Methods for detecting expression of lnc-FANCI-2 in cervical cells
Inventors
ZHENG, ZHI-MING • XU, JUNFEN • Zhu, Jun • YANG, YANQIN • Wang, Xiaohong
Assignees
US Department of Health and Human Services
Publication Number
US-10487365-B2
Publication Date
2019-11-26
Expiration Date
2036-09-20
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Abstract
Described herein are biomarkers for HPV-associated pre-cancers and cancers such as cervical cancer and cervical intraepithelial neoplasia. The RNA binding protein (RBP) and long-noncoding RNA (lnc-RNA) biomarkers can be detected and used to diagnose HPV-associated pre-cancers and cancers. In addition, early diagnosis of HPV-associated pre-cancers and cancers can facilitate therapeutic intervention in patients, particularly in the pre-cancer stage which can delay or prevent progression to cancer.
Core Innovation
The invention describes novel polynucleotide biomarkers that can be detected and used for diagnosis of HPV-associated pre-cancers and cancers such as cervical cancer and cervical intraepithelial neoplasia. Specifically, RNA binding proteins (RBPs) and long noncoding RNAs (lnc-RNAs) serve as biomarkers whose expression levels correlate with cervical cancer progression. Early diagnosis using these biomarkers can facilitate therapeutic intervention particularly at pre-cancer stages, potentially delaying or preventing progression to cancer.
The problem addressed is the need for diagnostic markers that enable early diagnosis of high-risk HPV infection, HPV-associated pre-cancer, and HPV-associated cancer to develop effective intervention strategies. High-risk HPV persistent infection contributes significantly to cervical cancer, which is a leading cause of death in women worldwide, with a large number of cases occurring in developing countries.
In the inventive method, detection and quantitation of specific polynucleotide biomarkers such as lnc-FANCI-2, lnc-GLB1L2-1, and several RBPs including GRB7, NOVA1, RNASEH2A, and CDKN2A in cervical cell samples are used to determine cervical intraepithelial neoplasia stages or cervical cancer. This is done by correlating the expression levels of biomarkers in test samples to reference samples with known disease states, enabling classification, diagnosis, and informed treatment decisions.
Claims Coverage
The patent includes one independent claim focusing on quantitating expression levels of lnc-FANCI-2 in cervical cell samples using specific polynucleotide probes and comparing to normal control levels for diagnosis.
Quantitation of lnc-FANCI-2 expression in cervical cell samples
A method of quantifying expression level of lnc-FANCI-2 polynucleotide in a sample from cervix of a test patient by contacting the sample with one or more polynucleotides that hybridize to lnc-FANCI-2 (specifically SEQ ID NOs: 78, 79, 80), detecting hybridization level, comparing it to a control hybridization level in normal cervical tissue samples, and determining differential expression when the test level is at least 300% of control level.
Use of real-time RT-PCR for detection
The method further provides that detection of hybridization between polynucleotides and lnc-FANCI-2 is conducted using real-time reverse transcriptase PCR techniques.
Types of cervical samples for testing
The sample comprising cervical cells can be any of a PAP smear, a vaginal wash, or a cervical biopsy specimen from the test patient.
The claims focus on a diagnostic method for cervical cancer or precancer stages based on detecting and quantifying lnc-FANCI-2 polynucleotide expression levels in cervical cell samples using specific hybridization probes and comparing to control normal levels, optionally employing real-time RT-PCR and using various cervical sample types.
Stated Advantages
Early diagnosis of HPV-associated pre-cancers and cancers allows therapeutic intervention particularly in pre-cancer stages to delay or prevent progression to cancer.
The biomarkers identified provide a comprehensive expression atlas to improve diagnosis and treatment of cervical cancer.
Methods can classify disease state with statistical models enhancing prediction and enable minor surgical interventions at early disease stages which are effective and less invasive.
Documented Applications
Diagnosis and classification of HPV-associated pre-cancers and cancers such as cervical cancer and cervical intraepithelial neoplasia by detecting expression levels of specific RBP and lnc-RNA biomarkers in cervical cell samples.
Early screening and monitoring of patients at risk for cervical cancer or HPV infection by using biomarkers from PAP smears, vaginal washes, or cervical biopsies.
Therapeutic intervention planning for patients identified with stage 1, 2, or 3 cervical intraepithelial neoplasia or cervical cancer based on biomarker expression profiling.
Use of polynucleotide probe sets on solid supports for detection and quantitation of expression levels of biomarker polynucleotides in diagnostic assays.
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