A five-gene signature as a potential predictor of metastasis and survival in colorectal cancer
To understand the molecular mechanisms of metastasis and prognosis of colorectal cancer (CRC), we isolated single cell‐derived progenies (SCPs) from SW480 cells in vitro and compared their metastatic potential in an orthotopic CRC tumour model in vivo. Two groups of SCPs with the capability of high...
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| Veröffentlicht in: | The Journal of pathology 2010-03, Vol.220 (4), p.475-489 |
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| description | To understand the molecular mechanisms of metastasis and prognosis of colorectal cancer (CRC), we isolated single cell‐derived progenies (SCPs) from SW480 cells in vitro and compared their metastatic potential in an orthotopic CRC tumour model in vivo. Two groups of SCPs with the capability of high and low metastasis, respectively, were obtained. By analysing the gene expression profiles of high (SCP51), low (SCP58) metastatic SCPs, and their parental cell line (SW480/EGFP), we demonstrated that 143 genes were differentially expressed either between SCP51 and SCP58 or between SCP58 and SW480/EGFP. Gene‐annotation enrichment analysis of DAVID revealed 80 genes in the top ten clusters of the analysis (gene enrichment score > 1). Of the 80‐gene set, 32 genes are potentially involved in metastasis, as revealed by Geneclip. Five putative metastatic genes (LYN, SDCBP, MAP4K4, DKK1, and MID1) were selected for further validations. Immunohistochemical analysis in a cohort of 181 CRC clinical samples showed that the individual expression of LYN, MAP4K4, and MID1, as well as the five‐gene signature, was closely correlated with lymph node metastasis in CRC patients. More importantly, the individual expression of LYN, MAP4K4, SDCBP, and MID1, as well as the five‐gene signature, was significantly correlated with overall survival in CRC patients. Thus, our five‐gene signature may be able to predict metastasis and survival of CRC in the clinic, and opens new perspectives on the biology of CRC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/path.2668 |
| format | Article |
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Two groups of SCPs with the capability of high and low metastasis, respectively, were obtained. By analysing the gene expression profiles of high (SCP51), low (SCP58) metastatic SCPs, and their parental cell line (SW480/EGFP), we demonstrated that 143 genes were differentially expressed either between SCP51 and SCP58 or between SCP58 and SW480/EGFP. Gene‐annotation enrichment analysis of DAVID revealed 80 genes in the top ten clusters of the analysis (gene enrichment score > 1). Of the 80‐gene set, 32 genes are potentially involved in metastasis, as revealed by Geneclip. Five putative metastatic genes (LYN, SDCBP, MAP4K4, DKK1, and MID1) were selected for further validations. Immunohistochemical analysis in a cohort of 181 CRC clinical samples showed that the individual expression of LYN, MAP4K4, and MID1, as well as the five‐gene signature, was closely correlated with lymph node metastasis in CRC patients. More importantly, the individual expression of LYN, MAP4K4, SDCBP, and MID1, as well as the five‐gene signature, was significantly correlated with overall survival in CRC patients. Thus, our five‐gene signature may be able to predict metastasis and survival of CRC in the clinic, and opens new perspectives on the biology of CRC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.2668</identifier><identifier>PMID: 20077526</identifier><identifier>CODEN: JPTLAS</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; Biological and medical sciences ; Cell Proliferation ; Colorectal cancer ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Dkk1 protein ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene expression ; Gene Expression Profiling - methods ; gene signature ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Lymph nodes ; Lyn protein ; Male ; Medical sciences ; Metastases ; metastasis ; Mice ; Mice, Nude ; Molecular modelling ; Neoplasm Metastasis - genetics ; Neoplasm Metastasis - pathology ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Neoplasm Transplantation ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - physiology ; Oligonucleotide Array Sequence Analysis - methods ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Progeny ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction - methods ; single cell-derived progenies ; Single-cell protein ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Survival ; Survival Analysis ; Tumor Cells, Cultured ; Tumors</subject><ispartof>The Journal of pathology, 2010-03, Vol.220 (4), p.475-489</ispartof><rights>Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5258-b7f3f54d721a41090e58688052411a1e132ff828fe24ab3164129767b1ffae4f3</citedby><cites>FETCH-LOGICAL-c5258-b7f3f54d721a41090e58688052411a1e132ff828fe24ab3164129767b1ffae4f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpath.2668$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.2668$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22363322$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20077526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hao, Jun-Mei</creatorcontrib><creatorcontrib>Chen, Juan-Zhi</creatorcontrib><creatorcontrib>Sui, Hong-Mei</creatorcontrib><creatorcontrib>Si-Ma, Xue-Qing</creatorcontrib><creatorcontrib>Li, Guang-Qiu</creatorcontrib><creatorcontrib>Liu, Chao</creatorcontrib><creatorcontrib>Li, Ji-Liang</creatorcontrib><creatorcontrib>Ding, Yan-Qing</creatorcontrib><creatorcontrib>Li, Jian-Ming</creatorcontrib><title>A five-gene signature as a potential predictor of metastasis and survival in colorectal cancer</title><title>The Journal of pathology</title><addtitle>J. Pathol</addtitle><description>To understand the molecular mechanisms of metastasis and prognosis of colorectal cancer (CRC), we isolated single cell‐derived progenies (SCPs) from SW480 cells in vitro and compared their metastatic potential in an orthotopic CRC tumour model in vivo. Two groups of SCPs with the capability of high and low metastasis, respectively, were obtained. By analysing the gene expression profiles of high (SCP51), low (SCP58) metastatic SCPs, and their parental cell line (SW480/EGFP), we demonstrated that 143 genes were differentially expressed either between SCP51 and SCP58 or between SCP58 and SW480/EGFP. Gene‐annotation enrichment analysis of DAVID revealed 80 genes in the top ten clusters of the analysis (gene enrichment score > 1). Of the 80‐gene set, 32 genes are potentially involved in metastasis, as revealed by Geneclip. Five putative metastatic genes (LYN, SDCBP, MAP4K4, DKK1, and MID1) were selected for further validations. Immunohistochemical analysis in a cohort of 181 CRC clinical samples showed that the individual expression of LYN, MAP4K4, and MID1, as well as the five‐gene signature, was closely correlated with lymph node metastasis in CRC patients. More importantly, the individual expression of LYN, MAP4K4, SDCBP, and MID1, as well as the five‐gene signature, was significantly correlated with overall survival in CRC patients. Thus, our five‐gene signature may be able to predict metastasis and survival of CRC in the clinic, and opens new perspectives on the biology of CRC. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Dkk1 protein</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - methods</subject><subject>gene signature</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Lymph nodes</subject><subject>Lyn protein</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metastases</subject><subject>metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Molecular modelling</subject><subject>Neoplasm Metastasis - genetics</subject><subject>Neoplasm Metastasis - pathology</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neoplasm Transplantation</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - physiology</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Progeny</subject><subject>Prognosis</subject><subject>Reverse Transcriptase Polymerase Chain Reaction - methods</subject><subject>single cell-derived progenies</subject><subject>Single-cell protein</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. 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Liver. Pancreas. Abdomen</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>gene signature</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Lymph nodes</topic><topic>Lyn protein</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metastases</topic><topic>metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Molecular modelling</topic><topic>Neoplasm Metastasis - genetics</topic><topic>Neoplasm Metastasis - pathology</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neoplasm Transplantation</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Neoplastic Stem Cells - physiology</topic><topic>Oligonucleotide Array Sequence Analysis - methods</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. 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Pathol</addtitle><date>2010-03</date><risdate>2010</risdate><volume>220</volume><issue>4</issue><spage>475</spage><epage>489</epage><pages>475-489</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><coden>JPTLAS</coden><abstract>To understand the molecular mechanisms of metastasis and prognosis of colorectal cancer (CRC), we isolated single cell‐derived progenies (SCPs) from SW480 cells in vitro and compared their metastatic potential in an orthotopic CRC tumour model in vivo. Two groups of SCPs with the capability of high and low metastasis, respectively, were obtained. By analysing the gene expression profiles of high (SCP51), low (SCP58) metastatic SCPs, and their parental cell line (SW480/EGFP), we demonstrated that 143 genes were differentially expressed either between SCP51 and SCP58 or between SCP58 and SW480/EGFP. Gene‐annotation enrichment analysis of DAVID revealed 80 genes in the top ten clusters of the analysis (gene enrichment score > 1). Of the 80‐gene set, 32 genes are potentially involved in metastasis, as revealed by Geneclip. Five putative metastatic genes (LYN, SDCBP, MAP4K4, DKK1, and MID1) were selected for further validations. Immunohistochemical analysis in a cohort of 181 CRC clinical samples showed that the individual expression of LYN, MAP4K4, and MID1, as well as the five‐gene signature, was closely correlated with lymph node metastasis in CRC patients. More importantly, the individual expression of LYN, MAP4K4, SDCBP, and MID1, as well as the five‐gene signature, was significantly correlated with overall survival in CRC patients. Thus, our five‐gene signature may be able to predict metastasis and survival of CRC in the clinic, and opens new perspectives on the biology of CRC. Copyright © 2009 Pathological Society of Great Britain and Ireland. 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| subjects | Animals Biological and medical sciences Cell Proliferation Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Dkk1 protein Female Gastroenterology. Liver. Pancreas. Abdomen Gene expression Gene Expression Profiling - methods gene signature Humans Investigative techniques, diagnostic techniques (general aspects) Lymph nodes Lyn protein Male Medical sciences Metastases metastasis Mice Mice, Nude Molecular modelling Neoplasm Metastasis - genetics Neoplasm Metastasis - pathology Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Neoplasm Transplantation Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - physiology Oligonucleotide Array Sequence Analysis - methods Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Progeny Prognosis Reverse Transcriptase Polymerase Chain Reaction - methods single cell-derived progenies Single-cell protein Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Survival Survival Analysis Tumor Cells, Cultured Tumors |
| title | A five-gene signature as a potential predictor of metastasis and survival in colorectal cancer |
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