B3GNT3 Expression Is a Novel Marker Correlated with Pelvic Lymph Node Metastasis and Poor Clinical Outcome in Early-Stage Cervical Cancer
The β1,3-N-acetylglucosaminyltransferase-3 gene (B3GNT3) encodes a member of the B3GNT family that functions as the backbone structure of dimeric sialyl-Lewis A and is involved in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. B3GNT3 has been implicated as an important...
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description | The β1,3-N-acetylglucosaminyltransferase-3 gene (B3GNT3) encodes a member of the B3GNT family that functions as the backbone structure of dimeric sialyl-Lewis A and is involved in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. B3GNT3 has been implicated as an important element in the development of certain cancers. However, the characteristics of B3GNT3 in the development and progression of cancer remain largely unknown. Thus, our study aimed to investigate the expression pattern and the prognostic value of B3GNT3 in patients with early-stage cervical cancer.
The mRNA and protein levels of B3GNT3 expression were examined in eight cervical cancer cell lines and ten paired cervical cancer tumors, using real-time PCR and western blotting, respectively. Immunohistochemistry (IHC) was used to analyze B3GNT3 protein expression in paraffin-embedded tissues from 196 early-stage cervical cancer patients. Statistical analyses were applied to evaluate the association between B3GNT3 expression scores and clinical parameters, as well as patient survival.
B3GNT3 expression was significantly upregulated in cervical cancer cell lines and lesions compared with normal cells and adjacent noncancerous cervical tissues. In the 196 cases of tested early-stage cervical cancer samples, the B3GNT3 protein level was positively correlated with high risk TYPES of human papillomavirus (HPV) infection (P = 0.026), FIGO stage (P < 0.001), tumor size (P = 0.025), tumor recurrence (P = 0.004), vital status (P < 0.001), concurrent chemotherapy and radiotherapy (P = 0.016), lymphovascular space involvement (P = 0.003) and most importantly, lymph node metastasis (P = 0.003). Patients with high B3GNT3 expression had a shorter overall survival (OS) and disease-free survival (DFS) compared with those with low expression of this protein. Multivariate analysis suggested that B3GNT3 expression is an independent prognostic indicator for cervical cancer patients.
Our study demonstrated that elevated B3GNT3 expression is associated with pelvic lymph node metastasis and poor outcome in early-stage cervical cancer patients. B3GNT3 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer. |
doi_str_mv | 10.1371/journal.pone.0144360 |
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The mRNA and protein levels of B3GNT3 expression were examined in eight cervical cancer cell lines and ten paired cervical cancer tumors, using real-time PCR and western blotting, respectively. Immunohistochemistry (IHC) was used to analyze B3GNT3 protein expression in paraffin-embedded tissues from 196 early-stage cervical cancer patients. Statistical analyses were applied to evaluate the association between B3GNT3 expression scores and clinical parameters, as well as patient survival.
B3GNT3 expression was significantly upregulated in cervical cancer cell lines and lesions compared with normal cells and adjacent noncancerous cervical tissues. In the 196 cases of tested early-stage cervical cancer samples, the B3GNT3 protein level was positively correlated with high risk TYPES of human papillomavirus (HPV) infection (P = 0.026), FIGO stage (P < 0.001), tumor size (P = 0.025), tumor recurrence (P = 0.004), vital status (P < 0.001), concurrent chemotherapy and radiotherapy (P = 0.016), lymphovascular space involvement (P = 0.003) and most importantly, lymph node metastasis (P = 0.003). Patients with high B3GNT3 expression had a shorter overall survival (OS) and disease-free survival (DFS) compared with those with low expression of this protein. Multivariate analysis suggested that B3GNT3 expression is an independent prognostic indicator for cervical cancer patients.
Our study demonstrated that elevated B3GNT3 expression is associated with pelvic lymph node metastasis and poor outcome in early-stage cervical cancer patients. B3GNT3 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0144360</identifier><identifier>PMID: 26709519</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antigens ; Apoptosis ; Biomarkers ; Biomarkers, Tumor - biosynthesis ; Biomarkers, Tumor - metabolism ; Biosynthesis ; Biotechnology ; Cancer ; Cancer therapies ; Cell Line, Tumor ; Cell survival ; Cervical cancer ; Cervix ; Chemotherapy ; Clinical outcomes ; Collaboration ; Colorectal cancer ; Development and progression ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Ethics ; Female ; Gene expression ; Genetic aspects ; HeLa Cells ; Homing ; Human papillomavirus ; Humans ; Immunohistochemistry ; L-selectin ; L-Selectin - biosynthesis ; Laboratories ; Lesions ; Ligands ; Lymph ; Lymph nodes ; Lymph Nodes - pathology ; Lymphatic metastasis ; Lymphatic Metastasis - genetics ; Lymphatic system ; Lymphocytes ; Medical prognosis ; Medical screening ; Medicine ; Metastases ; Metastasis ; Middle Aged ; mRNA ; Multivariate analysis ; N-Acetylglucosaminyltransferases - biosynthesis ; N-Acetylglucosaminyltransferases - genetics ; N-Acetylglucosinyldiphosphodolichol N-acetylglucosaminyltransferase ; Neoplasm Staging ; Oncology ; Paraffin ; Patients ; Physiological aspects ; Prognosis ; Proteins ; Radiation therapy ; Real-Time Polymerase Chain Reaction ; RNA, Messenger - biosynthesis ; Squamous cell carcinoma ; Statistical analysis ; Statistical methods ; Survival ; Tissues ; Tumor cell lines ; Tumors ; Uterine Cervical Neoplasms - mortality ; Uterine Cervical Neoplasms - pathology ; Western blotting</subject><ispartof>PloS one, 2015-12, Vol.10 (12), p.e0144360-e0144360</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Zhang et al 2015 Zhang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-5e95fa257f73cc0210de2dda7d58d3ab499b7d33c0c5feecd22c4860533fa9f13</citedby><cites>FETCH-LOGICAL-c692t-5e95fa257f73cc0210de2dda7d58d3ab499b7d33c0c5feecd22c4860533fa9f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692472/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692472/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26709519$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Weijing</creatorcontrib><creatorcontrib>Hou, Teng</creatorcontrib><creatorcontrib>Niu, Chunhao</creatorcontrib><creatorcontrib>Song, Libing</creatorcontrib><creatorcontrib>Zhang, Yanna</creatorcontrib><title>B3GNT3 Expression Is a Novel Marker Correlated with Pelvic Lymph Node Metastasis and Poor Clinical Outcome in Early-Stage Cervical Cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The β1,3-N-acetylglucosaminyltransferase-3 gene (B3GNT3) encodes a member of the B3GNT family that functions as the backbone structure of dimeric sialyl-Lewis A and is involved in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. B3GNT3 has been implicated as an important element in the development of certain cancers. However, the characteristics of B3GNT3 in the development and progression of cancer remain largely unknown. Thus, our study aimed to investigate the expression pattern and the prognostic value of B3GNT3 in patients with early-stage cervical cancer.
The mRNA and protein levels of B3GNT3 expression were examined in eight cervical cancer cell lines and ten paired cervical cancer tumors, using real-time PCR and western blotting, respectively. Immunohistochemistry (IHC) was used to analyze B3GNT3 protein expression in paraffin-embedded tissues from 196 early-stage cervical cancer patients. Statistical analyses were applied to evaluate the association between B3GNT3 expression scores and clinical parameters, as well as patient survival.
B3GNT3 expression was significantly upregulated in cervical cancer cell lines and lesions compared with normal cells and adjacent noncancerous cervical tissues. In the 196 cases of tested early-stage cervical cancer samples, the B3GNT3 protein level was positively correlated with high risk TYPES of human papillomavirus (HPV) infection (P = 0.026), FIGO stage (P < 0.001), tumor size (P = 0.025), tumor recurrence (P = 0.004), vital status (P < 0.001), concurrent chemotherapy and radiotherapy (P = 0.016), lymphovascular space involvement (P = 0.003) and most importantly, lymph node metastasis (P = 0.003). Patients with high B3GNT3 expression had a shorter overall survival (OS) and disease-free survival (DFS) compared with those with low expression of this protein. Multivariate analysis suggested that B3GNT3 expression is an independent prognostic indicator for cervical cancer patients.
Our study demonstrated that elevated B3GNT3 expression is associated with pelvic lymph node metastasis and poor outcome in early-stage cervical cancer patients. B3GNT3 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer.</description><subject>Antigens</subject><subject>Apoptosis</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - biosynthesis</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Biosynthesis</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Cell survival</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Chemotherapy</subject><subject>Clinical outcomes</subject><subject>Collaboration</subject><subject>Colorectal cancer</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Disease Progression</subject><subject>Disease-Free Survival</subject><subject>Ethics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>HeLa Cells</subject><subject>Homing</subject><subject>Human papillomavirus</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>L-selectin</subject><subject>L-Selectin - biosynthesis</subject><subject>Laboratories</subject><subject>Lesions</subject><subject>Ligands</subject><subject>Lymph</subject><subject>Lymph nodes</subject><subject>Lymph Nodes - pathology</subject><subject>Lymphatic metastasis</subject><subject>Lymphatic Metastasis - genetics</subject><subject>Lymphatic system</subject><subject>Lymphocytes</subject><subject>Medical prognosis</subject><subject>Medical screening</subject><subject>Medicine</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>mRNA</subject><subject>Multivariate analysis</subject><subject>N-Acetylglucosaminyltransferases - biosynthesis</subject><subject>N-Acetylglucosaminyltransferases - genetics</subject><subject>N-Acetylglucosinyldiphosphodolichol N-acetylglucosaminyltransferase</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Paraffin</subject><subject>Patients</subject><subject>Physiological aspects</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Radiation therapy</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Squamous cell carcinoma</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Survival</subject><subject>Tissues</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><subject>Uterine Cervical Neoplasms - mortality</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Western blotting</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tuEzEQhlcIREvhDRBYQkJwkeDDeg83lUoUSqT0IFq4tRx7NnFx1sH2huYReGucJq0S1Au0lnZlf_8_O-OZLHtNcJ-wkny6cZ1vpe0vXAt9TPKcFfhJdkhqRnsFxezpzvdB9iKEG4w5q4rieXZAixLXnNSH2Z_P7PT8mqHh7cJDCMa1aBSQROduCRadSf8TPBo478HKCBr9NnGGLsEujULj1XwxS6QGdAZRhrRM0rYaXTqXVNa0RkmLLrqo3ByQadFQervqXUU5BTQAv7w7H8hWgX-ZPWukDfBq-z7Kvn8ZXg--9sYXp6PBybiniprGHoeaN5LysimZUpgSrIFqLUvNK83kJK_rSakZU1jxBkBpSlVeFSl11si6Iewoe7vxXVgXxLaKQZCSU1JhWuWJGG0I7eSNWHgzl34lnDTibsP5qZA-GmVBsHzCNTBS0prmudZ1yZu6kGWBgVQKdPI63kbrJnPQCtropd0z3T9pzUxM3VLkKdu8pMngw9bAu18dhCjmJiiwVrbgus1_84rXBU_ou3_Qx7PbUlOZEjBt41JctTYVJ3nqD1xgsg7bf4RKj4a5UanlGpP29wQf9wSJiXAbp7ILQYyuvv0_e_Fjn32_w85A2jgLznYxtWrYB_MNqLwLwUPzUGSCxXpi7qsh1hMjthOTZG92L-hBdD8i7C_PTBBY</recordid><startdate>20151228</startdate><enddate>20151228</enddate><creator>Zhang, Weijing</creator><creator>Hou, Teng</creator><creator>Niu, Chunhao</creator><creator>Song, Libing</creator><creator>Zhang, Yanna</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20151228</creationdate><title>B3GNT3 Expression Is a Novel Marker Correlated with Pelvic Lymph Node Metastasis and Poor Clinical Outcome in Early-Stage Cervical Cancer</title><author>Zhang, Weijing ; Hou, Teng ; Niu, Chunhao ; Song, Libing ; Zhang, Yanna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-5e95fa257f73cc0210de2dda7d58d3ab499b7d33c0c5feecd22c4860533fa9f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Antigens</topic><topic>Apoptosis</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - biosynthesis</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Biosynthesis</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell Line, Tumor</topic><topic>Cell survival</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>Chemotherapy</topic><topic>Clinical outcomes</topic><topic>Collaboration</topic><topic>Colorectal cancer</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Disease Progression</topic><topic>Disease-Free Survival</topic><topic>Ethics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>HeLa Cells</topic><topic>Homing</topic><topic>Human papillomavirus</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>L-selectin</topic><topic>L-Selectin - biosynthesis</topic><topic>Laboratories</topic><topic>Lesions</topic><topic>Ligands</topic><topic>Lymph</topic><topic>Lymph nodes</topic><topic>Lymph Nodes - pathology</topic><topic>Lymphatic metastasis</topic><topic>Lymphatic Metastasis - genetics</topic><topic>Lymphatic system</topic><topic>Lymphocytes</topic><topic>Medical prognosis</topic><topic>Medical screening</topic><topic>Medicine</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>mRNA</topic><topic>Multivariate analysis</topic><topic>N-Acetylglucosaminyltransferases - biosynthesis</topic><topic>N-Acetylglucosaminyltransferases - genetics</topic><topic>N-Acetylglucosinyldiphosphodolichol N-acetylglucosaminyltransferase</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Paraffin</topic><topic>Patients</topic><topic>Physiological aspects</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Radiation therapy</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Squamous cell carcinoma</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Survival</topic><topic>Tissues</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><topic>Uterine Cervical Neoplasms - mortality</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Weijing</creatorcontrib><creatorcontrib>Hou, Teng</creatorcontrib><creatorcontrib>Niu, Chunhao</creatorcontrib><creatorcontrib>Song, Libing</creatorcontrib><creatorcontrib>Zhang, Yanna</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Weijing</au><au>Hou, Teng</au><au>Niu, Chunhao</au><au>Song, Libing</au><au>Zhang, Yanna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>B3GNT3 Expression Is a Novel Marker Correlated with Pelvic Lymph Node Metastasis and Poor Clinical Outcome in Early-Stage Cervical Cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-12-28</date><risdate>2015</risdate><volume>10</volume><issue>12</issue><spage>e0144360</spage><epage>e0144360</epage><pages>e0144360-e0144360</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The β1,3-N-acetylglucosaminyltransferase-3 gene (B3GNT3) encodes a member of the B3GNT family that functions as the backbone structure of dimeric sialyl-Lewis A and is involved in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. B3GNT3 has been implicated as an important element in the development of certain cancers. However, the characteristics of B3GNT3 in the development and progression of cancer remain largely unknown. Thus, our study aimed to investigate the expression pattern and the prognostic value of B3GNT3 in patients with early-stage cervical cancer.
The mRNA and protein levels of B3GNT3 expression were examined in eight cervical cancer cell lines and ten paired cervical cancer tumors, using real-time PCR and western blotting, respectively. Immunohistochemistry (IHC) was used to analyze B3GNT3 protein expression in paraffin-embedded tissues from 196 early-stage cervical cancer patients. Statistical analyses were applied to evaluate the association between B3GNT3 expression scores and clinical parameters, as well as patient survival.
B3GNT3 expression was significantly upregulated in cervical cancer cell lines and lesions compared with normal cells and adjacent noncancerous cervical tissues. In the 196 cases of tested early-stage cervical cancer samples, the B3GNT3 protein level was positively correlated with high risk TYPES of human papillomavirus (HPV) infection (P = 0.026), FIGO stage (P < 0.001), tumor size (P = 0.025), tumor recurrence (P = 0.004), vital status (P < 0.001), concurrent chemotherapy and radiotherapy (P = 0.016), lymphovascular space involvement (P = 0.003) and most importantly, lymph node metastasis (P = 0.003). Patients with high B3GNT3 expression had a shorter overall survival (OS) and disease-free survival (DFS) compared with those with low expression of this protein. Multivariate analysis suggested that B3GNT3 expression is an independent prognostic indicator for cervical cancer patients.
Our study demonstrated that elevated B3GNT3 expression is associated with pelvic lymph node metastasis and poor outcome in early-stage cervical cancer patients. B3GNT3 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26709519</pmid><doi>10.1371/journal.pone.0144360</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2015-12, Vol.10 (12), p.e0144360-e0144360 |
issn | 1932-6203 1932-6203 |
language | eng |
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source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
subjects | Antigens Apoptosis Biomarkers Biomarkers, Tumor - biosynthesis Biomarkers, Tumor - metabolism Biosynthesis Biotechnology Cancer Cancer therapies Cell Line, Tumor Cell survival Cervical cancer Cervix Chemotherapy Clinical outcomes Collaboration Colorectal cancer Development and progression Diagnosis Disease Progression Disease-Free Survival Ethics Female Gene expression Genetic aspects HeLa Cells Homing Human papillomavirus Humans Immunohistochemistry L-selectin L-Selectin - biosynthesis Laboratories Lesions Ligands Lymph Lymph nodes Lymph Nodes - pathology Lymphatic metastasis Lymphatic Metastasis - genetics Lymphatic system Lymphocytes Medical prognosis Medical screening Medicine Metastases Metastasis Middle Aged mRNA Multivariate analysis N-Acetylglucosaminyltransferases - biosynthesis N-Acetylglucosaminyltransferases - genetics N-Acetylglucosinyldiphosphodolichol N-acetylglucosaminyltransferase Neoplasm Staging Oncology Paraffin Patients Physiological aspects Prognosis Proteins Radiation therapy Real-Time Polymerase Chain Reaction RNA, Messenger - biosynthesis Squamous cell carcinoma Statistical analysis Statistical methods Survival Tissues Tumor cell lines Tumors Uterine Cervical Neoplasms - mortality Uterine Cervical Neoplasms - pathology Western blotting |
title | B3GNT3 Expression Is a Novel Marker Correlated with Pelvic Lymph Node Metastasis and Poor Clinical Outcome in Early-Stage Cervical Cancer |
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