Salivary microRNAs identified by small RNA sequencing as potential predictors of response to intensity-modulated radiotherapy in head and neck cancer patients
Purpose Progress in radiation therapy of head and neck squamous cell carcinomas (HNSCCs) is logically linked to the development of molecular predictors that would help to enhance individually tailored treatment. MicroRNA (miRNA) expression profiles in tumors have repeatedly been tested to optimize t...
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| Veröffentlicht in: | Cellular oncology (Dordrecht) 2020-06, Vol.43 (3), p.505-511 |
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| creator | Ahmad, Parwez Slavik, Marek Trachtova, Karolina Gablo, Natalia Anna Kazda, Tomas Gurin, Dominik Smilek, Pavel Horakova, Zuzana Gal, Bretislav Hermanova, Marketa Slampa, Pavel Sana, Jiri Slaby, Ondrej |
| description | Purpose
Progress in radiation therapy of head and neck squamous cell carcinomas (HNSCCs) is logically linked to the development of molecular predictors that would help to enhance individually tailored treatment. MicroRNA (miRNA) expression profiles in tumors have repeatedly been tested to optimize the molecular diagnostics of HNSCC. In addition to tumor tissues, miRNAs are stably present in body fluids, including saliva, and can thus be collected non-invasively. The aim of our current study was to evaluate whether salivary miRNAs have potential as response predictors in HNSCC patients treated with intensity modulated radiation therapy (IMRT).
Methods
In total 48 HNSCC patients treated by definitive IMRT were enrolled in our prospective study. To identify predictive salivary miRNAs, we used small RNA sequencing in 14 saliva samples of HNSCC patients and qRT-PCR validation of selected miRNA candidates in an independent set of 34 patients.
Results
We found that salivary miR-15a-5p and miR-15b-5p exhibited differential levels between patients with and without complete remission (
p
= 0.025 and
p
= 0.028, respectively). Subsequent Kaplan-Meier analysis confirmed that patients with higher levels of miR-15a-5p reached a significantly longer locoregional progression-free survival (LPFS) than those with low levels (
p
= 0.024). Finally, multivariate Cox regression analysis revealed that miR-15a-5p may serve as an independent predictive biomarker of LPFS in HNSCC patients treated with IMRT (HR 0.104; 95% CI 0.004–0.911;
p
= 0.04).
Conclusions
We conclude that salivary miR-15a-5p may represent a potential biomarker for individualized treatment decision-making in HNSCC patients. |
| doi_str_mv | 10.1007/s13402-020-00507-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2387656378</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2387656378</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-fa91902f494239b47308eb461e6b47bc0182c9bc54e42f8b3d1bbf43360f40df3</originalsourceid><addsrcrecordid>eNp9kcluFTEQRVsIRKKQH2CBLLFh08FTT8soYogUgcSwttx2OXHothuXH9L7Gb6VCi8EiQXe2Fadunbd2zTPBT8TnA-vUSjNZcslbznv-NAOj5pjKYVolVb944ezHI-aU8RbTkv3ou_6p82RkrLvu246bn5-tkv8YcuerdGV_OnDObLoIdUYIng27xmudlkYFRjC9x0kF9M1s8i2XO8wu7CtgI-u5oIsB1YAt5wQWM0sJmIw1n27Zr9bbCXJYn3M9QaK3fYEsBuwntnkWQL3jTmbHBS22RpJHZ81T4JdEE7v95Pm69s3Xy7et1cf311enF-1Tg1dbYOdxMRl0JOWapr1oPgIM40LPV1mx8Uo3TS7ToOWYZyVF_MctFI9D5r7oE6aVwfdrWQaEqtZIzpYFpsg79BINQ5knRpGQl_-g97mXUn0OyM1F1KPspuIkgeKTEUsEMxW4ko-G8HNXYDmEKChAM3vAM1ATS_upXfzCv6h5U9cBKgDgFRK11D-vv0f2V-CP6gI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2401248259</pqid></control><display><type>article</type><title>Salivary microRNAs identified by small RNA sequencing as potential predictors of response to intensity-modulated radiotherapy in head and neck cancer patients</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Ahmad, Parwez ; Slavik, Marek ; Trachtova, Karolina ; Gablo, Natalia Anna ; Kazda, Tomas ; Gurin, Dominik ; Smilek, Pavel ; Horakova, Zuzana ; Gal, Bretislav ; Hermanova, Marketa ; Slampa, Pavel ; Sana, Jiri ; Slaby, Ondrej</creator><creatorcontrib>Ahmad, Parwez ; Slavik, Marek ; Trachtova, Karolina ; Gablo, Natalia Anna ; Kazda, Tomas ; Gurin, Dominik ; Smilek, Pavel ; Horakova, Zuzana ; Gal, Bretislav ; Hermanova, Marketa ; Slampa, Pavel ; Sana, Jiri ; Slaby, Ondrej</creatorcontrib><description>Purpose
Progress in radiation therapy of head and neck squamous cell carcinomas (HNSCCs) is logically linked to the development of molecular predictors that would help to enhance individually tailored treatment. MicroRNA (miRNA) expression profiles in tumors have repeatedly been tested to optimize the molecular diagnostics of HNSCC. In addition to tumor tissues, miRNAs are stably present in body fluids, including saliva, and can thus be collected non-invasively. The aim of our current study was to evaluate whether salivary miRNAs have potential as response predictors in HNSCC patients treated with intensity modulated radiation therapy (IMRT).
Methods
In total 48 HNSCC patients treated by definitive IMRT were enrolled in our prospective study. To identify predictive salivary miRNAs, we used small RNA sequencing in 14 saliva samples of HNSCC patients and qRT-PCR validation of selected miRNA candidates in an independent set of 34 patients.
Results
We found that salivary miR-15a-5p and miR-15b-5p exhibited differential levels between patients with and without complete remission (
p
= 0.025 and
p
= 0.028, respectively). Subsequent Kaplan-Meier analysis confirmed that patients with higher levels of miR-15a-5p reached a significantly longer locoregional progression-free survival (LPFS) than those with low levels (
p
= 0.024). Finally, multivariate Cox regression analysis revealed that miR-15a-5p may serve as an independent predictive biomarker of LPFS in HNSCC patients treated with IMRT (HR 0.104; 95% CI 0.004–0.911;
p
= 0.04).
Conclusions
We conclude that salivary miR-15a-5p may represent a potential biomarker for individualized treatment decision-making in HNSCC patients.</description><identifier>ISSN: 2211-3428</identifier><identifier>EISSN: 2211-3436</identifier><identifier>DOI: 10.1007/s13402-020-00507-7</identifier><identifier>PMID: 32266559</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Aged ; Biomarkers ; Biomedical and Life Sciences ; Biomedicine ; Body fluids ; Cancer Research ; Decision making ; Female ; Head & neck cancer ; Head and neck carcinoma ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - radiotherapy ; Humans ; Male ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Middle Aged ; miRNA ; Oncology ; Pathology ; Progression-Free Survival ; Proportional Hazards Models ; Radiation therapy ; Radiotherapy, Intensity-Modulated ; Remission ; Saliva ; Saliva - metabolism ; Sequence Analysis, RNA ; Short Communication ; Squamous cell carcinoma ; Tumors</subject><ispartof>Cellular oncology (Dordrecht), 2020-06, Vol.43 (3), p.505-511</ispartof><rights>International Society for Cellular Oncology 2020</rights><rights>International Society for Cellular Oncology 2020.</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-fa91902f494239b47308eb461e6b47bc0182c9bc54e42f8b3d1bbf43360f40df3</citedby><cites>FETCH-LOGICAL-c375t-fa91902f494239b47308eb461e6b47bc0182c9bc54e42f8b3d1bbf43360f40df3</cites><orcidid>0000-0002-8450-0584</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13402-020-00507-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13402-020-00507-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32266559$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ahmad, Parwez</creatorcontrib><creatorcontrib>Slavik, Marek</creatorcontrib><creatorcontrib>Trachtova, Karolina</creatorcontrib><creatorcontrib>Gablo, Natalia Anna</creatorcontrib><creatorcontrib>Kazda, Tomas</creatorcontrib><creatorcontrib>Gurin, Dominik</creatorcontrib><creatorcontrib>Smilek, Pavel</creatorcontrib><creatorcontrib>Horakova, Zuzana</creatorcontrib><creatorcontrib>Gal, Bretislav</creatorcontrib><creatorcontrib>Hermanova, Marketa</creatorcontrib><creatorcontrib>Slampa, Pavel</creatorcontrib><creatorcontrib>Sana, Jiri</creatorcontrib><creatorcontrib>Slaby, Ondrej</creatorcontrib><title>Salivary microRNAs identified by small RNA sequencing as potential predictors of response to intensity-modulated radiotherapy in head and neck cancer patients</title><title>Cellular oncology (Dordrecht)</title><addtitle>Cell Oncol</addtitle><addtitle>Cell Oncol (Dordr)</addtitle><description>Purpose
Progress in radiation therapy of head and neck squamous cell carcinomas (HNSCCs) is logically linked to the development of molecular predictors that would help to enhance individually tailored treatment. MicroRNA (miRNA) expression profiles in tumors have repeatedly been tested to optimize the molecular diagnostics of HNSCC. In addition to tumor tissues, miRNAs are stably present in body fluids, including saliva, and can thus be collected non-invasively. The aim of our current study was to evaluate whether salivary miRNAs have potential as response predictors in HNSCC patients treated with intensity modulated radiation therapy (IMRT).
Methods
In total 48 HNSCC patients treated by definitive IMRT were enrolled in our prospective study. To identify predictive salivary miRNAs, we used small RNA sequencing in 14 saliva samples of HNSCC patients and qRT-PCR validation of selected miRNA candidates in an independent set of 34 patients.
Results
We found that salivary miR-15a-5p and miR-15b-5p exhibited differential levels between patients with and without complete remission (
p
= 0.025 and
p
= 0.028, respectively). Subsequent Kaplan-Meier analysis confirmed that patients with higher levels of miR-15a-5p reached a significantly longer locoregional progression-free survival (LPFS) than those with low levels (
p
= 0.024). Finally, multivariate Cox regression analysis revealed that miR-15a-5p may serve as an independent predictive biomarker of LPFS in HNSCC patients treated with IMRT (HR 0.104; 95% CI 0.004–0.911;
p
= 0.04).
Conclusions
We conclude that salivary miR-15a-5p may represent a potential biomarker for individualized treatment decision-making in HNSCC patients.</description><subject>Aged</subject><subject>Biomarkers</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Body fluids</subject><subject>Cancer Research</subject><subject>Decision making</subject><subject>Female</subject><subject>Head & neck cancer</subject><subject>Head and neck carcinoma</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - radiotherapy</subject><subject>Humans</subject><subject>Male</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Oncology</subject><subject>Pathology</subject><subject>Progression-Free Survival</subject><subject>Proportional Hazards Models</subject><subject>Radiation therapy</subject><subject>Radiotherapy, Intensity-Modulated</subject><subject>Remission</subject><subject>Saliva</subject><subject>Saliva - metabolism</subject><subject>Sequence Analysis, RNA</subject><subject>Short Communication</subject><subject>Squamous cell carcinoma</subject><subject>Tumors</subject><issn>2211-3428</issn><issn>2211-3436</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcluFTEQRVsIRKKQH2CBLLFh08FTT8soYogUgcSwttx2OXHothuXH9L7Gb6VCi8EiQXe2Fadunbd2zTPBT8TnA-vUSjNZcslbznv-NAOj5pjKYVolVb944ezHI-aU8RbTkv3ou_6p82RkrLvu246bn5-tkv8YcuerdGV_OnDObLoIdUYIng27xmudlkYFRjC9x0kF9M1s8i2XO8wu7CtgI-u5oIsB1YAt5wQWM0sJmIw1n27Zr9bbCXJYn3M9QaK3fYEsBuwntnkWQL3jTmbHBS22RpJHZ81T4JdEE7v95Pm69s3Xy7et1cf311enF-1Tg1dbYOdxMRl0JOWapr1oPgIM40LPV1mx8Uo3TS7ToOWYZyVF_MctFI9D5r7oE6aVwfdrWQaEqtZIzpYFpsg79BINQ5knRpGQl_-g97mXUn0OyM1F1KPspuIkgeKTEUsEMxW4ko-G8HNXYDmEKChAM3vAM1ATS_upXfzCv6h5U9cBKgDgFRK11D-vv0f2V-CP6gI</recordid><startdate>20200601</startdate><enddate>20200601</enddate><creator>Ahmad, Parwez</creator><creator>Slavik, Marek</creator><creator>Trachtova, Karolina</creator><creator>Gablo, Natalia Anna</creator><creator>Kazda, Tomas</creator><creator>Gurin, Dominik</creator><creator>Smilek, Pavel</creator><creator>Horakova, Zuzana</creator><creator>Gal, Bretislav</creator><creator>Hermanova, Marketa</creator><creator>Slampa, Pavel</creator><creator>Sana, Jiri</creator><creator>Slaby, Ondrej</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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><orcidid>https://orcid.org/0000-0002-8450-0584</orcidid></search><sort><creationdate>20200601</creationdate><title>Salivary microRNAs identified by small RNA sequencing as potential predictors of response to intensity-modulated radiotherapy in head and neck cancer patients</title><author>Ahmad, Parwez ; Slavik, Marek ; Trachtova, Karolina ; Gablo, Natalia Anna ; Kazda, Tomas ; Gurin, Dominik ; Smilek, Pavel ; Horakova, Zuzana ; Gal, Bretislav ; Hermanova, Marketa ; Slampa, Pavel ; Sana, Jiri ; Slaby, Ondrej</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-fa91902f494239b47308eb461e6b47bc0182c9bc54e42f8b3d1bbf43360f40df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Biomarkers</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Body fluids</topic><topic>Cancer Research</topic><topic>Decision making</topic><topic>Female</topic><topic>Head & neck cancer</topic><topic>Head and neck carcinoma</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Head and Neck Neoplasms - radiotherapy</topic><topic>Humans</topic><topic>Male</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Oncology</topic><topic>Pathology</topic><topic>Progression-Free Survival</topic><topic>Proportional Hazards Models</topic><topic>Radiation therapy</topic><topic>Radiotherapy, Intensity-Modulated</topic><topic>Remission</topic><topic>Saliva</topic><topic>Saliva - metabolism</topic><topic>Sequence Analysis, RNA</topic><topic>Short Communication</topic><topic>Squamous cell carcinoma</topic><topic>Tumors</topic><toplevel>online_resources</toplevel><creatorcontrib>Ahmad, Parwez</creatorcontrib><creatorcontrib>Slavik, Marek</creatorcontrib><creatorcontrib>Trachtova, Karolina</creatorcontrib><creatorcontrib>Gablo, Natalia Anna</creatorcontrib><creatorcontrib>Kazda, Tomas</creatorcontrib><creatorcontrib>Gurin, Dominik</creatorcontrib><creatorcontrib>Smilek, Pavel</creatorcontrib><creatorcontrib>Horakova, Zuzana</creatorcontrib><creatorcontrib>Gal, Bretislav</creatorcontrib><creatorcontrib>Hermanova, Marketa</creatorcontrib><creatorcontrib>Slampa, Pavel</creatorcontrib><creatorcontrib>Sana, Jiri</creatorcontrib><creatorcontrib>Slaby, Ondrej</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>Cellular oncology (Dordrecht)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ahmad, Parwez</au><au>Slavik, Marek</au><au>Trachtova, Karolina</au><au>Gablo, Natalia Anna</au><au>Kazda, Tomas</au><au>Gurin, Dominik</au><au>Smilek, Pavel</au><au>Horakova, Zuzana</au><au>Gal, Bretislav</au><au>Hermanova, Marketa</au><au>Slampa, Pavel</au><au>Sana, Jiri</au><au>Slaby, Ondrej</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Salivary microRNAs identified by small RNA sequencing as potential predictors of response to intensity-modulated radiotherapy in head and neck cancer patients</atitle><jtitle>Cellular oncology (Dordrecht)</jtitle><stitle>Cell Oncol</stitle><addtitle>Cell Oncol (Dordr)</addtitle><date>2020-06-01</date><risdate>2020</risdate><volume>43</volume><issue>3</issue><spage>505</spage><epage>511</epage><pages>505-511</pages><issn>2211-3428</issn><eissn>2211-3436</eissn><abstract>Purpose
Progress in radiation therapy of head and neck squamous cell carcinomas (HNSCCs) is logically linked to the development of molecular predictors that would help to enhance individually tailored treatment. MicroRNA (miRNA) expression profiles in tumors have repeatedly been tested to optimize the molecular diagnostics of HNSCC. In addition to tumor tissues, miRNAs are stably present in body fluids, including saliva, and can thus be collected non-invasively. The aim of our current study was to evaluate whether salivary miRNAs have potential as response predictors in HNSCC patients treated with intensity modulated radiation therapy (IMRT).
Methods
In total 48 HNSCC patients treated by definitive IMRT were enrolled in our prospective study. To identify predictive salivary miRNAs, we used small RNA sequencing in 14 saliva samples of HNSCC patients and qRT-PCR validation of selected miRNA candidates in an independent set of 34 patients.
Results
We found that salivary miR-15a-5p and miR-15b-5p exhibited differential levels between patients with and without complete remission (
p
= 0.025 and
p
= 0.028, respectively). Subsequent Kaplan-Meier analysis confirmed that patients with higher levels of miR-15a-5p reached a significantly longer locoregional progression-free survival (LPFS) than those with low levels (
p
= 0.024). Finally, multivariate Cox regression analysis revealed that miR-15a-5p may serve as an independent predictive biomarker of LPFS in HNSCC patients treated with IMRT (HR 0.104; 95% CI 0.004–0.911;
p
= 0.04).
Conclusions
We conclude that salivary miR-15a-5p may represent a potential biomarker for individualized treatment decision-making in HNSCC patients.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>32266559</pmid><doi>10.1007/s13402-020-00507-7</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-8450-0584</orcidid></addata></record> |
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| ispartof | Cellular oncology (Dordrecht), 2020-06, Vol.43 (3), p.505-511 |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Aged Biomarkers Biomedical and Life Sciences Biomedicine Body fluids Cancer Research Decision making Female Head & neck cancer Head and neck carcinoma Head and Neck Neoplasms - genetics Head and Neck Neoplasms - radiotherapy Humans Male MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism Middle Aged miRNA Oncology Pathology Progression-Free Survival Proportional Hazards Models Radiation therapy Radiotherapy, Intensity-Modulated Remission Saliva Saliva - metabolism Sequence Analysis, RNA Short Communication Squamous cell carcinoma Tumors |
| title | Salivary microRNAs identified by small RNA sequencing as potential predictors of response to intensity-modulated radiotherapy in head and neck cancer patients |
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