Prognosis and Therapy Predictive Markers and Methods of Use

Abstract

Disclosed is a set of genes differentially expressed in chemotherapy and radiation resistant tumors useful in predicting response to therapy and assessing risk of local-regional failure, survival and metastasis in cancer patients. Also disclosed are methods for characterizing tumors according to gene expression and kits for use in the methods of the invention.

1 . A method of characterizing a tumor from a patient comprising detecting expression of at least one IRDS marker by the tumor. 
     
     
         2 . The method of  claim 1 , wherein the expression of two or more markers selected from the group of markers listed in Table 1 is detected. 
     
     
         3 . The method of  claim 1 , wherein the expression of at least three, four, five or six markers selected from the group of markers listed in Table 1 is detected. 
     
     
         4 . The method of  claim 1 , wherein the expression of at least seven markers selected from the group of markers listed in Table 1 is detected. 
     
     
         5 . The method of  claim 1 , wherein the tumor is selected from the group consisting of lung cancer, prostate cancer, testicular cancer, brain cancer, skin cancer, colon cancer, rectal cancer, gastric cancer, esophageal cancer, tracheal cancer, head and neck cancer, pancreatic cancer, liver cancer, breast cancer, ovarian cancer, lymphoid cancer, kidney cancer, cervical cancer, bone cancer, vulvar cancer and melanoma. 
     
     
         6 . The method of  claim 1  further comprising determining the status of a prognosis factor. 
     
     
         7 . The method of  claim 6  wherein the prognosis factor comprises age, grade of tumor, tumor size, lymph node status or distant metastasis. 
     
     
         8 . The method of  claim 6  wherein the prognosis factor comprises expression of at least one marker from the NKI70 gene signature. 
     
     
         9 . The method of  claim 6  wherein the prognosis factor comprises expression of at least one lung metastatic marker. 
     
     
         10 . The method of  claim 1 , further comprising analyzing the expression of the at least one marker to determine an IRDS status of the tumor. 
     
     
         11 . The method of  claim 10 , wherein the IRDS status is assigned by calculating an IRDS score. 
     
     
         12 . The method of  claim 11 , wherein an IRDS score of two or higher is predictive of adjuvant resistant cancer status. 
     
     
         13 . The method of  claim 1 , further comprising using the expression of the IRDS marker to predict tumor response to a chemotherapeutic agent or radiation administered to the patient. 
     
     
         14 . The method of  claim 13 , wherein the expression of the IRDS marker is indicative of tumor resistance to the chemotherapeutic agent or radiation. 
     
     
         15 . The method of  claim 13  wherein the expression of the IRDS marker is indicative of tumor sensitivity to the chemotherapeutic agent or radiation. 
     
     
         16 . The method of  claim 13 , wherein the chemotherapeutic agent is a DNA damaging agent. 
     
     
         17 . The method of  claim 13 , wherein the chemotherapeutic agent is a direct or indirect modulator of an interferon pathway. 
     
     
         18 . The method of  claim 13 , further comprising determining a cancer patient treatment protocol based on the predicted tumor response. 
     
     
         19 . The method of  claim 1 , wherein the IRDS expression is used to determine a prognosis for the patient. 
     
     
         20 . The method of  claim 19 , wherein the prognosis comprises relative survival rate. 
     
     
         21 . The method of  claim 19 , wherein the prognosis comprises relative risk of metastasis. 
     
     
         22 . The method of  claim 19 , wherein the prognosis comprises relative risk of local-regional failure. 
     
     
         23 . A kit for performing the method of  claim 1  comprising a probe for detecting expression of the IRDS marker. 
     
     
         24 . The kit of  claim 23 , wherein the probe comprises an antibody to an epitope of a protein encoded by an IRDS marker selected from the group of markers listed in Table 1. 
     
     
         25 . The kit of  claim 23 , wherein the probe comprises at least one primer pair for amplifying at least one IRDS marker selected from the group of markers listed in Table 1. 
     
     
         26 . The kit of  claim 23 , wherein the probe comprises an oligonucleotide complementary to at least a portion of at least one IRDS marker selected from the group of markers listed in Table 1. 
     
     
         27 . The kit of  claim 25 , wherein the oligonucleotide is provided as a microarray. 
     
     
         28 . A method of identifying a gene signature marker the expression of which correlates with clinical outcome comprising:
 a) developing a radiation or chemotherapeutic resistant cell line from a radiation or chemotherapeutic sensitive cell line;   b) identifying genes differentially expressed in the resistant cell line relative to the sensitive cell line, the differentially expressed genes forming a resistance gene signature;   c) determining the resistance gene signature status of tumors from a population of humans; and   d) correlating the resistance gene status of step c) with clinical outcome.