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Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients
Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully explored and...
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| Published in: | Scientific reports 2021-06, Vol.11 (1), p.11765-11765, Article 11765 |
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| description | Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully explored and still remains obscure. This study is aimed towards the identification of genes and pathways implicated in the EOCRC. In the present study, we performed high throughput RNA sequencing of colorectal tumor tissues for four EOCRC (median age 43.5 years) samples with adjacent mucosa and performed subsequent bioinformatics analysis to identify novel deregulated pathways and genes. Our integrated analysis identifies 17 hub genes (
INSR, TNS1, IL1RAP, CD22, FCRLA, CXCL3, HGF, MS4A1, CD79B, CXCR2, IL1A, PTPN11, IRS1, IL1B, MET, TCL1A
, and
IL1R1
). Pathway analysis of identified genes revealed that they were involved in the MAPK signaling pathway, hematopoietic cell lineage, cytokine–cytokine receptor pathway and PI3K-Akt signaling pathway. Survival and stage plot analysis identified four genes
CXCL3, IL1B, MET
and
TNS1
genes (
p
= 0.015, 0.038, 0.049 and 0.011 respectively), significantly associated with overall survival. Further, differential expression of
TNS1
and
MET
were confirmed on the validation cohort of the 5 EOCRCs (median age |
| doi_str_mv | 10.1038/s41598-021-91154-x |
| format | article |
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INSR, TNS1, IL1RAP, CD22, FCRLA, CXCL3, HGF, MS4A1, CD79B, CXCR2, IL1A, PTPN11, IRS1, IL1B, MET, TCL1A
, and
IL1R1
). Pathway analysis of identified genes revealed that they were involved in the MAPK signaling pathway, hematopoietic cell lineage, cytokine–cytokine receptor pathway and PI3K-Akt signaling pathway. Survival and stage plot analysis identified four genes
CXCL3, IL1B, MET
and
TNS1
genes (
p
= 0.015, 0.038, 0.049 and 0.011 respectively), significantly associated with overall survival. Further, differential expression of
TNS1
and
MET
were confirmed on the validation cohort of the 5 EOCRCs (median age < 50 years and sporadic origin). This is the first approach to find early age onset biomarkers in Indian CRC patients. Among these
TNS1
and
MET
are novel for EOCRC and may serve as potential biomarkers and novel therapeutic targets in future.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-021-91154-x</identifier><identifier>PMID: 34083590</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>1-Phosphatidylinositol 3-kinase ; 631/337 ; 631/67 ; Adult ; Age ; Age of Onset ; Aged ; AKT protein ; Bioinformatics ; Biomarkers ; c-Met protein ; Cancer ; CD22 antigen ; Cell lineage ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Computational Biology - methods ; CXCR2 protein ; Cytokines ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Ontology ; Humanities and Social Sciences ; Humans ; India ; Interleukin 1 ; Male ; MAP kinase ; Middle Aged ; Molecular Sequence Annotation ; Mucosa ; multidisciplinary ; Protein Interaction Mapping - methods ; Protein Interaction Maps ; Rectum ; Science ; Science (multidisciplinary) ; Signal Transduction ; Transcriptome</subject><ispartof>Scientific reports, 2021-06, Vol.11 (1), p.11765-11765, Article 11765</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-1ae0c0e984dde7fdc2730277e198e1fcdecfe8f97543041b2497474ac30aa2403</citedby><cites>FETCH-LOGICAL-c540t-1ae0c0e984dde7fdc2730277e198e1fcdecfe8f97543041b2497474ac30aa2403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2536651956/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2536651956?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25751,27922,27923,37010,37011,44588,53789,53791,74896</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34083590$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Singh, Manish Pratap</creatorcontrib><creatorcontrib>Rai, Sandhya</creatorcontrib><creatorcontrib>Singh, Nand K.</creatorcontrib><creatorcontrib>Srivastava, Sameer</creatorcontrib><title>Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully explored and still remains obscure. This study is aimed towards the identification of genes and pathways implicated in the EOCRC. In the present study, we performed high throughput RNA sequencing of colorectal tumor tissues for four EOCRC (median age 43.5 years) samples with adjacent mucosa and performed subsequent bioinformatics analysis to identify novel deregulated pathways and genes. Our integrated analysis identifies 17 hub genes (
INSR, TNS1, IL1RAP, CD22, FCRLA, CXCL3, HGF, MS4A1, CD79B, CXCR2, IL1A, PTPN11, IRS1, IL1B, MET, TCL1A
, and
IL1R1
). Pathway analysis of identified genes revealed that they were involved in the MAPK signaling pathway, hematopoietic cell lineage, cytokine–cytokine receptor pathway and PI3K-Akt signaling pathway. Survival and stage plot analysis identified four genes
CXCL3, IL1B, MET
and
TNS1
genes (
p
= 0.015, 0.038, 0.049 and 0.011 respectively), significantly associated with overall survival. Further, differential expression of
TNS1
and
MET
were confirmed on the validation cohort of the 5 EOCRCs (median age < 50 years and sporadic origin). This is the first approach to find early age onset biomarkers in Indian CRC patients. Among these
TNS1
and
MET
are novel for EOCRC and may serve as potential biomarkers and novel therapeutic targets in future.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>631/337</subject><subject>631/67</subject><subject>Adult</subject><subject>Age</subject><subject>Age of Onset</subject><subject>Aged</subject><subject>AKT protein</subject><subject>Bioinformatics</subject><subject>Biomarkers</subject><subject>c-Met protein</subject><subject>Cancer</subject><subject>CD22 antigen</subject><subject>Cell lineage</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Computational Biology - methods</subject><subject>CXCR2 protein</subject><subject>Cytokines</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Ontology</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>India</subject><subject>Interleukin 1</subject><subject>Male</subject><subject>MAP kinase</subject><subject>Middle Aged</subject><subject>Molecular Sequence Annotation</subject><subject>Mucosa</subject><subject>multidisciplinary</subject><subject>Protein Interaction Mapping - methods</subject><subject>Protein Interaction Maps</subject><subject>Rectum</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signal Transduction</subject><subject>Transcriptome</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks1u1DAQxyMEolXpC3BAkbhwCfgzji9IaMXHSpWQUDlbs_Yk9SprL3a2dC88S5-lT4a3KaXlgC-2Z_7zG3v0r6qXlLylhHfvsqBSdw1htNGUStFcPamOGRGyYZyxpw_OR9VpzmtSlmRaUP28OuKCdFxqclz9Ok8Qsk1-O8WNt_UIwWULW6xjXyOkcV_DUC4h43QI2TjGhHaCsbYQLKaba-8wTL73mG-uQ7zEsR4wYK4Lqd7CdPET9iXjQ70MzkOoF98Wh7gvVflF9ayHMePp3X5Sff_08XzxpTn7-nm5-HDWWCnI1FBAYgnqTjiHqneWKU6YUkh1h7S3Dm2PXa-VFJwIumJCK6EEWE4AmCD8pFrOXBdhbbbJbyDtTQRvbgMxDQbS5O2IhjrrXKupxDLVdlWgwIXqe3SEdI5CYb2fWdvdaoPOln8kGB9BH2eCvzBDvDQdVZJzXQBv7gAp_thhnszGZ4tjmT3GXTZMctWKtnQt0tf_SNdxl0IZ1UHVtpJq2RYVm1U2xZwT9vePocQc3GJmt5jiFnPrFnNVil49_MZ9yR9vFAGfBbmkwoDpb-__YH8DHrfP-w</recordid><startdate>20210603</startdate><enddate>20210603</enddate><creator>Singh, Manish Pratap</creator><creator>Rai, Sandhya</creator><creator>Singh, Nand K.</creator><creator>Srivastava, Sameer</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20210603</creationdate><title>Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients</title><author>Singh, Manish Pratap ; Rai, Sandhya ; Singh, Nand K. ; Srivastava, Sameer</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-1ae0c0e984dde7fdc2730277e198e1fcdecfe8f97543041b2497474ac30aa2403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>631/337</topic><topic>631/67</topic><topic>Adult</topic><topic>Age</topic><topic>Age of Onset</topic><topic>Aged</topic><topic>AKT protein</topic><topic>Bioinformatics</topic><topic>Biomarkers</topic><topic>c-Met protein</topic><topic>Cancer</topic><topic>CD22 antigen</topic><topic>Cell lineage</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Computational Biology - methods</topic><topic>CXCR2 protein</topic><topic>Cytokines</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Ontology</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>India</topic><topic>Interleukin 1</topic><topic>Male</topic><topic>MAP kinase</topic><topic>Middle Aged</topic><topic>Molecular Sequence Annotation</topic><topic>Mucosa</topic><topic>multidisciplinary</topic><topic>Protein Interaction Mapping - methods</topic><topic>Protein Interaction Maps</topic><topic>Rectum</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signal Transduction</topic><topic>Transcriptome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Singh, Manish Pratap</creatorcontrib><creatorcontrib>Rai, Sandhya</creatorcontrib><creatorcontrib>Singh, Nand K.</creatorcontrib><creatorcontrib>Srivastava, Sameer</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Singh, Manish Pratap</au><au>Rai, Sandhya</au><au>Singh, Nand K.</au><au>Srivastava, Sameer</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2021-06-03</date><risdate>2021</risdate><volume>11</volume><issue>1</issue><spage>11765</spage><epage>11765</epage><pages>11765-11765</pages><artnum>11765</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully explored and still remains obscure. This study is aimed towards the identification of genes and pathways implicated in the EOCRC. In the present study, we performed high throughput RNA sequencing of colorectal tumor tissues for four EOCRC (median age 43.5 years) samples with adjacent mucosa and performed subsequent bioinformatics analysis to identify novel deregulated pathways and genes. Our integrated analysis identifies 17 hub genes (
INSR, TNS1, IL1RAP, CD22, FCRLA, CXCL3, HGF, MS4A1, CD79B, CXCR2, IL1A, PTPN11, IRS1, IL1B, MET, TCL1A
, and
IL1R1
). Pathway analysis of identified genes revealed that they were involved in the MAPK signaling pathway, hematopoietic cell lineage, cytokine–cytokine receptor pathway and PI3K-Akt signaling pathway. Survival and stage plot analysis identified four genes
CXCL3, IL1B, MET
and
TNS1
genes (
p
= 0.015, 0.038, 0.049 and 0.011 respectively), significantly associated with overall survival. Further, differential expression of
TNS1
and
MET
were confirmed on the validation cohort of the 5 EOCRCs (median age < 50 years and sporadic origin). This is the first approach to find early age onset biomarkers in Indian CRC patients. Among these
TNS1
and
MET
are novel for EOCRC and may serve as potential biomarkers and novel therapeutic targets in future.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34083590</pmid><doi>10.1038/s41598-021-91154-x</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Scientific reports, 2021-06, Vol.11 (1), p.11765-11765, Article 11765 |
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| language | eng |
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| source | Publicly Available Content Database; PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 1-Phosphatidylinositol 3-kinase 631/337 631/67 Adult Age Age of Onset Aged AKT protein Bioinformatics Biomarkers c-Met protein Cancer CD22 antigen Cell lineage Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Computational Biology - methods CXCR2 protein Cytokines Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Ontology Humanities and Social Sciences Humans India Interleukin 1 Male MAP kinase Middle Aged Molecular Sequence Annotation Mucosa multidisciplinary Protein Interaction Mapping - methods Protein Interaction Maps Rectum Science Science (multidisciplinary) Signal Transduction Transcriptome |
| title | Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients |
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