MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma
We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into “early-stage” by the TNM staging system. A total of 836 early-s...
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Published in | Journal of oncology Vol. 2021; pp. 8292453 - 11 |
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Main Authors | , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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15.01.2021
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Abstract | We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into “early-stage” by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only (p<0.001); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2–0.6; p=0.0005). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls (p<0.0005). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients. |
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AbstractList | We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into “early-stage” by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only (
p
< 0.001); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2–0.6;
p
=0.0005). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls (
p
< 0.0005). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients. We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into "early-stage" by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only ( < 0.001); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2-0.6; =0.0005). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls ( < 0.0005). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients. We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into “early-stage” by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only (p<0.001); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2–0.6; p=0.0005). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls (p<0.0005). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients. We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into “early-stage” by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only ( p < 0.001 ); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2–0.6; p = 0.0005 ). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls ( p < 0.0005 ). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients. |
Author | Stewart, Claire R. Troob, Scott Shimonosono, Masataka Hernandez, Brenda Y. Levin, Matt AkhavanAghdam, Zohreh McDowell, Bradley D. Santella, Regina M. Shackelford, Austin J. Philipone, Elizabeth Yoon, Angela J. Carvajal, Richard D. Peters, Scott M. Nakagawa, Hiroshi Kutler, David I. Wang, Shuang Canterbury, Carleigh R. Momen-Heravi, Fatemeh Wang, Tian |
AuthorAffiliation | 5 Hawaii Tumor Registry, University of Hawaii Cancer Center, Honolulu, HI, USA 1 Columbia University Irving Medical Center, New York, NY, USA 2 Columbia University Mailman School of Public Health, New York, NY, USA 3 Weill Cornell Medicine, New York, NY, USA 6 Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA 4 Cell IDx, San Diego, CA, USA |
AuthorAffiliation_xml | – name: 2 Columbia University Mailman School of Public Health, New York, NY, USA – name: 1 Columbia University Irving Medical Center, New York, NY, USA – name: 6 Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA – name: 3 Weill Cornell Medicine, New York, NY, USA – name: 5 Hawaii Tumor Registry, University of Hawaii Cancer Center, Honolulu, HI, USA – name: 4 Cell IDx, San Diego, CA, USA |
Author_xml | – sequence: 1 givenname: Angela J. orcidid: 0000-0002-0529-7195 surname: Yoon fullname: Yoon, Angela J. organization: Columbia University Irving Medical CenterNew YorkNYUSAcolumbia.edu – sequence: 2 givenname: Regina M. surname: Santella fullname: Santella, Regina M. organization: Columbia University Mailman School of Public HealthNew YorkNYUSAcolumbia.edu – sequence: 3 givenname: Shuang surname: Wang fullname: Wang, Shuang organization: Columbia University Mailman School of Public HealthNew YorkNYUSAcolumbia.edu – sequence: 4 givenname: David I. surname: Kutler fullname: Kutler, David I. organization: Weill Cornell MedicineNew YorkNYUSAcornell.edu – sequence: 5 givenname: Richard D. surname: Carvajal fullname: Carvajal, Richard D. organization: Columbia University Irving Medical CenterNew YorkNYUSAcolumbia.edu – sequence: 6 givenname: Elizabeth surname: Philipone fullname: Philipone, Elizabeth organization: Columbia University Irving Medical CenterNew YorkNYUSAcolumbia.edu – sequence: 7 givenname: Tian surname: Wang fullname: Wang, Tian organization: Columbia University Mailman School of Public HealthNew YorkNYUSAcolumbia.edu – sequence: 8 givenname: Scott M. surname: Peters fullname: Peters, Scott M. organization: Columbia University Irving Medical CenterNew YorkNYUSAcolumbia.edu – sequence: 9 givenname: Claire R. surname: Stewart fullname: Stewart, Claire R. organization: Weill Cornell MedicineNew YorkNYUSAcornell.edu – sequence: 10 givenname: Fatemeh surname: Momen-Heravi fullname: Momen-Heravi, Fatemeh organization: Columbia University Irving Medical CenterNew YorkNYUSAcolumbia.edu – sequence: 11 givenname: Scott surname: Troob fullname: Troob, Scott organization: Columbia University Irving Medical CenterNew YorkNYUSAcolumbia.edu – sequence: 12 givenname: Matt surname: Levin fullname: Levin, Matt organization: Cell IDxSan DiegoCAUSA – sequence: 13 givenname: Zohreh surname: AkhavanAghdam fullname: AkhavanAghdam, Zohreh organization: Cell IDxSan DiegoCAUSA – sequence: 14 givenname: Austin J. surname: Shackelford fullname: Shackelford, Austin J. organization: Columbia University Irving Medical CenterNew YorkNYUSAcolumbia.edu – sequence: 15 givenname: Carleigh R. surname: Canterbury fullname: Canterbury, Carleigh R. organization: Columbia University Irving Medical CenterNew YorkNYUSAcolumbia.edu – sequence: 16 givenname: Masataka surname: Shimonosono fullname: Shimonosono, Masataka organization: Columbia University Irving Medical CenterNew YorkNYUSAcolumbia.edu – sequence: 17 givenname: Brenda Y. surname: Hernandez fullname: Hernandez, Brenda Y. organization: Hawaii Tumor RegistryUniversity of Hawaii Cancer CenterHonoluluHIUSAuhcancercenter.org – sequence: 18 givenname: Bradley D. surname: McDowell fullname: McDowell, Bradley D. organization: Holden Comprehensive Cancer CenterUniversity of IowaIowa CityIAUSAuiowa.edu – sequence: 19 givenname: Hiroshi surname: Nakagawa fullname: Nakagawa, Hiroshi organization: Columbia University Irving Medical CenterNew YorkNYUSAcolumbia.edu |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33510789$$D View this record in MEDLINE/PubMed |
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Cites_doi | 10.1126/science.aao2774 10.1038/nrc725 10.1038/s42003-019-0305-x 10.1016/j.jcmgh.2018.09.003 10.4103/jipo.jipo-5-19 10.1016/j.canlet.2004.06.047 10.1186/s12885-018-4247-3 10.1111/jop.12667 10.1002/hed.21017 10.2174/1568026616666160212122425 10.3892/ijo.2017.4093 10.1177/0022034518762090 10.1111/cts.12429 10.1016/j.oraloncology.2006.01.011 10.1186/s12943-016-0512-8 10.1590/1679-775720130317 10.3390/cells8080772 10.1158/1078-0432.ccr-12-2214 10.1016/j.oraloncology.2018.01.020 10.3322/caac.21389 10.1002/cpsc.109 10.1001/archoto.2010.214 10.1155/2002/452527 10.1001/archotol.128.1.58 10.1053/ejso.2001.1151 10.1038/nrd3979 10.1002/hed.26089 10.1158/2326-6066.cir-13-0001 10.1158/2159-8290.cd-18-1522 10.1002/hed.21356 10.1016/j.canep.2015.04.007 10.1158/2326-6066.cir-17-0360 10.3390/ijms19082413 10.1038/nm.4389 10.1517/17460441.2015.1058775 |
ContentType | Journal Article |
Copyright | Copyright © 2021 Angela J. Yoon et al. Copyright © 2021 Angela J. Yoon et al. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Copyright © 2021 Angela J. Yoon et al. 2021 |
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Snippet | We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in... |
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StartPage | 8292453 |
SubjectTerms | Clinical outcomes Dissection Genes Hispanic people Human papillomavirus Laboratories Lymphatic system Medical prognosis Metastasis MicroRNAs Mortality Oral cancer Patients Squamous cell carcinoma Surgery |
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Title | MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma |
URI | https://dx.doi.org/10.1155/2021/8292453 https://www.ncbi.nlm.nih.gov/pubmed/33510789 https://www.proquest.com/docview/2480125761/abstract/ https://search.proquest.com/docview/2483815895 https://pubmed.ncbi.nlm.nih.gov/PMC7822680 |
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