Gene expression-based biomarker for the detection and monitoring of bronchial premalignant lesions

Abstract

Disclosed herein are assays and methods for the identification of premalignant lesions, as well as methods of determining the likelihood that such premalignant lesions will progress to lung cancer. Also disclosed are methods and assays that are useful for monitoring the progression of premalignant lesions to lung cancer. The assays and methods disclosed herein provide minimally invasive means of accurately detecting and monitoring the presence or absence of premalignant lesions, thus providing novel insights into the earliest stages of lung cancer and facilitating early detection and early intervention.

1 .- 18 . (canceled) 
     
     
         19 . A method of processing a sample from a subject suspected of having a premalignant bronchial lesion comprising the steps of: (a) providing a biological sample from the mouth or nose of the subject or from a brushing of the bronchi walls of the subject; and (b) measuring the expression of two or more genes in the sample by northern-blot hybridization, a ribonuclease protection assay, or a reverse transcriptase polymerase chain reaction (RT-PCR) method, wherein the two or more genes are genes involved in an oxidative phosphorylation (OXPHOS), electron transport chain (ETC), or mitochondrial protein transport pathway. 
     
     
         20 . The method of  claim 19 , wherein the expression of at least five genes involved in an oxidative phosphorylation (OXPHOS), electron transport chain (ETC), or mitochondrial protein transport pathway are measured. 
     
     
         21 . The method of  claim 19 , wherein the expression in the sample of at least twenty genes are measured. 
     
     
         22 . The method of  claim 19 , wherein the two or more genes comprise cDNA. 
     
     
         23 . The method of  claim 19 , wherein the expression of two or more genes in the sample is measured by an RT-PCR method. 
     
     
         24 . The method of  claim 19 , wherein the biological sample is obtained from the mouth of the subject. 
     
     
         25 . The method of  claim 19 , wherein the subject has a positive result in an imaging study of a premalignant bronchial lesion. 
     
     
         26 . The method of  claim 19 , wherein the subject has previously been diagnosed with a lung, bronchus, head/neck, and/or esophagus cancer but has no current evidence of the cancer. 
     
     
         27 . The method of  claim 19 , wherein the subject is a current smoker or a former smoker with 20+ pack years. 
     
     
         28 . The method of  claim 27 , wherein the subject is at least 50 years old. 
     
     
         29 . The method of  claim 19 , wherein the subject has emphysema, chronic bronchitis, chronic obstructive pulmonary disease, an occupationally related asbestos disease, or a family history of lung cancer in a first degree relative. 
     
     
         30 . The method of  claim 29 , wherein the subject is at least 50 years old.