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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Veröffentlicht in:PloS one 2015-12, Vol.10 (12), p.e0144360-e0144360
Hauptverfasser: Zhang, Weijing, Hou, Teng, Niu, Chunhao, Song, Libing, Zhang, Yanna
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Hou, Teng
Niu, Chunhao
Song, Libing
Zhang, Yanna
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.
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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 &lt; 0.001), tumor size (P = 0.025), tumor recurrence (P = 0.004), vital status (P &lt; 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. 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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 &lt; 0.001), tumor size (P = 0.025), tumor recurrence (P = 0.004), vital status (P &lt; 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 - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - 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 &lt; 0.001), tumor size (P = 0.025), tumor recurrence (P = 0.004), vital status (P &lt; 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>
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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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