Methods for diagnosis and prognosis of epithelial cancers

Abstract

The present invention is based on the discovery that three proteins, Cystatin B, Chaperonin 10, and Profilin are present in the urine of patients with bladder cancer, a cancer of epithelial origin. Accordingly, the present invention is directed to methods for prognostic evaluation of cancers of epithelial origin and to methods for facilitating diagnosis of cancers of epithelial origin by monitoring the presence of these markers in biological samples. The invention is also directed to markers for therapeutic efficacy.

1 . A method for facilitating the diagnosis of a patient for a cancer of epithelial origin comprising:
 a. obtaining a biological sample from the patient; and   b. detecting the presence or absence of at least one epithelial cancer biomarker in the biological sample,   wherein the presence of at least one epithelial cancer biomarker is indicative of cancer of epithelial origin, and wherein the epithelial cancer biomarker is selected from the group consisting of Cystatin B, Chaperonin 10, and Profilin.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the cancer of epithelial origin is selected from the group consisting of breast cancer, basal cell carcinoma, adenocarcinoma, gastrointestinal cancer, lip cancer, mouth cancer, esophageal cancer, small bowel cancer, stomach cancer, colon cancer, liver cancer, bladder cancer, pancreas cancer, ovary cancer, cervical cancer, lung cancer, skin cancer, prostate cancer, and renal cell carcinoma. 
     
     
         4 . A method for facilitating the diagnosis of bladder cancer in a patient comprising:
 a. obtaining a biological sample from the patient; and   b. detecting the presence or absence of Cystatin B in the biological sample, wherein the presence of Cystatin B epithelial cancer biomarker is indicative of bladder cancer.   
     
     
         5 .- 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the biological sample is urine. 
     
     
         8 . The method of  claim 1  wherein the presence or absence of at least one epithelial cancer biomarker or Cystatin B is detected using an antibody-based binding moiety which specifically binds to at least one epithelial cancer biomarker or to Cystatin B. 
     
     
         9 . The method according to  claim 8  wherein the antibody-based binding moiety is labeled with a detectable label. 
     
     
         10 . The method according to  claim 9  wherein the label is selected from the group consisting of a radioactive label, a hapten label, a fluorescent label, and an enzymatic label. 
     
     
         11 . The method according to  claim 8  wherein the antibody-based binding moiety is an antibody. 
     
     
         12 .- 23 . (canceled) 
     
     
         24 . A method for assessment of a cancer of epithelial origin, the method comprising:
 (a) assaying for cystatin B in a sample obtained from a subject; and   (b) determining whether cystatin B is present at a level higher than a predetermined level, thereby indicating whether the subject is at an increased risk of cancer progression.   
     
     
         25 . The method of  claim 24  wherein the sample is selected from the group consisting of a urine, blood, serum, plasma, stool, sputum, cerebrospinal fluid, nipple aspirate, and tissue sample. 
     
     
         26 . The method of  claim 24  wherein the sample is a urine sample. 
     
     
         27 . The method of  claim 24  wherein the cancer of epithelial origin is selected from the group consisting of bladder cancer, breast cancer, basal cell carcinoma, adenocarcinoma, gastrointestinal cancer, lip cancer, mouth cancer, esophageal cancer, small bowel cancer, stomach cancer, colon cancer, liver cancer, pancreas cancer, ovary cancer, cervical cancer, lung cancer, skin cancer, prostate cancer, and renal cell carcinoma. 
     
     
         28 . The method of  claim 24  wherein the cancer of epithelial origin is bladder cancer. 
     
     
         29 . The method of  claim 24  wherein the predetermined level is based on the level of cystatin B normally found in biological samples of healthy subjects. 
     
     
         30 . The method of  claim 24  wherein the predetermined level is based on a prior measurement of the subject's cystatin B level. 
     
     
         31 . The method of  claim 24  wherein the predetermined level is based on the subject's cystatin B level prior to treatment. 
     
     
         32 . The method of  claim 24  wherein the subject's cystatin B level is monitored over time. 
     
     
         33 . The method of  claim 24  wherein the cancer progression is a recurrence of cancer, an increase of metastatic activity, or a progression in cancer grade or stage. 
     
     
         34 .- 35 . (canceled) 
     
     
         36 . The method of  claim 24  wherein cystatin B protein is assayed. 
     
     
         37 . The method of  claim 36  wherein the cystatin B protein is assayed for by an immunoassay or by mass spectrometry.