Grant Details
Grant Number: |
1R03CA186261-01A1 Interpret this number |
Primary Investigator: |
Li, Guojun |
Organization: |
University Of Tx Md Anderson Can Ctr |
Project Title: |
Inflammatory Response Mirnas Predict HPV-Associated Oropharyngeal Cancer Outcome |
Fiscal Year: |
2015 |
Abstract
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DESCRIPTION (provided by applicant): Squamous cell carcinoma of the oropharynx (SCCOP) is characterized by local tumor aggressiveness requiring morbid local-regional therapies with poor survival and high recurrence rates. Despite declining smoking prevalence, the incidence of SCCOP is increasing, particularly in young adults. These trends may be due to the rising prevalence of oncogenic human papillomavirus (HPV) in the population. HPV-positive [(HPV+)] SCCOP is a distinct epidemiologic, clinical, and molecular disease with potentially unique clinical behavior and treatment responses. Identification of those needing treatment intensification and those able to benefit from reduction of treatment intensity is critical to more
effective and less morbid treatment. Oncogenic subtypes of HPV are critical etiologic factors in a distinct subset of head and neck cancers, chiefly SCCOP. Inflammatory response miRNAs which control the HPV clearance and escape of immune surveillance may contribute to HPV(+) tumors and related outcomes of SCCOP. In addition, miRNAs in human serum hold a great potential for serum-based biomarker research. Thus, serum expression profiles of inflammatory response miRNAs before treatment may affect tumor HPV status and related outcomes of SCCOP patients; and exploitation of such associations may help develop clinically relevant non-tumor-based biomarkers for HPV- associated SCCOP patients. In this study, the study subjects will be 600 patients with incident SCCOP identified from an existing molecular epidemiologic study of squamous cell carcinoma of the head and neck. The specific aims for this R03 project are: Aim 1: To assess if serum expression profiles of selected inflammatory/immune response miRNAs before treatment are markers of tumor HPV status among the 600 SCCOP patients. We will determine serum expression of those selected miRNAs before treatment by using the miScript miRNA PCR arrays method and Aim 2: To determine if certain serum expression profiles of above miRNAs before treatment as blood-based and non-tumor predictors of clinical outcomes of HPV(+) SCCOP patients including disease-specific survival, disease-free survival, and overall survival among 600 SCCOP patients treated and followed at U.T. MDACC. By knowing the tumor HPV status and identifying novel prognostic biomarkers of HPV-associated SCCOP patients, physicians can effectively tailor treatment, screening, and follow-up strategies for an improved survival and a better quality of life as well as greatly enhanced secondary cancer prevention.
Publications
A genetic variant within MDM4 3'UTR miRNA binding site is associated with HPV16-positive tumors and survival of oropharyngeal cancer.
Authors: Zhang Y.
, Sturgis E.M.
, Wei P.
, Liu H.
, Wang Z.
, Ma Y.
, Liu C.
, Gu K.J.
, Wei Q.
, Li G.
.
Source: Molecular Carcinogenesis, 2019-09-12 00:00:00.0; , .
EPub date: 2019-09-12 00:00:00.0.
PMID: 31513313
Related Citations
Lymphocyte telomere length predicts clinical outcomes of HPV-positive oropharyngeal cancer patients after definitive radiotherapy.
Authors: Luo X.
, Sturgis E.M.
, Yang Z.
, Sun Y.
, Wei P.
, Liu Z.
, Wei Q.
, Li G.
.
Source: Carcinogenesis, 2019-07-06 00:00:00.0; 40(6), p. 735-741.
PMID: 30721961
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The Modifying Effect of a Functional Variant at the miRNA Binding Site in E2F1 Gene on Recurrence of Oropharyngeal Cancer Patients with Definitive Radiotherapy.
Authors: Zhang H.
, Sturgis E.
, Zhu L.
, Lu Z.
, Tao Y.
, Zheng H.
, Li G.
.
Source: Translational Oncology, 2018 Jun; 11(3), p. 633-638.
EPub date: 2018-03-22 00:00:00.0.
PMID: 29574328
Related Citations
A TGF-β1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16-associated oropharyngeal cancer.
Authors: Tao Y.
, Sturgis E.M.
, Huang Z.
, Sun Y.
, Dahlstrom K.R.
, Wei Q.
, Li G.
.
Source: International Journal Of Cancer, 2018-04-16 00:00:00.0; , .
EPub date: 2018-04-16 00:00:00.0.
PMID: 29663347
Related Citations
TGF-β1 genetic variants predict clinical outcomes of HPV-positive oropharyngeal cancer patients after definitive radiotherapy.
Authors: Li G.
, Sturgis E.
, Tao Y.
, Huang Z.
, Wei Q.
, Wang Y.
, Wei P.
, Wang R.
.
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2018-02-20 00:00:00.0; , .
EPub date: 2018-02-20 00:00:00.0.
PMID: 29463556
Related Citations
Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx.
Authors: Lu Z.
, Sturgis E.M.
, Zhu L.
, Zhang H.
, Tao Y.
, Wei P.
, Wei Q.
, Li G.
.
Source: Molecular Carcinogenesis, 2017-10-26 00:00:00.0; , .
EPub date: 2017-10-26 00:00:00.0.
PMID: 29073727
Related Citations
MDM4 genetic variants predict HPV16-positive tumors of patients with squamous cell carcinoma of the oropharynx.
Authors: Lu Z.
, Zhang H.
, Tao Y.
, Li X.
, Li G.
.
Source: Oncotarget, 2017-10-17 00:00:00.0; 8(49), p. 86710-86717.
EPub date: 2017-09-30 00:00:00.0.
PMID: 29156829
Related Citations
Genetic variants in microRNA-binding sites of DNA repair genes as predictors of recurrence in patients with squamous cell carcinoma of the oropharynx.
Authors: Zhu L.
, Sturgis E.M.
, Zhang H.
, Lu Z.
, Tao Y.
, Wei Q.
, Li G.
.
Source: International Journal Of Cancer, 2017-10-01 00:00:00.0; 141(7), p. 1355-1364.
EPub date: 2017-07-07 00:00:00.0.
PMID: 28646528
Related Citations
E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx.
Authors: Li Y.
, Sturgis E.M.
, Zhu L.
, Cao X.
, Wei Q.
, Zhang H.
, Li G.
.
Source: Molecular Carcinogenesis, 2017 04; 56(4), p. 1335-1343.
EPub date: 2017-01-02 00:00:00.0.
PMID: 27864908
Related Citations
Association between miRNA-binding site polymorphisms in double-strand break repair genes and risk of recurrence in patients with squamous cell carcinomas of the non-oropharynx.
Authors: Zhu L.
, Sturgis E.M.
, Lu Z.
, Zhang H.
, Wei P.
, Wei Q.
, Li G.
.
Source: Carcinogenesis, 2017-04-01 00:00:00.0; 38(4), p. 432-438.
PMID: 28334093
Related Citations
Modifying Effect Of Mouse Double Minute-2 Promoter Variants On Risk Of Recurrence For Patients With Squamous Cell Carcinoma Of Oropharynx
Authors: Zhang Y.
, Sturgis E.M.
, Li Y.
, Wei Q.
, Huang Z.
, Li G.
.
Source: Scientific Reports, 2017-01-03 00:00:00.0; 7, p. 39765.
PMID: 28045062
Related Citations
Effect of human papillomavirus seropositivity and E2F2 promoter variants on risk of squamous cell carcinomas of oropharynx and oral cavity.
Authors: Li Y.
, Sturgis E.M.
, Yuan Y.
, Lu M.
, Cao X.
, Wei Q.
, Li G.
.
Source: Carcinogenesis, 2016-11-01 00:00:00.0; 37(11), p. 1070-1078.
PMID: 27609456
Related Citations
Significance Of Microrna-related Variants In Susceptibility To Recurrence Of Oropharyngeal Cancer Patients After Definitive Radiotherapy
Authors: Chen X.
, Sturgis E.M.
, Wang C.
, Cao X.
, Li Y.
, Wei Q.
, Li G.
.
Source: Oncotarget, 2016-06-07 00:00:00.0; 7(23), p. 35015-25.
PMID: 27145460
Related Citations
Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy.
Authors: Zhang F.
, Sturgis E.M.
, Sun Y.
, Zhang Y.
, Wei Q.
, Zhang C.
, Zheng H.
, Li G.
.
Source: International Journal Of Cancer, 2015-11-15 00:00:00.0; 137(10), p. 2454-61.
EPub date: 2015-11-15 00:00:00.0.
PMID: 25976983
Related Citations
A functional variant at miRNA-122 binding site in IL-1¿ 3' UTR predicts risk and HPV-positive tumours of oropharyngeal cancer.
Authors: Zhang Y.
, Sturgis E.M.
, Sun Y.
, Sun C.
, Wei Q.
, Huang Z.
, Li G.
.
Source: European Journal Of Cancer (oxford, England : 1990), 2015 Jul; 51(11), p. 1415-23.
PMID: 25981582
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