoint proteins that regulate T-cell activation, and are targets of certain checkpoint-blockade immunotherapies. Other macrophage-centred approaches to anticancer therapy are under investigation, and include: inhibition of macrophage recruitment to, and/or survival in, tumours; functional re-education of TAMs to an antitumour, 'M1-like' mode; and tumour-targeting monoclonal antibodies that elicit macrophage-mediated extracellular killing, or phagocytosis and intracellular destruction of cancer cells. The evidence supporting these strategies is reviewed herein. We surmise that TAMs can provide tools to tailor the use of cytoreductive therapies and immunotherapy in a personalized medicine approach, and that TAM-focused therapeutic strategies have the potential to complement and synergize with both chemotherapy and immunotherapy.

MicroRNA profiling: approaches and considerations.

Abstract: MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate the expression of thousands of genes in a broad range of organisms in both normal physiological contexts and in disease contexts. miRNA expression profiling is gaining popularity because miRNAs, as key regulators in gene expression networks, can influence many biological processes and also show promise as biomarkers for disease. Technological advances have spawned a multitude of platforms for miRNA profiling, and an understanding of the strengths and pitfalls of different approaches can aid in their effective use. Here, we review the major considerations for carrying out and interpreting results of miRNA-profiling studies.