Circulating free DNA integrity index and promoter methylation of tumor suppressor gene P16, DAPK and RASSF1A as a biomarker for oropharyngeal squamous cell carcinoma
Circulating free DNA (cfDNA) is in use for the non-invasive diagnosis of tumors. Methylation of tumor suppressor genes (TSGs) is an early event in carcinogenesis and may serve as tumor biomarker. We have investigated cfDNA integrity and methylation of tumor suppressor genes P16, DAPK and RASSF1A in...
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| Veröffentlicht in: | Pathology, research and practice research and practice, 2023-06, Vol.246, p.154489-154489, Article 154489 |
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| creator | Kumari, Swati Mishra, Sridhar Anand, Nidhi Hadi, Rahat Rastogi, Madhup Husain, Nuzhat |
| description | Circulating free DNA (cfDNA) is in use for the non-invasive diagnosis of tumors. Methylation of tumor suppressor genes (TSGs) is an early event in carcinogenesis and may serve as tumor biomarker. We have investigated cfDNA integrity and methylation of tumor suppressor genes P16, DAPK and RASSF1A in serum cfDNA of oropharyngeal squamous cell carcinoma (OPSCC) comparing paired serum and tumor tissue samples to evaluate their diagnostic use. Prospective case-control study, paired serum and tissue samples from 56 OPSCC, and 15 normal controls (NC). Sybr green Quantitate real time PCR was used for cfDNA quantification through amplification ALU 115 and 247 fragments. Promoter methylation of was analyzed in paired samples using methylation specific PCR. There was significantly high cfDNA integrity in OPSCC compared to normal control (p = |
| doi_str_mv | 10.1016/j.prp.2023.154489 |
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Methylation of tumor suppressor genes (TSGs) is an early event in carcinogenesis and may serve as tumor biomarker. We have investigated cfDNA integrity and methylation of tumor suppressor genes P16, DAPK and RASSF1A in serum cfDNA of oropharyngeal squamous cell carcinoma (OPSCC) comparing paired serum and tumor tissue samples to evaluate their diagnostic use. Prospective case-control study, paired serum and tissue samples from 56 OPSCC, and 15 normal controls (NC). Sybr green Quantitate real time PCR was used for cfDNA quantification through amplification ALU 115 and 247 fragments. Promoter methylation of was analyzed in paired samples using methylation specific PCR. There was significantly high cfDNA integrity in OPSCC compared to normal control (p = < 0.0001). The cfDNA integrity values were significantly higher and associated with nodal status (p = 0.016). The AUC for cfDNA integrity was 0.967. The P16, DAPK and RASSF1 promoters were significantly hypermethylated in serum of OPSCC compared to NC with high concordance in tissue (up to 96.55 %). The gene promoter methylation of P16 was associated with smoking (p = 0.030), RASSF1A with stage (p = 0.011). The combination of ALU115 with cfDNA integrity and combination of gene methylation increases diagnostic sensitivity. In followup samples the cfDNA change was not different. Liquid biopsy approach including cfDNA integrity, methylation profiling in cfDNA, in combination or separately can assist in the diagnosis of OPSCC along with radio diagnostic scan. Serum changes represent changes in tissue with very high concordance.</description><identifier>ISSN: 0344-0338</identifier><identifier>EISSN: 1618-0631</identifier><identifier>DOI: 10.1016/j.prp.2023.154489</identifier><identifier>PMID: 37150134</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Biomarkers, Tumor - genetics ; Case-Control Studies ; Cell-Free Nucleic Acids ; CfDNA integrity ; Circulating free DNA ; DNA Methylation ; Genes, Tumor Suppressor ; Head and Neck Neoplasms - genetics ; Humans ; Liquid biopsy ; Oropharyngeal cancer ; Promoter methylation ; Squamous Cell Carcinoma of Head and Neck - genetics ; Tumor suppressor genes</subject><ispartof>Pathology, research and practice, 2023-06, Vol.246, p.154489-154489, Article 154489</ispartof><rights>2023</rights><rights>Copyright © 2023. Published by Elsevier GmbH.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-1e72a72a31aa1f6d31091f6d76527313600716695b5d4255faa7d8c3e66e7cb13</citedby><cites>FETCH-LOGICAL-c353t-1e72a72a31aa1f6d31091f6d76527313600716695b5d4255faa7d8c3e66e7cb13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0344033823001899$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37150134$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kumari, Swati</creatorcontrib><creatorcontrib>Mishra, Sridhar</creatorcontrib><creatorcontrib>Anand, Nidhi</creatorcontrib><creatorcontrib>Hadi, Rahat</creatorcontrib><creatorcontrib>Rastogi, Madhup</creatorcontrib><creatorcontrib>Husain, Nuzhat</creatorcontrib><title>Circulating free DNA integrity index and promoter methylation of tumor suppressor gene P16, DAPK and RASSF1A as a biomarker for oropharyngeal squamous cell carcinoma</title><title>Pathology, research and practice</title><addtitle>Pathol Res Pract</addtitle><description>Circulating free DNA (cfDNA) is in use for the non-invasive diagnosis of tumors. Methylation of tumor suppressor genes (TSGs) is an early event in carcinogenesis and may serve as tumor biomarker. We have investigated cfDNA integrity and methylation of tumor suppressor genes P16, DAPK and RASSF1A in serum cfDNA of oropharyngeal squamous cell carcinoma (OPSCC) comparing paired serum and tumor tissue samples to evaluate their diagnostic use. Prospective case-control study, paired serum and tissue samples from 56 OPSCC, and 15 normal controls (NC). Sybr green Quantitate real time PCR was used for cfDNA quantification through amplification ALU 115 and 247 fragments. Promoter methylation of was analyzed in paired samples using methylation specific PCR. There was significantly high cfDNA integrity in OPSCC compared to normal control (p = < 0.0001). The cfDNA integrity values were significantly higher and associated with nodal status (p = 0.016). The AUC for cfDNA integrity was 0.967. The P16, DAPK and RASSF1 promoters were significantly hypermethylated in serum of OPSCC compared to NC with high concordance in tissue (up to 96.55 %). The gene promoter methylation of P16 was associated with smoking (p = 0.030), RASSF1A with stage (p = 0.011). The combination of ALU115 with cfDNA integrity and combination of gene methylation increases diagnostic sensitivity. In followup samples the cfDNA change was not different. Liquid biopsy approach including cfDNA integrity, methylation profiling in cfDNA, in combination or separately can assist in the diagnosis of OPSCC along with radio diagnostic scan. Serum changes represent changes in tissue with very high concordance.</description><subject>Biomarkers, Tumor - genetics</subject><subject>Case-Control Studies</subject><subject>Cell-Free Nucleic Acids</subject><subject>CfDNA integrity</subject><subject>Circulating free DNA</subject><subject>DNA Methylation</subject><subject>Genes, Tumor Suppressor</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Humans</subject><subject>Liquid biopsy</subject><subject>Oropharyngeal cancer</subject><subject>Promoter methylation</subject><subject>Squamous Cell Carcinoma of Head and Neck - genetics</subject><subject>Tumor suppressor genes</subject><issn>0344-0338</issn><issn>1618-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFu1DAQhi0EokvhAbggHzmQxRPHTlacoi0FRAUVhbPldSZbL4md2g5iH4j3xGELRyRLMxp9_68Z_4Q8B7YGBvL1YT2FaV2ykq9BVFWzeUBWIKEpmOTwkKwYr6qCcd6ckScxHhhjNavgMTnjNQgGvFqRX1sbzDzoZN2e9gGRXnxqqXUJ98GmY-46_Em16-gU_OgTBjpiuj0uCu-o72maRx9onKcpYIy53aNDeg3yFb1orz_-0X5pb24uoaU6Uk131o86fM9OfaZ98NOtDke3Rz3QeDfr0c-RGhwGanQw1mX6KXnU6yHis_t6Tr5dvv26fV9cfX73YdteFYYLngrAutT5cdAaetlxYJul1lKUNQcu8weAlBuxE11VCtFrXXeN4Sgl1mYH_Jy8PPnmY-9mjEmNNi6raId5K1U2ACUILkVG4YSa4GMM2Ksp2HzXUQFTSzrqkCeTWtJRp3Sy5sW9_bwbsfun-BtHBt6cAMxH_rAYVDQWncHOBjRJdd7-x_43Sp-grA</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Kumari, Swati</creator><creator>Mishra, Sridhar</creator><creator>Anand, Nidhi</creator><creator>Hadi, Rahat</creator><creator>Rastogi, Madhup</creator><creator>Husain, Nuzhat</creator><general>Elsevier GmbH</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>7X8</scope></search><sort><creationdate>202306</creationdate><title>Circulating free DNA integrity index and promoter methylation of tumor suppressor gene P16, DAPK and RASSF1A as a biomarker for oropharyngeal squamous cell carcinoma</title><author>Kumari, Swati ; Mishra, Sridhar ; Anand, Nidhi ; Hadi, Rahat ; Rastogi, Madhup ; Husain, Nuzhat</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-1e72a72a31aa1f6d31091f6d76527313600716695b5d4255faa7d8c3e66e7cb13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Biomarkers, Tumor - genetics</topic><topic>Case-Control Studies</topic><topic>Cell-Free Nucleic Acids</topic><topic>CfDNA integrity</topic><topic>Circulating free DNA</topic><topic>DNA Methylation</topic><topic>Genes, Tumor Suppressor</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Humans</topic><topic>Liquid biopsy</topic><topic>Oropharyngeal cancer</topic><topic>Promoter methylation</topic><topic>Squamous Cell Carcinoma of Head and Neck - genetics</topic><topic>Tumor suppressor genes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kumari, Swati</creatorcontrib><creatorcontrib>Mishra, Sridhar</creatorcontrib><creatorcontrib>Anand, Nidhi</creatorcontrib><creatorcontrib>Hadi, Rahat</creatorcontrib><creatorcontrib>Rastogi, Madhup</creatorcontrib><creatorcontrib>Husain, Nuzhat</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pathology, research and practice</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kumari, Swati</au><au>Mishra, Sridhar</au><au>Anand, Nidhi</au><au>Hadi, Rahat</au><au>Rastogi, Madhup</au><au>Husain, Nuzhat</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating free DNA integrity index and promoter methylation of tumor suppressor gene P16, DAPK and RASSF1A as a biomarker for oropharyngeal squamous cell carcinoma</atitle><jtitle>Pathology, research and practice</jtitle><addtitle>Pathol Res Pract</addtitle><date>2023-06</date><risdate>2023</risdate><volume>246</volume><spage>154489</spage><epage>154489</epage><pages>154489-154489</pages><artnum>154489</artnum><issn>0344-0338</issn><eissn>1618-0631</eissn><abstract>Circulating free DNA (cfDNA) is in use for the non-invasive diagnosis of tumors. Methylation of tumor suppressor genes (TSGs) is an early event in carcinogenesis and may serve as tumor biomarker. We have investigated cfDNA integrity and methylation of tumor suppressor genes P16, DAPK and RASSF1A in serum cfDNA of oropharyngeal squamous cell carcinoma (OPSCC) comparing paired serum and tumor tissue samples to evaluate their diagnostic use. Prospective case-control study, paired serum and tissue samples from 56 OPSCC, and 15 normal controls (NC). Sybr green Quantitate real time PCR was used for cfDNA quantification through amplification ALU 115 and 247 fragments. Promoter methylation of was analyzed in paired samples using methylation specific PCR. There was significantly high cfDNA integrity in OPSCC compared to normal control (p = < 0.0001). The cfDNA integrity values were significantly higher and associated with nodal status (p = 0.016). The AUC for cfDNA integrity was 0.967. The P16, DAPK and RASSF1 promoters were significantly hypermethylated in serum of OPSCC compared to NC with high concordance in tissue (up to 96.55 %). The gene promoter methylation of P16 was associated with smoking (p = 0.030), RASSF1A with stage (p = 0.011). The combination of ALU115 with cfDNA integrity and combination of gene methylation increases diagnostic sensitivity. In followup samples the cfDNA change was not different. Liquid biopsy approach including cfDNA integrity, methylation profiling in cfDNA, in combination or separately can assist in the diagnosis of OPSCC along with radio diagnostic scan. Serum changes represent changes in tissue with very high concordance.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>37150134</pmid><doi>10.1016/j.prp.2023.154489</doi><tpages>1</tpages></addata></record> |
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| subjects | Biomarkers, Tumor - genetics Case-Control Studies Cell-Free Nucleic Acids CfDNA integrity Circulating free DNA DNA Methylation Genes, Tumor Suppressor Head and Neck Neoplasms - genetics Humans Liquid biopsy Oropharyngeal cancer Promoter methylation Squamous Cell Carcinoma of Head and Neck - genetics Tumor suppressor genes |
| title | Circulating free DNA integrity index and promoter methylation of tumor suppressor gene P16, DAPK and RASSF1A as a biomarker for oropharyngeal squamous cell carcinoma |
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