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EP-4735642-A1 - METHODS, COMPOSITIONS, AND SYSTEMS TO DETECT HEAD AND NECK CANCER IN SALIVA SAMPLES

EP4735642A1EP 4735642 A1EP4735642 A1EP 4735642A1EP-4735642-A1

Abstract

Disclosed are methods, compositions, and systems to detect head and neck cancer using saliva samples. For example, the method may measure the presence and/or amount of a biomarker associated with Head and Neck Squamous Cell Carcinoma (HNSCC) in an individual by obtaining a saliva sample from the individual and measuring in the saliva sample an amount of an expression product from at least one gene encoding the biomarkers associated with HNSCC, wherein the genes comprise at least one of AIM2, CDSN, INHBA, MMP1, MMP9, or MMP10.

Inventors

  • WALLWEBER, GERALD J.

Assignees

  • Laboratory Corporation of America Holdings

Dates

Publication Date
20260506
Application Date
20240628

Claims (20)

  1. 1. A method to measure the presence and/or amount of a biomarker associated with Head and Neck Squamous Cell Carcinoma (HNSCC) in an individual comprising the steps of: (a) obtaining a saliva sample from the individual; and (b) measuring in the saliva sample an amount of an expression product from at least one gene encoding the biomarkers associated with HNSCC, wherein the genes comprise at least one of AIM2, CDSN, INHBA, MMP1, MMP9 or MMP10.
  2. 2. The method of claim 1, further comprising measuring the expression product from at least one of MMP13, CRISP3, MUC21, ADAM 12, MMP3 or ISG15.
  3. 3. The method of claim 1, further comprising measuring the expression product from any of the genes shown in Tables 1, 2, 5 or 6.
  4. 4. The method of claim 1, further comprising measuring the expression product of a housekeeping gene and normalizing the results.
  5. 5. A method of identifying an individual at risk for Head and Neck Squamous Cell Carcinoma (HNSCC), comprising the steps of: (a) obtaining a saliva sample from the individual; and (b) measuring in the saliva sample an amount of an expression product from at least one gene encoding the biomarkers associated with HNSCC, wherein the genes comprise at least one of AIM2, CDSN, INHBA, MMP1, MMP9, or MMP10, wherein the presence of an altered level of the expression product as compared to a healthy control for the biomarker associated with HNSCC identifies the individual as being at risk for HNSCC.
  6. 6. The method of claim 5, further comprising measuring the expression product from at least one of MMP13, CRISP3, MUC21, ADAM 12, MMP3 or ISG15.
  7. 7. The method of claim 5, further comprising measuring the expression product from any of the genes shown in Tables 1, 2, 5 or 6.
  8. 8. The method of claim 5, further comprising measuring expression of a housekeeping gene and normalizing the results.
  9. 9. A method of identifying an individual with Head and Neck Squamous Cell Carcinoma (HNSCC) and treating the individual, comprising the steps of: (a) obtaining a saliva sample from the individual; (b) measuring in the saliva sample an altered amount of an expression product from at least one gene encoding the biomarkers associated with HNSCC, wherein the genes comprise at least one of AIM2, CDSN, INHBA, MMP1, MMP9, or MMP10; and (c) administering to the individual one or more HNSCC treatments.
  10. 10. The method of claim 9, further comprising measuring the expression product from at least one of MMP13, CRISP3, MUC21, ADAM 12, MMP3 or ISG15.
  11. 11. The method of claim 9, further comprising measuring the expression product from at least one of any of the genes shown in Tables 1, 2, 5 or 6.
  12. 12. The method of claim 9, further comprising measuring expression of a housekeeping gene and normalizing the results.
  13. 13. A method of identifying an individual at risk for Head and Neck Squamous Cell Carcinoma (HNSCC) and monitoring the individual, comprising the steps of: (a) obtaining a saliva sample from the individual; (b) measuring in the saliva sample an increased amount of an expression product from at least one gene encoding the biomarkers associated with HNSCC, wherein the genes comprise at least one of AIM2, CDSN, INHBA, MMP1, MMP9, or MMP10; (c) determining that at least one of AIM2, CDSN, INHBA, MMP1, MMP9, or MMP10 have altered expression as compared to a healthy control; and (d) repeating steps (a)-(c) at a later time-point to determine if the at least one of AIM2, CDSN, INHBA, MMP1, MMP9, or MMP10 shows an increase in altered expression as compared to a healthy control.
  14. 14. The method of claim 13, further comprising measuring the expression product from at least one of MMP13, CRISP3, MUC21, ADAM 12, MMP3 or ISG15 in step (b) and determining that at least one of MMP13, CRISP3, MUC21, ADAM12, MMP3 or ISG15 have altered expression in step (c) and repeating steps (a)-(c) at a later time-point to determine if the at least one of MMP13, CRISP3, MUC21, ADAM 12, MMP3 or ISG15 shows an increase in altered expression as compared to a healthy control in step (d).
  15. 15. The method of claim 13, further comprising measuring the expression product from at least one of any of the genes shown in Tables 1, 2, 5 or 6 in step (b), determining that at least one of any of the genes shown in Tables 1, 2, 5 or 6 have altered expression in step (c) and repeating steps (a)-(c) at a later time-point to determine if the at least one of any of the genes shown in Tables 1, 2, 5 or 6 shows an increase in altered expression as compared to a healthy control in step (d).
  16. 16. The method of claim 13, further comprising measuring expression of a housekeeping gene and normalizing the results.
  17. 17. The method of any one of claims 1-16, wherein the expression product is a protein or an mRNA.
  18. 18. The method of claim 1-17, wherein the step of measuring comprises duplex ddPCR or multiplex ddPCR.
  19. 19. The method of any one of claims 1-17, wherein the step of detecting comprises an array of expression products.
  20. 20. A kit comprising a reagent to detect at least one of AIM2, CDSN, INHBA, MMP1, MMP9, or MMP10 in saliva and instructions for use.

Description

METHODS, COMPOSITIONS, AND SYSTEMS TO DETECT HEAD AND NECK CANCER IN SALIVA SAMPLES FIELD [0001] Disclosed are methods, compositions, and systems to detect head and neck cancer using saliva samples. BACKGROUND [0002] [0001] Head and neck cancer is a common disease. The American Cancer Society, relying on information from the Surveillance, Epidemiology, and End Results (SEER) database, maintained by the National Cancer Institute (NCI), determined that early detection of oral cavity and oropharyngeal cancer improves patient survival rates (https://www.cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/detection-diagnosis- staging/survival-rates.html). Also, the American Dental Association recognizes saliva as a biofluid for diagnostic purposes, including for evaluating the risk of head and neck cancer (https://www.ada.org/resources/research/science-and-research-institute/oral-health- topics/salivary-diagnostics). [0003] The majority of head and neck cancers histologically belong to the squamous cell type and hence are categorized as Head and Neck Squamous Cell Carcinoma (HNSCC). HNSCC is the sixth most common cancer world-wide and the third most common in the developing world. The biological mechanisms behind HNSCC are unknown and there are few, if any, biomarkers that provide a reliable indication of this condition. Still, it would be helpful for individuals having susceptibility to HNSCC to adjust their lifestyle so as to avoid triggering an onset of symptoms and/or promoting further progression of the disease. Thus, there is a need to develop and evaluate improved biomarkers for HNSCC. SUMMARY [0004] The terms “invention,” “the invention,” “this invention” and “the present invention,” as well as “disclosure,” “this disclosure,” and “the present disclosure” as used in this document, are intended to refer broadly to all of the subject matter of this patent application and the claims below. Statements containing these terms should be understood not to limit the subject matter described herein or to limit the meaning or scope of the patent claims below. Covered embodiments of the invention are defined by the claims and the specification, not this summary. This summary is a high-level overview of various aspects of the invention and introduces some of the concepts that are described and illustrated in the present document and the accompanying figures. This summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to be used in isolation to determine the scope of the claimed subject matter. The subject matter should be understood by reference to appropriate portions of the entire specification, any or all figures and each claim. Some of the exemplary embodiments of the present invention are discussed below. [0005] Disclosed are methods, compositions and systems to detect head and neck cancer in a subject using a saliva sample. The disclosed methods, compositions and systems may be embodied in a variety of ways. [0006] For example, in certain embodiments the method may comprise measuring the presence and/or amount of a biomarker associated with Head and Neck Squamous Cell Carcinoma (HNSCC) in an individual comprising the steps of (a) obtaining a saliva sample from the individual; and (b) measuring in the saliva sample an amount of an expression product from at least one gene encoding a biomarker associated with HNSCC, wherein the gene comprises at least one of AIM2, CDSN, INHBA, MMP1, MMP9, or MMP10. Additionally, the expression product of other genes including at least one of MMP13, CRISP3, MUC21, ADAM 12, MMP3 or ISG15 may be measured. In yet other embodiments, disclosed is a composition for detection of a biomarker associated with Head and Neck Squamous Cell Carcinoma (HNSCC) in an individual comprising a reagent for detection of at least one of AIM2, CDSN, INHBA, MMP1, MMP9, or MMP10 in saliva. Additionally, the composition may comprise a reagent for detection of at least one of MMP13, CRISP3, MUC21, ADAM12, MMP3 or ISG15. Also disclosed are systems for performing the methods and/or using the compositions of the invention. BRIEF DESCRIPTION OF THE DRAWINGS [0007] The invention may be better understood by reference to the following non-limiting figures. [0008] FIG. 1 shows an overview of an embodiment of a method of the disclosure, including a range of sample volumes received for use with the method in accordance with an embodiment of the disclosure. [0009] FIG. 2 shows the gender, age, cancer stage, location of tumor and number of saliva samples (“Total Number”) in accordance with an embodiment of the disclosure. [0010] FIG. 3 shows a random forest analysis to identify and rank differentially expressed genes to differentiate HNC from non-cancer samples using the RNASeq dataset showing the top 10 candidate genes. [0011] FIG. 4 shows a random forest analysis to identify and rank additional differentially expressed genes to differentiate HNC from non-