Method of predicting risk of recurrence of cancer

Abstract

A method for predicting risk of recurrence of cancer in an individual with cancer, the method comprising a step of assaying a cancer sample from the individual for positive expression of at least two genes or proteins encoded by those genes selected from the group consisting of FOXM1, UHRF1, PTTG1, E2F1, MYBL2, HMGB2, ATAD2, E2F8, ZNF367 and TCF19, wherein positive expression of the at least two genes correlates with increased risk of recurrence of cancer compared with an individual who does not exhibit positive expression of the at least two genes or proteins encoded by those genes.

1 .- 23 . (canceled) 
     
     
         24 . A method of treating cancer in a patient in need thereof, the method comprising:
 assaying a cancer sample from the patient for positive expression of at least FOXM1, PTTG1, and ZNF367;   detecting positive expression of at least FOXM1; PTTG1; and ZNF367; and   administering a neoadjuvant or an adjuvant therapy or combination of both.   
     
     
         25 . The method according to  claim 24 , wherein the neoadjuvant therapy and adjuvant therapy is an agent selected from the group consisting of: trastuzumab, lapatinib, neratinib, afatinib, pertuzumab, CDK4/6 inhibitors, cyclophosphamide, methotrexate, 5-fluorouracil, gemcitabine, adriamycin (doxorubicin), epirubucin, docetaxel, paclitaxel, capecitabine, and tamoxifen. 
     
     
         26 . The method according to  claim 24 , the method further comprising the step of assaying for the expression of p16 INK4A  gene or a protein encoded by said gene. 
     
     
         27 . The method according to  claim 24 , further comprising assaying the cancer sample from the patient for positive expression of UHRF1, MYBL2, E2F8, HMGB2, ATAD2, E2F1, or TCF19. 
     
     
         28 . The method according to  claim 24 , wherein the cancer is selected from the group consisting of: node-negative, ER-positive breast cancer; early stage, node positive breast cancer; multiple myeloma, prostate cancer, glioblastoma, lymphoma, fibrosarcoma; myxosarcoma; liposarcoma; chondrosarcoma; osteogenic sarcoma; chordoma; angiosarcoma; endotheliosarcoma; lymphangiosarcoma; lymphangioendotheliosarcoma; synovioma; mesothelioma; Ewing's tumour; leiomyosarcoma; rhabdomyosarcoma; colon carcinoma; pancreatic cancer; breast cancer; ovarian cancer; squamous cell carcinoma; basal cell carcinoma; adenocarcinoma; sweat gland carcinoma; sebaceous gland carcinoma; papillary carcinoma; papillary adenocarcinomas; cystadenocarcinoma; medullary carcinoma; bronchogenic carcinoma; renal cell carcinoma; hepatoma; bile duct carcinoma; choriocarcinoma; seminoma; embryonal carcinoma; Wilms' tumour; cervical cancer; uterine cancer; testicular tumour; lung carcinoma; small cell lung carcinoma; bladder carcinoma; epithelial carcinoma; glioma; astrocytoma; medulloblastoma; craniopharyngioma; ependymoma; pinealoma; hemangioblastoma; acoustic neuroma; oligodendroglioma; meningioma; melanoma; retinoblastoma; and leukemia. 
     
     
         29 . A method of treating cancer in a subject in need thereof, the method comprising:
 being provided information comprising an indication of positive expression of at least FOXM1, PTTG1, and ZNF367 in a cancer sample from a subject; and   then administering a neoadjuvant or an adjuvant therapy or combination of both to the subject.   
     
     
         30 . The method according to  claim 29 , wherein the neoadjuvant therapy and adjuvant therapy is an agent selected from the group consisting of: trastuzumab, lapatinib, neratinib, afatinib, pertuzumab, CDK4/6 inhibitors, cyclophosphamide, methotrexate, 5-fluorouracil, gemcitabine, adriamycin (doxorubicin), epirubucin, docetaxel, paclitaxel, capecitabine, and tamoxifen. 
     
     
         31 . The method according to  claim 29 , wherein the subject is further determined to have dysregulated expression of p16 INK4A , in combination with positive expression of the at least three genes. 
     
     
         32 . The method according to  claim 29 , wherein the patient is further determined to have positive expression of UHRF1, MYBL2, E2F8, HMGB2, ATAD2, E2F1, or TCF19. 
     
     
         33 . The method according to  claim 29 , wherein the cancer is selected from the group consisting of: node-negative, ER-positive breast cancer; early stage, node positive breast cancer; multiple myeloma, prostate cancer, glioblastoma, lymphoma, fibrosarcoma; myxosarcoma; liposarcoma; chondrosarcoma; osteogenic sarcoma; chordoma; angiosarcoma; endotheliosarcoma; lymphangiosarcoma; lymphangioendotheliosarcoma; synovioma; mesothelioma; Ewing's tumour; leiomyosarcoma; rhabdomyosarcoma; colon carcinoma; pancreatic cancer; breast cancer; ovarian cancer; squamous cell carcinoma; basal cell carcinoma; adenocarcinoma; sweat gland carcinoma; sebaceous gland carcinoma; papillary carcinoma; papillary adenocarcinomas; cystadenocarcinoma; medullary carcinoma; bronchogenic carcinoma; renal cell carcinoma; hepatoma; bile duct carcinoma; choriocarcinoma; seminoma; embryonal carcinoma; Wilms' tumour; cervical cancer; uterine cancer; testicular tumour; lung carcinoma; small cell lung carcinoma; bladder carcinoma; epithelial carcinoma; glioma; astrocytoma; medulloblastoma; craniopharyngioma; ependymoma; pinealoma; hemangioblastoma; acoustic neuroma; oligodendroglioma; meningioma; melanoma; retinoblastoma; and leukemias. 
     
     
         34 . A method of treating cancer in a subject in need thereof, the method comprising:
 assaying a sample from the subject prior to receiving a neoadjuvant or an adjuvant therapy, or combination of both, for positive expression of at least FOXM1, PTTG1, and ZNF367;   assaying a sample from the subject after receiving the neoadjuvant or the adjuvant therapy, or combination of both, for positive expression of at least FOXM1, PTTG1, and ZNF367;   continuing to administer the neoadjuvant or the adjuvant therapy, or the combination of both, when detecting positive expression of at least FOXM1; PTTG1; and ZNF367 at levels that, when combined, are lower when compared to the levels of expression from the sample assayed prior to receiving the neoadjuvant or the adjuvant therapy, or combination of both;   discontinuing to administer the neoadjuvant or the adjuvant therapy, or the combination of both, when detecting positive expression of at least FOXM1; PTTG1; and ZNF367 at levels, when combined, that are the same or higher when compared to the levels of expression from the sample assayed prior to receiving the neoadjuvant or the adjuvant therapy, or combination of both; or   changing the neoadjuvant or the adjuvant therapy, or the combination of both, when detecting positive expression of at least FOXM1; PTTG1; and ZNF367 at levels, when combined, that are the same or higher when compared to the levels of expression from the sample assayed prior to receiving the neoadjuvant or the adjuvant therapy, or combination of both.   
     
     
         35 . The method according to  claim 34 , wherein the neoadjuvant therapy and adjuvant therapy is an agent selected from the group consisting of: trastuzumab, lapatinib, neratinib, afatinib, pertuzumab, CDK4/6 inhibitors, cyclophosphamide, methotrexate, 5-fluorouracil, gemcitabine, adriamycin (doxorubicin), epirubucin, docetaxel, paclitaxel, capecitabine, and tamoxifen. 
     
     
         36 . The method according to  claim 34 , the method further comprising the step of assaying for the expression of p16 INK4A  gene or a protein encoded by said gene. 
     
     
         37 . The method according to  claim 34 , further comprising assaying the cancer sample from the patient for positive expression of UHRF1, MYBL2, E2F8, HMGB2, ATAD2, E2F1, or TCF19. 
     
     
         38 . The method according to  claim 34 , wherein the cancer is selected from the group consisting of: node-negative, ER-positive breast cancer; early stage, node positive breast cancer; multiple myeloma, prostate cancer, glioblastoma, lymphoma, fibrosarcoma; myxosarcoma; liposarcoma; chondrosarcoma; osteogenic sarcoma; chordoma; angiosarcoma; endotheliosarcoma; lymphangiosarcoma; lymphangioendotheliosarcoma; synovioma; mesothelioma; Ewing's tumour; leiomyosarcoma; rhabdomyosarcoma; colon carcinoma; pancreatic cancer; breast cancer; ovarian cancer; squamous cell carcinoma; basal cell carcinoma; adenocarcinoma; sweat gland carcinoma; sebaceous gland carcinoma; papillary carcinoma; papillary adenocarcinomas; cystadenocarcinoma; medullary carcinoma; bronchogenic carcinoma; renal cell carcinoma; hepatoma; bile duct carcinoma; choriocarcinoma; seminoma; embryonal carcinoma; Wilms' tumour; cervical cancer; uterine cancer; testicular tumour; lung carcinoma; small cell lung carcinoma; bladder carcinoma; epithelial carcinoma; glioma; astrocytoma; medulloblastoma; craniopharyngioma; ependymoma; pinealoma; hemangioblastoma; acoustic neuroma; oligodendroglioma; meningioma; melanoma; retinoblastoma; and leukemias.