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Methods and kits for diagnosing the prognosis of cancer patients

a cancer patient and prognosis technology, applied in the field of cancer patient prognosis diagnosis methods, can solve the problems of warranted aggressive treatment, and achieve the effects of less aggressive treatment regimen, high capacity for reconstituting, and good prognosis

Inactive Publication Date: 2016-08-04
NEW YORK UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a method for predicting the prognosis of a cancer patient by analyzing the expression levels of genes that are uniquely up-regulated in adult stem cells and fetal stem cells of the tissue where the tumor is found. By measuring the expression levels of these genes in the tumor cells, a good or bad prognosis can be determined, indicating the aggressiveness of treatment needed. The method can be used with various types of cancer, such as prostate, breast, brain, and hematopoietic tumors. The genes analyzed include JUNB, KLF4, FOXH1, FOS, CLDN4, PADI4, B3GNT5, CDC7, CBR3, and ATF3. The expression levels of these genes are compared to normal tissue or other patients' tumor samples to determine the prognosis.

Problems solved by technology

Furthermore, down-regulation of the genes found to be uniquely up-regulated in adult stem cells is also likely to be an indication of poor prognosis, thereby indicating that more aggressive treatment would be warranted.

Method used

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  • Methods and kits for diagnosing the prognosis of cancer patients
  • Methods and kits for diagnosing the prognosis of cancer patients
  • Methods and kits for diagnosing the prognosis of cancer patients

Examples

Experimental program
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Effect test

example 1

KLF4 and JUNB Inhibit Growth and Impede Transformation of Primitive Primary Murine Prostate Cells

[0150]Compared to non-stem cells, adult prostate stem cells (APSCs) express 29-fold more KLF4 and 5-fold more JUNB, both predictors of good prognosis. ShRNA-lentivirus knockdown (KD) of KLF4 or JUNB in primary proximal cells reduced KLF4 by 91%, and JUNB by 80%. Reduction in the expression of these two genes increased stem cell number and their self-renewal as determined by the percent of cells that formed ducts in 3D-collagen gels (FIG. 16, left panel), their size (1.8- and 3.1-fold for KLF4 and JUNB KD, respectively), and their ability to reconstitute sub-renal capsule (RC) prostate tissue (1.4 fold, p<0.03 and 2.3 fold, p<0.04 for KLF4 and JUNB KD, respectively). These effects were even more pronounced when KLF4 or JUNB were knocked down and the cells were simultaneously transformed by co-infection with RFP-active-AKT-expressing lenti-constructs (FIG. 16, right panel), a pathway activ...

example 2

KLF4 and JUNB Inhibit Growth and Impede Transformation of Stable Murine and Human Prostate Cell Lines

[0151]To establish cell lines to be used as models for testing the role of KLF4 and JUNB, a stable cell line was isolated from a tumor derived from murine Sca-1high stem cells that had been transformed by AKT. Stable AKT / KLF4 KD, AKT / JUNB KD and control cell lines were then generated by infecting cells with sh-lentivirus (reduction of the target genes 87-95%). KLF4 KD (76% reduction) and control lines were also generated using a murine prostate stem cell line, WFU (Barclay et al. “Characterization of adult prostatic progenitor / stem cells exhibiting self-renewal and multilineage differentiation,”Stem Cells 26(3):600-610 (2008); Barclay and Cramer. “Culture of mouse prostatic epithelial cells from genetically engineered mice,”Prostate 63(3):291-298 (2005)).

[0152]In addition, stable KLF4 KD (83% reduction) was generated in a human prostate stem cell line, WPE (Tokar et al. “Stem / progeni...

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Abstract

The prognosis of a cancer patient can be determined by analyzing the modulation of expression of specified genes in the tumor tissue. Genes uniquely up-regulated in adult stem cells that can reconstitute the tissue of the tumor are analyzed for up-regulation in the patient's tumor. Up-regulation of a plurality of such genes in the tumor is an indication of good prognosis. Genes uniquely up-regulated in fetal stem cells are analyzed for up-regulation in the patient's tumor. Up-regulation of a plurality of such genes in the tumor are an indication of a poor prognosis. Specific genes are disclosed, the modulation of which, in a patient's prostate cancer tumor, will serve as an indication of prognosis. Patients with a good prognosis are subjected to watchful waiting. Patients with a poor prognosis are aggressively treated. Kits are provided containing a set of affinity reagents that specifically detect expression of the various genes.

Description

[0001]This invention was made with government support under Grant No. 1 US1 RR029893 awarded by National Center for Research Resources, National Institutes of Health, DHHS, Grant No. RO1 CA132641 from the National Cancer Institute, National Institutes of Health, DHHS, and Grant UL1 TR000038 from the National Center for Advancing Translational Sciences of the National Institutes of Health. The government has certain rights in the invention.FIELD OF THE INVENTION[0002]The present invention relates generally to methods for diagnosing the prognosis of cancer patients, and more particularly to the analysis of uniquely up-regulated adult stem cell genes and uniquely up-regulated fetal stem cell genes in the tumor cells of the patient. The presence in the patient's tumor cells of a significant number of uniquely up-regulated adult stem cell genes (adult stem cells have a signature of quiescence), in stem cells having a high capacity to reconstitute the normal tissue from which the tumor or...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68G01N33/574
CPCC12Q1/6886G01N33/6893G01N33/57484C12Q2600/158G01N2800/52G01N2800/60C12Q2600/118G01N33/57434
Inventor WILSON, ELAINE LYNETTEOSSOWSKI, LILIANASMITH, PHILLIP ROSS
Owner NEW YORK UNIV
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