Prediction of Likelihood of Cancer Recurrence

Abstract

The present invention provides gene sets the expression of which is important in the diagnosis and/or prognosis of cancer, in particular of breast cancer.

1 . A method of predicting the likelihood of long-term survival of a cancer patient without the recurrence of cancer, comprising determining the expression level of one or more prognostic RNA transcripts or their expression products in a cancer cell obtained from said patient, normalized against the expression level of all RNA transcripts or their products in said cancer cell, or of a reference set of RNA transcripts or their expression products, wherein the prognostic RNA transcript is the transcript of one or more genes selected from the group consisting of B_Catenin; BAG1; BIN1; BUB1; C20_orfl; CCNB1; CCNE2; CDC20; CDH1; CEGP1; CIAP1; cMYC; CTSL2; DKFZp586M07; DR5; EpCAM; EstR1; FOXM1; GRB7; GSTM1; GSTM3; HER2; HNRPAB; ID1; IGF1R; ITGA7; Ki — 67; KNSL2; LMNB1; MCM2; MELK; MMP12; MMP9; MYBL2; NEK2; NME1; NPD009; PCNA; PR; PREP; PTTG1; RPLPO; Src; STK15; STMY3; SURV; TFRC; TOP2A; and TS;
 wherein expression of one or more of BUB1; C20_orfl; CCNB1; CCNE2; CDC20; CDH1; CTSL2; EpCAM; FOXM1; GRB7; HER2; HNRPAB; Ki — 67; KNSL2; LMNB1; MCM2; MELK; MMP12; MMP9; MYBL2; NEK2; NME1; PCNA; PREP; PTTG1; Src; STK15; STMY3; SURV; TFRC; TOP2A; and TS indicates a decreased likelihood of long-term survival without cancer recurrence; and   the expression of one or more of BAG1; BCatenin; BIN1; CEGP1; CIAP1; cMYC; DKFZp586M07; DR5; EstR1; GSTM1; GSTM3; ID1; IGF1R; ITGA7; NPD009; PR; and RPLPO indicates an increased likelihood of long-term survival without cancer recurrence.   
     
     
         2 . The method of  claim 1  comprising determining the expression level of at least two of said prognostic RNA transcripts or their expression products. 
     
     
         3 . The method of  claim 1  comprising determining the expression level of at least 5 of said prognostic RNA transcripts or their expression products. 
     
     
         4 . The method of  claim 1  comprising determining the expression level of at least 10 of said prognostic RNA transcripts or their expression products. 
     
     
         5 . The method of  claim 1  comprising determining the expression level of at least 15 of said prognostic transcripts of their expression products. 
     
     
         6 . The method of  claim 1  wherein said cancer is breast cancer. 
     
     
         7 . The method of  claim 6  wherein said cancer is node negative, ER positive breast cancer. 
     
     
         8 . The method of  claim 1  wherein said cancer is ovarian cancer. 
     
     
         9 . The method of  claim 1  wherein the expression level of one or more prognostic RNA transcripts is determined. 
     
     
         10 . The method of  claim 1  wherein said RNA comprises intronic RNA. 
     
     
         11 . The method of  claim 1  comprising determining the expression level of one or more prognostic RNA transcripts or their expression products of one or more genes selected from the group consisting of MMP9, GSTM1, MELK, PR, DKFZp586M07, GSTM3, CDC20, CCNB1, STMY3, GRB7, MYBL2, CEGP1, SURV, LMNB1, CTSL2, PTTG1, BAG1, KNSL2, CIAP1, PREP, NEK2, EpCAM, PCNA, C20_orfl, ITGA7, ID1 B_Catenin, EstR1, CDH1, TS HER2, and cMYC,
 wherein expression of one or more of C20_orfl; CCNB1; CDC20; CDH1; CTSL2; EpCAM; GRB7; HER2; KNSL2; LMNB1; MCM2; MMP9; MYBL2; NEK2; PCNA; PREP; PTTG1; STMY3; SURV; TS; and MELK indicates a decreased likelihood of long-term survival without cancer recurrence; and   expression of one or more of BAG1; BCatenin; CEGP1; CIAP1; cMYC; DKFZp586M07; EstR1; GSTM1; GSTM3; ID1; ITGA7; and PR indicates an increased likelihood of long-term survival without cancer recurrence.   
     
     
         12 . The method of  claim 1  comprising determining the expression level of one or more prognostic RNA transcripts or their expression products of one or more genes selected from the group consisting of GRB7, SURV, PR, LMNB1, MYBL2, HER2, GSTM1, MELK, S20_orfl, PTTG1, BUB1, CDC20, CCNB1, STMY3, KNSL2, CTSL2, MCM2, NEK2, DR5, Ki — 67, CCNE2, TOP2A, PCNA, PREP, FOXM1, NME1, CEGP1, BAG1, STK15, HNRPAB, EstR1, MMP9, DKFZp586M07, TS, Src, BIN1, NP009, RPLPO, GSTM3, MMP12, TFRC, and IGF1R,
 wherein expression of one or more of GRB7; SURV; LMNB1; MYBL2; HER2; MELK; C20_orfl; PTTG1; BUB1; CDC20; CCNB1; STMY3; KNSL2; CTSL2; MCM2; NEK2 Ki — 67; CCNE2; TOP2A — 4; PCNA; PREP; FOXM1; NME1; STK15; HNRPAB; MMP9; TS; Src; MMP12; and TFRC indicates a decreased likelihood of long-term survival without cancer recurrence; and   the expression of one or more of PR; GSTM1; DR5; CEGP1; BAG1; EstR1; DKFZp586M07; BIN1; NPD009; RPLPO; GSTM3; IGF1R indicates an increased likelihood of long-term survival without cancer recurrence.   
     
     
         13 . A method of predicting the likelihood of long-term survival of a cancer patient without the recurrence of cancer, comprising determining the expression level of one or more prognostic RNA transcripts or their expression products in a cancer cell obtained from said patient, normalized against the expression level of all RNA transcripts or their products in said cancer cell, or of a reference set of RNA transcripts or their expression products, wherein the prognostic RNA transcript is the transcript of one or more genes selected from the group consisting of GRB7; LMNB1; ER; STMY3; KLK10; PR; KRT5; FGFR1; MCM6; SNRPF,
 wherein expression of one or more of GRB7, LMNB1, STMY3, KLK10, FGFR1, and SNRPF indicates a decreased likelihood or long term survival without cancer recurrence; and the expression of one or more of ER, PR, KRT5 and MCM6 indicates an increased likelihood of long-term survival without cancer recurrence.   
     
     
         14 . The method of  claim 6  wherein said RNA is isolated from a fixed, wax-embedded breast cancer tissue specimen of said patient. 
     
     
         15 . The method of  claim 6  wherein said RNA is isolated from core biopsy tissue or fine needle aspirate cells. 
     
     
         16 . An array comprising polynucleotides hybridizing to two or more of the following genes: B_Catenin; BAG1; BIN1; BUB1; C20_orfl; CCNB1; CCNE2; CDC20; CDH1; CEGP1; CIAP1; cMYC; CTSL2; DKFZp586M07; DR5; EpCAM; EstR1; FOXM1; GRB7; GSTM1; GSTM3; HER2; HNRPAB; ID1; IGF1R; ITGA7; Ki — 67; KNSL2; LMNB1; MCM2; MELK; MMP12; MMP9; MYBL2; NEK2; NME1; NPD009; PCNA; PR; PREP; PTTG1; RPLPO; Src; STK15; STMY3; SURV; TFRC; TOP2A; and TS, immobilized on a solid surface. 
     
     
         17 . The array of  claim 16  comprising polynucleotides hybridizing to two or more of the following genes: MMP9, GSTM1, MELK, PR, DKFZp586M07, GSTM3, CDC20, CCNB1, STMY3, GRB7, MYBL2, CEGP1, SURV, LMNB1, CTSL2, PTTG1, BAG1, KNSL2, CIAP1, PREP, NEK2, EpCAM, PCNA, C20_orfl, ITGA7, ID1 B_Catenin, EstR1, CDH1, TS HER2, and cMYC. 
     
     
         18 . The array of  claim 16  comprising polynucleotides hybridizing to two or more of the following genes: GRB7, SURV, PR, LMNB1, MYBL2, HER2, GSTM1, MELK, S20_orfl, PTTG1, BUB1, CDC20, CCNB1, STMY3, KNSL2, CTSL2, MCM2, NEK2, DR5, Ki — 67, CCNE2, TOP2A, PCNA, PREP, FOXM1, NME1, CEGP1, BAG1, STK15, HNRPAB, EstR1, MMP9, DKFZp586M07, TS, Src, BIN1, NP009, RPLPO, GSTM3, MMP12, TFRC, and IGF1R. 
     
     
         19 . The array of  claim 16  comprising polynucleotides hybridizing to at least 3 of said genes. 
     
     
         20 . The array of  claim 16  comprising polynucleotides hybridizing to at least 5 of said genes. 
     
     
         21 - 40 . (canceled)