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HIPK2 Overexpression and Its Prognostic Role in Human Papillomavirus-Positive Tonsillar Squamous Cell Carcinoma
Tonsillar squamous cell carcinomas (TSCCs) are the most common human papillomavirus- (HPV-) associated oropharyngeal cancers with poor prognosis. Homeodomain-interacting protein kinase 2 (HIPK2) is a central regulator of p53, which participates in apoptosis during the DNA damage response. HIPK2 is i...
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| Published in: | BioMed research international 2017-01, Vol.2017 (2017), p.1-10 |
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| creator | Cho, Seong Jin Nam, Eun Sook Kang, So Young Kwon, Mi Jung Rho, Young-Soo |
| description | Tonsillar squamous cell carcinomas (TSCCs) are the most common human papillomavirus- (HPV-) associated oropharyngeal cancers with poor prognosis. Homeodomain-interacting protein kinase 2 (HIPK2) is a central regulator of p53, which participates in apoptosis during the DNA damage response. HIPK2 is involved in HPV-associated uterine cervical and cutaneous carcinogenesis through its binding of HPV E6, thereby preventing apoptosis and contributing to tumor progression. However, its clinical and prognostic significance in TSCC remains unclear. HIPK2 mRNA levels were analyzed in 20 normal tonsils and 20 TSCC specimens using real-time reverse transcription polymerase chain reaction. Immunohistochemistry of HIPK2 was performed in 79 resected specimens. HIPK2 was expressed in 57% of the TSCCs, and HIPK2 protein expression and HIPK2 mRNA levels were higher in TSCCs than in normal tonsils. HIPK2 overexpression was associated with poorly differentiated carcinoma and low alcohol consumption and was an independent prognostic factor for overall survival and disease-free survival (DFS) in TSCC and a negative independent prognostic factor for DFS in patients receiving postoperative radiotherapy. HIPK2 overexpression had a significant association with poorer DFS in HPV-positive TSCCs, but not in HPV-negative tumors. HIPK2 overexpression may be a potential prognostic marker for predicting prognoses and a high risk of recurrence, particularly in patients with HPV-positive TSCC. |
| doi_str_mv | 10.1155/2017/1056427 |
| format | article |
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Homeodomain-interacting protein kinase 2 (HIPK2) is a central regulator of p53, which participates in apoptosis during the DNA damage response. HIPK2 is involved in HPV-associated uterine cervical and cutaneous carcinogenesis through its binding of HPV E6, thereby preventing apoptosis and contributing to tumor progression. However, its clinical and prognostic significance in TSCC remains unclear. HIPK2 mRNA levels were analyzed in 20 normal tonsils and 20 TSCC specimens using real-time reverse transcription polymerase chain reaction. Immunohistochemistry of HIPK2 was performed in 79 resected specimens. HIPK2 was expressed in 57% of the TSCCs, and HIPK2 protein expression and HIPK2 mRNA levels were higher in TSCCs than in normal tonsils. HIPK2 overexpression was associated with poorly differentiated carcinoma and low alcohol consumption and was an independent prognostic factor for overall survival and disease-free survival (DFS) in TSCC and a negative independent prognostic factor for DFS in patients receiving postoperative radiotherapy. HIPK2 overexpression had a significant association with poorer DFS in HPV-positive TSCCs, but not in HPV-negative tumors. HIPK2 overexpression may be a potential prognostic marker for predicting prognoses and a high risk of recurrence, particularly in patients with HPV-positive TSCC.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2017/1056427</identifier><identifier>PMID: 28607924</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Aged ; Alcohol ; Analysis ; Apoptosis ; Biomarkers, Tumor - genetics ; Cancer therapies ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - virology ; Carrier Proteins - genetics ; Cervical cancer ; Chemotherapy ; Development and progression ; Disease-Free Survival ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Head & neck cancer ; Health aspects ; Hospitals ; Human papillomavirus ; Humans ; Infections ; Kinases ; Male ; Medical prognosis ; Medical records ; Medicine ; Middle Aged ; Otolaryngology ; Papillomaviridae - genetics ; Papillomaviridae - pathogenicity ; Papillomavirus Infections - genetics ; Papillomavirus Infections - virology ; Papillomaviruses ; Pathology ; Phosphorylation ; Prognosis ; Protein expression ; Protein kinases ; Protein-Serine-Threonine Kinases - genetics ; Proteins ; Radiation therapy ; RNA, Messenger - genetics ; Signal transduction ; Squamous cell carcinoma ; Studies ; Surgery ; Throat cancer ; Thyroid gland ; Tonsillar Neoplasms - genetics ; Tonsillar Neoplasms - pathology ; Tonsillar Neoplasms - virology ; Tumor Suppressor Protein p53 - genetics ; Tumors ; University colleges</subject><ispartof>BioMed research international, 2017-01, Vol.2017 (2017), p.1-10</ispartof><rights>Copyright © 2017 Mi Jung Kwon et al.</rights><rights>COPYRIGHT 2017 John Wiley & Sons, Inc.</rights><rights>Copyright © 2017 Mi Jung Kwon et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2017 Mi Jung Kwon et al. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c565t-2f10ef852afb226157a209bf2b303f53724ca17cea298e9ad86695697a99615c3</citedby><cites>FETCH-LOGICAL-c565t-2f10ef852afb226157a209bf2b303f53724ca17cea298e9ad86695697a99615c3</cites><orcidid>0000-0002-2441-0448</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1906058665/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1906058665?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,25753,27924,27925,37012,37013,44590,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28607924$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Prigent, Claude</contributor><creatorcontrib>Cho, Seong Jin</creatorcontrib><creatorcontrib>Nam, Eun Sook</creatorcontrib><creatorcontrib>Kang, So Young</creatorcontrib><creatorcontrib>Kwon, Mi Jung</creatorcontrib><creatorcontrib>Rho, Young-Soo</creatorcontrib><title>HIPK2 Overexpression and Its Prognostic Role in Human Papillomavirus-Positive Tonsillar Squamous Cell Carcinoma</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Tonsillar squamous cell carcinomas (TSCCs) are the most common human papillomavirus- (HPV-) associated oropharyngeal cancers with poor prognosis. Homeodomain-interacting protein kinase 2 (HIPK2) is a central regulator of p53, which participates in apoptosis during the DNA damage response. HIPK2 is involved in HPV-associated uterine cervical and cutaneous carcinogenesis through its binding of HPV E6, thereby preventing apoptosis and contributing to tumor progression. However, its clinical and prognostic significance in TSCC remains unclear. HIPK2 mRNA levels were analyzed in 20 normal tonsils and 20 TSCC specimens using real-time reverse transcription polymerase chain reaction. Immunohistochemistry of HIPK2 was performed in 79 resected specimens. HIPK2 was expressed in 57% of the TSCCs, and HIPK2 protein expression and HIPK2 mRNA levels were higher in TSCCs than in normal tonsils. HIPK2 overexpression was associated with poorly differentiated carcinoma and low alcohol consumption and was an independent prognostic factor for overall survival and disease-free survival (DFS) in TSCC and a negative independent prognostic factor for DFS in patients receiving postoperative radiotherapy. HIPK2 overexpression had a significant association with poorer DFS in HPV-positive TSCCs, but not in HPV-negative tumors. HIPK2 overexpression may be a potential prognostic marker for predicting prognoses and a high risk of recurrence, particularly in patients with HPV-positive TSCC.</description><subject>Aged</subject><subject>Alcohol</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer therapies</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - virology</subject><subject>Carrier Proteins - genetics</subject><subject>Cervical cancer</subject><subject>Chemotherapy</subject><subject>Development and progression</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Head & neck cancer</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Human papillomavirus</subject><subject>Humans</subject><subject>Infections</subject><subject>Kinases</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical records</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Otolaryngology</subject><subject>Papillomaviridae - 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Homeodomain-interacting protein kinase 2 (HIPK2) is a central regulator of p53, which participates in apoptosis during the DNA damage response. HIPK2 is involved in HPV-associated uterine cervical and cutaneous carcinogenesis through its binding of HPV E6, thereby preventing apoptosis and contributing to tumor progression. However, its clinical and prognostic significance in TSCC remains unclear. HIPK2 mRNA levels were analyzed in 20 normal tonsils and 20 TSCC specimens using real-time reverse transcription polymerase chain reaction. Immunohistochemistry of HIPK2 was performed in 79 resected specimens. HIPK2 was expressed in 57% of the TSCCs, and HIPK2 protein expression and HIPK2 mRNA levels were higher in TSCCs than in normal tonsils. HIPK2 overexpression was associated with poorly differentiated carcinoma and low alcohol consumption and was an independent prognostic factor for overall survival and disease-free survival (DFS) in TSCC and a negative independent prognostic factor for DFS in patients receiving postoperative radiotherapy. HIPK2 overexpression had a significant association with poorer DFS in HPV-positive TSCCs, but not in HPV-negative tumors. HIPK2 overexpression may be a potential prognostic marker for predicting prognoses and a high risk of recurrence, particularly in patients with HPV-positive TSCC.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>28607924</pmid><doi>10.1155/2017/1056427</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-2441-0448</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Alcohol Analysis Apoptosis Biomarkers, Tumor - genetics Cancer therapies Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - virology Carrier Proteins - genetics Cervical cancer Chemotherapy Development and progression Disease-Free Survival Female Gene expression Gene Expression Regulation, Neoplastic Genetic aspects Head & neck cancer Health aspects Hospitals Human papillomavirus Humans Infections Kinases Male Medical prognosis Medical records Medicine Middle Aged Otolaryngology Papillomaviridae - genetics Papillomaviridae - pathogenicity Papillomavirus Infections - genetics Papillomavirus Infections - virology Papillomaviruses Pathology Phosphorylation Prognosis Protein expression Protein kinases Protein-Serine-Threonine Kinases - genetics Proteins Radiation therapy RNA, Messenger - genetics Signal transduction Squamous cell carcinoma Studies Surgery Throat cancer Thyroid gland Tonsillar Neoplasms - genetics Tonsillar Neoplasms - pathology Tonsillar Neoplasms - virology Tumor Suppressor Protein p53 - genetics Tumors University colleges |
| title | HIPK2 Overexpression and Its Prognostic Role in Human Papillomavirus-Positive Tonsillar Squamous Cell Carcinoma |
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