Mutually distinguishing microRNA signatures of breast, ovarian and endometrial cancers in vitro
Early diagnosis and therapy in the first stages of a malignant disease is the most crucial factor for successful cancer treatment and recovery. Currently, there is a high demand for novel diagnostic tools that indicate neoplasms in the first or pre‑malignant stages. MicroRNAs (miRNA or miR) are smal...
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creator | Hirschfeld, Marc Ge, Isabel Rücker, Gerta Waldschmidt, Julia Mayer, Sebastian Jäger, Markus Voigt, Matthias Kammerer, Bernd Nöthling, Claudia Berner, Kai Weiss, Daniela Asberger, Jasmin Erbes, Thalia |
description | Early diagnosis and therapy in the first stages of a malignant disease is the most crucial factor for successful cancer treatment and recovery. Currently, there is a high demand for novel diagnostic tools that indicate neoplasms in the first or pre‑malignant stages. MicroRNAs (miRNA or miR) are small non‑coding RNAs that may act as oncogenes and downregulate tumor‑suppressor genes. The detection and mutual discrimination of the three common female malignant neoplasia types breast (BC), ovarian (OC) and endometrial cancer (EC) could be enabled by identification of tumor entity‑specific miRNA expression differences. In the present study, the relative expression levels of 25 BC, EC and OC‑related miRNAs were assessed by reverse transcription‑quantitative PCR and determined using the 2‑ΔΔCq method for normalization against the mean of four housekeeping genes. Expression levels of all miRNAs were analyzed by regression against cell line as a factor. An expression level‑based discrimination between BC and OC cell types was obtained for a subgroup of ten different miRNA types. miR‑30 family genes, as well as three other miRNAs, were found to be uniformly upregulated in OC cells compared with BC cells. BC and EC cells could be distinguished by the expression profiles of six specific miRNAs. In addition, four miRNAs were differentially expressed between EC and OC cells. In conclusion, miRNAs were identified as a potential novel tool to detect and mutually discriminate between BC, OC and EC. Based on a subset of 25 clinically relevant human miRNA types, the present study could significantly discriminate between these three female cancer types by means of their expression levels. For further verification and validation of miRNA‑based biomarker expression signatures that enable valuable tumor detection and characterization in routine screening or potential therapy monitoring, additional and extended in vitro analyses, followed by translational studies utilizing patients' tissue and liquid biopsy materials, are required. |
doi_str_mv | 10.3892/mmr.2020.11466 |
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Currently, there is a high demand for novel diagnostic tools that indicate neoplasms in the first or pre‑malignant stages. MicroRNAs (miRNA or miR) are small non‑coding RNAs that may act as oncogenes and downregulate tumor‑suppressor genes. The detection and mutual discrimination of the three common female malignant neoplasia types breast (BC), ovarian (OC) and endometrial cancer (EC) could be enabled by identification of tumor entity‑specific miRNA expression differences. In the present study, the relative expression levels of 25 BC, EC and OC‑related miRNAs were assessed by reverse transcription‑quantitative PCR and determined using the 2‑ΔΔCq method for normalization against the mean of four housekeeping genes. Expression levels of all miRNAs were analyzed by regression against cell line as a factor. An expression level‑based discrimination between BC and OC cell types was obtained for a subgroup of ten different miRNA types. miR‑30 family genes, as well as three other miRNAs, were found to be uniformly upregulated in OC cells compared with BC cells. BC and EC cells could be distinguished by the expression profiles of six specific miRNAs. In addition, four miRNAs were differentially expressed between EC and OC cells. In conclusion, miRNAs were identified as a potential novel tool to detect and mutually discriminate between BC, OC and EC. Based on a subset of 25 clinically relevant human miRNA types, the present study could significantly discriminate between these three female cancer types by means of their expression levels. For further verification and validation of miRNA‑based biomarker expression signatures that enable valuable tumor detection and characterization in routine screening or potential therapy monitoring, additional and extended in vitro analyses, followed by translational studies utilizing patients' tissue and liquid biopsy materials, are required.</description><identifier>ISSN: 1791-2997</identifier><identifier>EISSN: 1791-3004</identifier><identifier>DOI: 10.3892/mmr.2020.11466</identifier><identifier>PMID: 33000259</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Analysis ; Biomarkers ; Biomarkers, Tumor - genetics ; Biopsy ; Breast ; Breast cancer ; Breast Neoplasms - diagnosis ; Breast Neoplasms - genetics ; Cancer diagnosis ; Cancer research ; Cancer treatment ; Cell Line, Tumor ; Diagnosis, Differential ; Early Detection of Cancer ; Endometrial cancer ; Endometrial Neoplasms - diagnosis ; Endometrial Neoplasms - genetics ; Endometrium ; Female ; Gene Expression Profiling - methods ; Gene Expression Regulation, Neoplastic ; Genes ; Genetic aspects ; Humans ; Investigations ; Kinases ; Medical diagnosis ; MicroRNA ; MicroRNAs - genetics ; miRNA ; Neoplasia ; Non-coding RNA ; Ovarian cancer ; Ovarian Neoplasms - diagnosis ; Ovarian Neoplasms - genetics ; Reverse transcription ; Scientific equipment industry ; Tumor suppressor genes</subject><ispartof>Molecular medicine reports, 2020-11, Vol.22 (5), p.4048-4060</ispartof><rights>COPYRIGHT 2020 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2020</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3456-e7ccbd0155caaa9b1226ccd78fe80519583c3561cb93372be873bffa9e5f2c4e3</citedby><cites>FETCH-LOGICAL-c3456-e7ccbd0155caaa9b1226ccd78fe80519583c3561cb93372be873bffa9e5f2c4e3</cites><orcidid>0000-0002-4796-024X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33000259$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hirschfeld, Marc</creatorcontrib><creatorcontrib>Ge, Isabel</creatorcontrib><creatorcontrib>Rücker, Gerta</creatorcontrib><creatorcontrib>Waldschmidt, Julia</creatorcontrib><creatorcontrib>Mayer, Sebastian</creatorcontrib><creatorcontrib>Jäger, Markus</creatorcontrib><creatorcontrib>Voigt, Matthias</creatorcontrib><creatorcontrib>Kammerer, Bernd</creatorcontrib><creatorcontrib>Nöthling, Claudia</creatorcontrib><creatorcontrib>Berner, Kai</creatorcontrib><creatorcontrib>Weiss, Daniela</creatorcontrib><creatorcontrib>Asberger, Jasmin</creatorcontrib><creatorcontrib>Erbes, Thalia</creatorcontrib><title>Mutually distinguishing microRNA signatures of breast, ovarian and endometrial cancers in vitro</title><title>Molecular medicine reports</title><addtitle>Mol Med Rep</addtitle><description>Early diagnosis and therapy in the first stages of a malignant disease is the most crucial factor for successful cancer treatment and recovery. Currently, there is a high demand for novel diagnostic tools that indicate neoplasms in the first or pre‑malignant stages. MicroRNAs (miRNA or miR) are small non‑coding RNAs that may act as oncogenes and downregulate tumor‑suppressor genes. The detection and mutual discrimination of the three common female malignant neoplasia types breast (BC), ovarian (OC) and endometrial cancer (EC) could be enabled by identification of tumor entity‑specific miRNA expression differences. In the present study, the relative expression levels of 25 BC, EC and OC‑related miRNAs were assessed by reverse transcription‑quantitative PCR and determined using the 2‑ΔΔCq method for normalization against the mean of four housekeeping genes. Expression levels of all miRNAs were analyzed by regression against cell line as a factor. An expression level‑based discrimination between BC and OC cell types was obtained for a subgroup of ten different miRNA types. miR‑30 family genes, as well as three other miRNAs, were found to be uniformly upregulated in OC cells compared with BC cells. BC and EC cells could be distinguished by the expression profiles of six specific miRNAs. In addition, four miRNAs were differentially expressed between EC and OC cells. In conclusion, miRNAs were identified as a potential novel tool to detect and mutually discriminate between BC, OC and EC. Based on a subset of 25 clinically relevant human miRNA types, the present study could significantly discriminate between these three female cancer types by means of their expression levels. For further verification and validation of miRNA‑based biomarker expression signatures that enable valuable tumor detection and characterization in routine screening or potential therapy monitoring, additional and extended in vitro analyses, followed by translational studies utilizing patients' tissue and liquid biopsy materials, are required.</description><subject>Analysis</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biopsy</subject><subject>Breast</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - diagnosis</subject><subject>Breast Neoplasms - genetics</subject><subject>Cancer diagnosis</subject><subject>Cancer research</subject><subject>Cancer treatment</subject><subject>Cell Line, Tumor</subject><subject>Diagnosis, Differential</subject><subject>Early Detection of Cancer</subject><subject>Endometrial cancer</subject><subject>Endometrial Neoplasms - diagnosis</subject><subject>Endometrial Neoplasms - genetics</subject><subject>Endometrium</subject><subject>Female</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Investigations</subject><subject>Kinases</subject><subject>Medical diagnosis</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Neoplasia</subject><subject>Non-coding RNA</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - diagnosis</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Reverse transcription</subject><subject>Scientific equipment industry</subject><subject>Tumor suppressor genes</subject><issn>1791-2997</issn><issn>1791-3004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkU1LHTEUhoNU1KpblxLoxkXvNR-TTLK8iP0AqyB2nWYyJ9fITGKTGcF_09_SX9Zce9tCkbM4HzzncHhfhE4oWXKl2fk45iUjjCwpbaTcQQe01XTBCWnebGumdbuP3pbyQIgUTOg9tM8rQGp5gL59mafZDsMz7kOZQlzPodzXhMfgcrq9XuES1tFOc4aCk8ddBlum9zg92RxsxDb2GGKfRphqP2Bno4NccIg_fzyFKacjtOvtUOB4mw_R1w-XdxefFlc3Hz9frK4WjjdCLqB1rusJFcJZa3VHGZPO9a3yoIigWijuuJDUdZrzlnWgWt55bzUIz1wD_BCd_b77mNP3GcpkxlAcDIONkOZiWNO0iivBSUXf_Yc-pDnH-t2GUpLQqug_am0HMCH6NGXrNkfNSnKlCBdUVmr5ClWjh6pgiuBDnb-2UOUtJYM3jzmMNj8bSszGUlMtNRtLzYuldeF0--3cjdD_xf94yH8BKo2cgw</recordid><startdate>20201101</startdate><enddate>20201101</enddate><creator>Hirschfeld, Marc</creator><creator>Ge, Isabel</creator><creator>Rücker, Gerta</creator><creator>Waldschmidt, Julia</creator><creator>Mayer, Sebastian</creator><creator>Jäger, Markus</creator><creator>Voigt, Matthias</creator><creator>Kammerer, Bernd</creator><creator>Nöthling, Claudia</creator><creator>Berner, Kai</creator><creator>Weiss, Daniela</creator><creator>Asberger, Jasmin</creator><creator>Erbes, Thalia</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</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>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4796-024X</orcidid></search><sort><creationdate>20201101</creationdate><title>Mutually distinguishing microRNA signatures of breast, ovarian and endometrial cancers in vitro</title><author>Hirschfeld, Marc ; Ge, Isabel ; Rücker, Gerta ; Waldschmidt, Julia ; Mayer, Sebastian ; Jäger, Markus ; Voigt, Matthias ; Kammerer, Bernd ; Nöthling, Claudia ; Berner, Kai ; Weiss, Daniela ; Asberger, Jasmin ; Erbes, Thalia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3456-e7ccbd0155caaa9b1226ccd78fe80519583c3561cb93372be873bffa9e5f2c4e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biopsy</topic><topic>Breast</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - diagnosis</topic><topic>Breast Neoplasms - genetics</topic><topic>Cancer diagnosis</topic><topic>Cancer research</topic><topic>Cancer treatment</topic><topic>Cell Line, Tumor</topic><topic>Diagnosis, Differential</topic><topic>Early Detection of Cancer</topic><topic>Endometrial cancer</topic><topic>Endometrial Neoplasms - diagnosis</topic><topic>Endometrial Neoplasms - genetics</topic><topic>Endometrium</topic><topic>Female</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Humans</topic><topic>Investigations</topic><topic>Kinases</topic><topic>Medical diagnosis</topic><topic>MicroRNA</topic><topic>MicroRNAs - genetics</topic><topic>miRNA</topic><topic>Neoplasia</topic><topic>Non-coding RNA</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - diagnosis</topic><topic>Ovarian Neoplasms - 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Academic</collection><jtitle>Molecular medicine reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hirschfeld, Marc</au><au>Ge, Isabel</au><au>Rücker, Gerta</au><au>Waldschmidt, Julia</au><au>Mayer, Sebastian</au><au>Jäger, Markus</au><au>Voigt, Matthias</au><au>Kammerer, Bernd</au><au>Nöthling, Claudia</au><au>Berner, Kai</au><au>Weiss, Daniela</au><au>Asberger, Jasmin</au><au>Erbes, Thalia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutually distinguishing microRNA signatures of breast, ovarian and endometrial cancers in vitro</atitle><jtitle>Molecular medicine reports</jtitle><addtitle>Mol Med Rep</addtitle><date>2020-11-01</date><risdate>2020</risdate><volume>22</volume><issue>5</issue><spage>4048</spage><epage>4060</epage><pages>4048-4060</pages><issn>1791-2997</issn><eissn>1791-3004</eissn><abstract>Early diagnosis and therapy in the first stages of a malignant disease is the most crucial factor for successful cancer treatment and recovery. Currently, there is a high demand for novel diagnostic tools that indicate neoplasms in the first or pre‑malignant stages. MicroRNAs (miRNA or miR) are small non‑coding RNAs that may act as oncogenes and downregulate tumor‑suppressor genes. The detection and mutual discrimination of the three common female malignant neoplasia types breast (BC), ovarian (OC) and endometrial cancer (EC) could be enabled by identification of tumor entity‑specific miRNA expression differences. In the present study, the relative expression levels of 25 BC, EC and OC‑related miRNAs were assessed by reverse transcription‑quantitative PCR and determined using the 2‑ΔΔCq method for normalization against the mean of four housekeeping genes. Expression levels of all miRNAs were analyzed by regression against cell line as a factor. An expression level‑based discrimination between BC and OC cell types was obtained for a subgroup of ten different miRNA types. miR‑30 family genes, as well as three other miRNAs, were found to be uniformly upregulated in OC cells compared with BC cells. BC and EC cells could be distinguished by the expression profiles of six specific miRNAs. In addition, four miRNAs were differentially expressed between EC and OC cells. In conclusion, miRNAs were identified as a potential novel tool to detect and mutually discriminate between BC, OC and EC. Based on a subset of 25 clinically relevant human miRNA types, the present study could significantly discriminate between these three female cancer types by means of their expression levels. For further verification and validation of miRNA‑based biomarker expression signatures that enable valuable tumor detection and characterization in routine screening or potential therapy monitoring, additional and extended in vitro analyses, followed by translational studies utilizing patients' tissue and liquid biopsy materials, are required.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>33000259</pmid><doi>10.3892/mmr.2020.11466</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-4796-024X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Analysis Biomarkers Biomarkers, Tumor - genetics Biopsy Breast Breast cancer Breast Neoplasms - diagnosis Breast Neoplasms - genetics Cancer diagnosis Cancer research Cancer treatment Cell Line, Tumor Diagnosis, Differential Early Detection of Cancer Endometrial cancer Endometrial Neoplasms - diagnosis Endometrial Neoplasms - genetics Endometrium Female Gene Expression Profiling - methods Gene Expression Regulation, Neoplastic Genes Genetic aspects Humans Investigations Kinases Medical diagnosis MicroRNA MicroRNAs - genetics miRNA Neoplasia Non-coding RNA Ovarian cancer Ovarian Neoplasms - diagnosis Ovarian Neoplasms - genetics Reverse transcription Scientific equipment industry Tumor suppressor genes |
title | Mutually distinguishing microRNA signatures of breast, ovarian and endometrial cancers in vitro |
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