National Institutes of Health, a Component of the US Dept. of Health & Human Services

The Ohio State University

Fudan University

The United States of America As Represented by the Secretary of

The United States of America As Represented by the Department of Health

The Ohio State Research Foundation

Xin Wei Wang

Curtis C Harris

Albert J Fornace, Jr

Qimin Zhan

Jill D Coursen

Carlo M Croce

Jan H J Hoeijmakers

Jennifer Thomas

Leonard W Mayer

Cynthia Hatcher

Vivian Takafuji

Raydel Anderson

Mary Jordan Theodore

Paul K Goldsmith

Stephanie K Roessler

Junfang Ji

Zhao-you Tang

Taro Yamashita

Anuradha Budhu

Masahiro Seike

Valerie Fako Miller

Jan H Hoeijmakers

Hui-chuan Sun

Anuradha Budha

This disclosure provides methods for predicting the likelihood that a hepatocellular carcinoma (HCC) will respond to transcatheter arterial chemoembolization (TACE) using a gene signature of 14 or 15 genes. Also provided are nucleic acid probes and kits for detecting the gene signature.

Gene signature predictive of hepatocellular carcinoma response to transcatheter arterial chemoembolization (TACE)

A process for detectingnucleic acid in a sample includes producing an amplification product by amplifying anucleotide sequence and measuring the amplification product to detectin the sample. Some embodiments allow direct serotype determination in a single step assay. Also provided are reagents and methods for detecting and distinguishingfrom other infectious agents. A kit is provided for detecting and quantifyingin a sample.

Selective detection of

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Methods are disclosed for determining the prognosis of a subject with an adenocarcinoma in an organ, such as the lung. The methods can include quantitating expression of a plurality of cytokines of interest, such as IL-1a, IL-1b, IL-2, IL-8, IL-10, IL-12, IL-15, IFN-&#x3b3; and TNF-a in the adenocarcinoma and in non-cancerous tissue in the organ. Altered expression of IL-1a, IL-1b, IL-2, IL-8, IL-10, IL-12, IL-15, IFN-&#x3b3; and TNF-a in the adenocarcinoma as compared to a control and in non-cancerous tissue in the organ as compared to a control determines the prognosis for the subject. Methods for determining if a therapeutic agent is effective as an anti-cancer agent are also disclosed.

Methods of determining the prognosis of an adenocarcinoma

Disclosed herein is a driver gene signature for predicting survival in patients with solid tumors, such as hepatocellular carcinoma (HCC) and breast cancer. The gene signature includes ten tumor-associated genes, SH2D4A, CCDC25, ELP3, DLC1, PROSC, SORBS3, HNRPD, PAQR3, PHF17 and DCK. A decrease in DNA copy number or mRNA expression of SH2D4A, CCDC25, ELP3, DLC1, PROSC and SORBS3 in solid tumors is associated with a poor prognosis, while a decrease in DNA copy number or mRNA expression of HNRPD, PAQR3, PHF17 and DCK in solid tumors is associated with a good prognosis. Methods of predicting the prognosis of a patient diagnosed with HCC or breast cancer by detecting expression of one of more tumor-associated genes, and methods of treating a patient diagnosed with HCC or breast cancer by administering an agent that alters expression or activity of one or more of the disclosed tumor-associated genes, are described.

Gene signature for predicting prognosis of patients with solid tumors

It is disclosed herein that expression of microRNA-26 is decreased in hepatocellular (HCC) tumor tissue relative to non-cancerous tissue, and that a low level of microRNA-26 is associated with a poor clinical outcome. It is also disclosed herein that a low expression level of microRNA-26 is correlated with a favorable response to interferon (IFN)-&#x3b1; therapy in HCC patients. Thus, provided herein is a method of predicting the clinical outcome of a patient diagnosed with HCC comprising detecting the level of microRNA-26 expression in a sample obtained from the patient. Also provided is a method of selecting a patient diagnosed with HCC as a candidate for IFN-&#x3b1; therapy, comprising detecting the level of microRNA-26 expression in a sample obtained from the patient. A method of identifying therapeutic agents for the treatment of HCC, comprising screening candidate agents in vitro to select an agent that increases expression of microRNA-26 in HCC cells are also provided. Further provided are methods of treating a patient diagnosed with HCC and expressing a low level of miR-26, wherein treatment comprises IFN-&#x3b1; therapy.

Use of MiR-26 family as a predictive marker for hepatocellular carcinoma and responsiveness to therapy

Disclosed herein is a driver gene signature for predicting survival in patients with solid tumors, such as hepatocellular carcinoma (HCC) and breast cancer. The gene signature includes ten tumor-associated genes, SH2D4A, CCDC25, ELP3, DLC1, PROSC, SORBS3, HNRPD, PAQR3, PHF17 and DCK. A decrease in DNA copy number or mRNA expression of SH2D4A, CCDC25, ELP3, DLC1, PROSC and SORBS3 in solid tumors is associated with a poor prognosis, while a decrease in DNA copy number or mRNA expression of HNRPD, PAQR3, PHF17 and DCK in solid tumors is associated with a good prognosis. Thus, provided herein is a method of predicting the prognosis of a patient diagnosed with HCC or breast cancer by detecting expression of one of more tumor-associated genes in a tumor sample and comparing expression of the one or more tumor-associated genes in the tumor sample to a control. Also provided is a method of treating a patient diagnosed with HCC or breast cancer by administering a therapeutically effective amount of an agent that alters expression or activity of one or more of the disclosed tumor-associated genes. Further provided are arrays comprising probes or antibodies specific for a plurality of tumor-associated genes or proteins.

Based on the observation of the cooperation of osteopontin (OPN) and matrixmetalloproteinase-9 (MMP-9) in the promotion of the metastatic phenotype, therapies and diagnostic assays are disclosed for the treatment of a tumor that overexpresses OPN, such as hepatocellular carcinoma (HCC), for example metastatic HCC. In one example, methods of treating a tumor include administration of an agent that reduces cellular invasion resulting from the interaction between a fragment of OPN (OPN-5kD) generated by MMP-9 cleavage and CD44 receptor. Examples of such agents include fragments of OPN-5kD and antibodies specific for OPN-5kD. Therapeutic compositions are also provided that include such agents. Also provided are methods of diagnosing or prognosing a tumor, for example by detecting expression of OPN-5kD peptide or OPN-c mRNA in a biological sample obtained from the subject. Also provided are antibodies that specifically bind OPN-5kD.

Compositions and methods for diagnosis and treatment of tumors

The invention provides a method of determining an HCC subtype in a subject comprising a) obtaining a sample from the subject, b) assaying the sample to detect the expression of 1 or more biomarkers, and c) correlating the expression of the biomarkers with an HCC subtype in a subject. The invention further provides methods of detecting HCC stem cells in a sample. Additionally, the invention provides methods and compositions for treating subjects with HCC that take advantage of the biomarkers associated with HCC stem cells.

Methods for determining heptocellular carcinoma subtype and detecting hepatic cancer stem cells

Provided herein are methods and compositions for the diagnosis, prognosis and treatment of Hepatocellular carcinoma (HCC). Also provided are methods of identifying anti-HCC agents.

MicroRNA expression signature for predicting survival and metastases in hepatocellular carcinoma

The present invention is directed to novel methods for assaying for modulators of GADD45 polypeptide activity. The invention also provides means to sensitize a proliferating cell to a DNA base-damaging agent by administration of novel inhibitors of GADD45 polypeptide activity. The invention further provides polypeptides which interfere with the ability of Cdc2/cyclin B1 complexes to cause a pause at the G2/M stage of the cell cycle in response to GADD45, and nucleic acids which encode such polypeptides.

Method of identifying inhibitors of GADD45 polypeptide activity, and inhibitors of such activity

This invention relates to methods of screening for compounds capable of inducing apoptosis in certain tumor cells. The invention also relates to compounds identified by such methods. In addition, the invention relates to methods for the in vitro diagnosis ofand compounds useful in these methods.

Growing community of inventors

Rockville, MD, United States of America

Xin Wei Wang