Oncofetal Gene SALL4 in Aggressive Hepatocellular Carcinoma
SALL4, which is expressed in fetal but not adult liver, is reexpressed in a subgroup of hepatocellular cancers associated with a poor prognosis. In mice, treatment aimed at inhibiting SALL4 has antitumor effects. Hepatocellular carcinoma is the third leading cause of cancer-related deaths globally....
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| Published in | The New England journal of medicine Vol. 368; no. 24; pp. 2266 - 2276 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Waltham, MA
Massachusetts Medical Society
13.06.2013
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| Subjects | |
| Online Access | Get full text |
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| Abstract | SALL4,
which is expressed in fetal but not adult liver, is reexpressed in a subgroup of hepatocellular cancers associated with a poor prognosis. In mice, treatment aimed at inhibiting
SALL4
has antitumor effects.
Hepatocellular carcinoma is the third leading cause of cancer-related deaths globally. Although the epidemiologic risk factors for hepatocellular carcinoma are well known,
1
the molecular mechanisms underlying hepatocarcinogenesis are not well characterized. Elucidation of these mechanisms may allow identification of new candidates for therapeutic targeting. Although surgery, liver transplantation, and radiologic intervention may be viable options for patients with early-stage disease, the prognosis associated with advanced-stage hepatocellular carcinoma remains bleak.
2
Combination chemotherapy has not improved overall survival but has nonetheless been in wide use for many years because of its possible role in palliation. The need to understand the molecular pathogenesis . . . |
|---|---|
| AbstractList | Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment.
We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays.
SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in SALL4-positive hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4-corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo.
SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma. (Funded by the Singapore National Medical Research Council and others.). BackgroundHepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment.MethodsWe screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays.ResultsSALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in SALL4-positive hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4–corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo.ConclusionsSALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma. (Funded by the Singapore National Medical Research Council and others.) SALL4, which is expressed in fetal but not adult liver, is reexpressed in a subgroup of hepatocellular cancers associated with a poor prognosis. In mice, treatment aimed at inhibiting SALL4 has antitumor effects. Hepatocellular carcinoma is the third leading cause of cancer-related deaths globally. Although the epidemiologic risk factors for hepatocellular carcinoma are well known, 1 the molecular mechanisms underlying hepatocarcinogenesis are not well characterized. Elucidation of these mechanisms may allow identification of new candidates for therapeutic targeting. Although surgery, liver transplantation, and radiologic intervention may be viable options for patients with early-stage disease, the prognosis associated with advanced-stage hepatocellular carcinoma remains bleak. 2 Combination chemotherapy has not improved overall survival but has nonetheless been in wide use for many years because of its possible role in palliation. The need to understand the molecular pathogenesis . . . |
| Author | Srivastava, Supriya Dimitrov, Todor Gao, Chong Lim, Joline S.J Chai, Li Yang, Henry Yong, Kol Jia Ravikumar, Sharada Kawasaki, Akira Dan, Yock Young Tenen, Daniel G Yan, Benedict Luk, John M Salto-Tellez, Manuel Wong, Kwong-Fai Ong, Chee Wee Fan, Sheung Tat Lee, Sanghoon Tian, Xi Poon, Ronnie T |
| Author_xml | – sequence: 1 givenname: Kol Jia surname: Yong fullname: Yong, Kol Jia organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 2 givenname: Chong surname: Gao fullname: Gao, Chong organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 3 givenname: Joline S.J surname: Lim fullname: Lim, Joline S.J organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 4 givenname: Benedict surname: Yan fullname: Yan, Benedict organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 5 givenname: Henry surname: Yang fullname: Yang, Henry organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 6 givenname: Todor surname: Dimitrov fullname: Dimitrov, Todor organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 7 givenname: Akira surname: Kawasaki fullname: Kawasaki, Akira organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 8 givenname: Chee Wee surname: Ong fullname: Ong, Chee Wee organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 9 givenname: Kwong-Fai surname: Wong fullname: Wong, Kwong-Fai organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 10 givenname: Sanghoon surname: Lee fullname: Lee, Sanghoon organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 11 givenname: Sharada surname: Ravikumar fullname: Ravikumar, Sharada organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 12 givenname: Supriya surname: Srivastava fullname: Srivastava, Supriya organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 13 givenname: Xi surname: Tian fullname: Tian, Xi organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 14 givenname: Ronnie T surname: Poon fullname: Poon, Ronnie T organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 15 givenname: Sheung Tat surname: Fan fullname: Fan, Sheung Tat organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 16 givenname: John M surname: Luk fullname: Luk, John M organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 17 givenname: Yock Young surname: Dan fullname: Dan, Yock Young organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 18 givenname: Manuel surname: Salto-Tellez fullname: Salto-Tellez, Manuel organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 19 givenname: Li surname: Chai fullname: Chai, Li organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) – sequence: 20 givenname: Daniel G surname: Tenen fullname: Tenen, Daniel G organization: From the Cancer Science Institute of Singapore (K.J.Y., H.Y., A.K., C.W.O., K.-F.W., S.L., S.R., S.S., J.M.L., M.S.-T., D.G.T.), the National University of Singapore Graduate School for Integrative Sciences and Engineering (K.J.Y.), the National University Cancer Institute (J.S.J.L.), and the Departments of Pathology (B.Y.), Pharmacology (J.M.L.), and Medicine (Y.Y.D.), National University Health System and National University of Singapore, Singapore; the Department of Pathology, Brigham and Women's Hospital (C.G., J.S.J.L., T.D., X.T., L.C.), and the Harvard Stem Cell Institute (D.G.T.), Harvard Medical School, Boston; the Department of Surgery, Queen Mary Hospital, Hong Kong (R.T.P., S.T.F., J.M.L.); and the Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, United Kingdom (M.S.-T.) |
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| Keywords | Medicine Liver cancer Gene Digestive diseases Hepatic disease Hepatocellular carcinoma Genetics Malignant tumor Cancer High malignancy |
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| Snippet | SALL4,
which is expressed in fetal but not adult liver, is reexpressed in a subgroup of hepatocellular cancers associated with a poor prognosis. In mice,... Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with... BackgroundHepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas,... BACKGROUNDHepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas,... |
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| SubjectTerms | Adult Animals Biological and medical sciences Biomarkers, Tumor - metabolism Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Cell survival Fetuses Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Gene Expression Regulation, Neoplastic General aspects Hepatocellular carcinoma Humans Leukemia Liver - metabolism Liver cancer Liver cirrhosis Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical research Medical sciences Metabolic Networks and Pathways - physiology Metastases Mice Mice, Inbred Strains Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Patients Phenotypes Progenitor cells Prognosis PTEN Phosphohydrolase - metabolism PTEN protein Rodents Statistical analysis Stem cells Tensin Transcription Factors - antagonists & inhibitors Transcription Factors - genetics Transcription Factors - metabolism Transplantation, Heterologous Tumor Cells, Cultured Tumorigenicity Tumors Xenografts |
| Title | Oncofetal Gene SALL4 in Aggressive Hepatocellular Carcinoma |
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