Compositions and methods for prognosis and therapy of liver cancer

Inactive Publication Date: 2005-04-28
THE UNIVERSITY OF HONG KONG
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Benefits of technology

[0010] This invention further provides a method for determining the prognosis of a subject afflicted with hepatocellular carcinoma (HCC), comprising: (a) obtaining a tumor sample from the subject; (b) determining the level of CLDN10 nucleic acid transcript in the tumor sample; (c) comparing the level of CLDN10 nucleic acid transcript from step (b) with the level of CLDN10 nucleic acid transcript in the normal tissue sample, whereby a higher level of CLDN10 nucleic acid transcript in step (b) indicates a poor prognosis.
[0011] This invention also provides a method for determining the prognosis of a subject afflicted with hepatocellular carcinoma (HCC), comprising: (a) obtaining a tumor sample from the subject; (b) determining the level of AA454543 nucleic acid transcript in the tumor sample; (c) comparing the level of AA454543 nucleic acid transcript from step (b) with the level of AA454543 nucleic acid transcript in the normal tissue sample, whereby a higher level of AA454543 nucleic acid transcript in step (b) indicates a poor prognosis.
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Problems solved by technology

However, conventional clinico-pathological parameters have limited predictive power,

Method used

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  • Compositions and methods for prognosis and therapy of liver cancer
  • Compositions and methods for prognosis and therapy of liver cancer
  • Compositions and methods for prognosis and therapy of liver cancer

Examples

Experimental program
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example iv

Synopsis:

[0118] Dynein, axonemal, light intermediate polypeptide 1 (DNALI1) expression was found to significantly associate with disease recurrence (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.1-2.6, P=0.014) as shown in our earlier genome-wide expression study by cDNA microarray approach on hepatocellular carcinoma (HCC). This study was performed on an independent sample set (n=50) and employed quantitative RT-PCR to examine the DNALI1 transcript level. The association of higher DNALI1 expression level with early disease recurrence was again confirmed. Our preliminary sequencing study indicated that DNALI1 had a polymorphism at nucleotide 194 (codon 65), which either harbored the C-allele (GCA, alanine) or T-allele (GTA, valine). We then further examined the blood samples of the patients for the nucleotide 194 polymorphism (n=50, paralleled samples where the HCCs had quantitative RT-PCR data). The tumor DNALI1 transcript level was significantly higher in patients with T...

example i

REFERENCES FOR EXAMPLE I

[0119] 1. Pisani, P., Parkin, D. M., Bray, F. & Ferlay, J. “Estimates of the Worldwide Mortality from 25 Cancers in 1990”, Int. J. Cancer 83, 18-29 (1999). [0120] 2. El-Serag, H. B. & Mason, A. C., “Rising Incidence of Hepatocellular Carcinoma in the United States”, N. Engl. J. Med. 340, 745-750 (1999). [0121] 3. Taylor-Robinson, S. D., Foster, G. R., Arora, S., Hargreaves, S. & Thomas, H. C., “Increase in Primary Liver Cancer in the UK, 1979-94”, Lancet 350:1142-1143 (1997). [0122] 4. Okuda, K., Fujimoto, I., Hanai, A. & Urano, Y., “Changing Incidence of Hepatocellular Carcinoma in Japan,”Cancer Res. 47, 4967-4972 (1987). [0123] 5. Tang, Z. Y., “Hepatocellular Carcinoma”, J. Gastroenterol. Hepatol. 15 Suppl, G1-7 (2000). [0124] 6. Ng, I. O., Lai, E. C., Fan, S. T., Ng, M. M. & So, M. K., “Prognostic Significance of Pathologic Features of Hepatocellular Carcinoma. A Multivariate Analysis of 278 Patients”, Cancer 76, 2443-2448 (1995). [0125] 7. Ng, I. O., Poon...

example ii

REFERENCES FOR EXAMPLE II

[0164] 1. Pisani, P., Parkin, D. M., Bray, F., and Ferlay, J. Estimates of the worldwide mortality from 25 cancers in 1990. Int. J. Cancer, 83:18-29, 1999. [0165] 2. El-Serag, H. B., and Mason, A. C. Rising incidence of hepatocellular carcinoma in the United States. N. Engl. J. Med. 340:745-750, 1999. [0166] 3. Taylor-Robinson, S. D., Foster, G. R., Arora, S., Hargreaves, S., and Thomas, H. C. Increase in primary liver cancer in the UK, 1979-94. Lancet, 350:1142-1143, 1997. [0167] 4. Okuda, K., Fujimoto, I., Hanai, A., and Urano, Y. Changing incidence of hepatocellular carcinoma in Japan. Cancer Res., 47:4967-4972, 1987. [0168] 5. Tang Z Y. Hepatocellular carcinoma. J. Gastroenterol. Hepatol., 15 Suppl:G1-G7, 2000. [0169] 6. Ng, I. O., Lai, E. C., Fan, S. T., Ng, M. M., and So, M. K. Prognostic significance of pathologic features of hepatocellular carcinoma. A multivariate analysis of 278 patients. Cancer, 76:2443-2448, 1995. [0170] 7. Poon, R. T., Fan, S. T...

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Abstract

This invention provides a composition comprising the following polynucleotide probes: IL7R (AA485865), NDRG1 (AA486403), EST1 (H50345), TRPC1 (AA017132), GFRA1 (AA512935), EST2 (AA454543), CLDN10 (R54559), DNALI1 (R93087), RBP5 (AA453198), EST3 (AA621761), EST4 (N63706), PCOLCE (AA670200), TDO2 (T72398), EST5 (T47454), HIST1H2BD (N33927), PXMP2 (N70714), ACAS2 (AA455146), ANAPC7 (T68445), EST6 (AA576580), RBP5 (N92148), ANXA1 (H63077), CKB (AA894557), ITGBL1 (N52533), KPNA2 (AA676460), EST7 (W90740) and MEG3 (W85841). This invention further provides methods for determining the likelihood of recurrence of hepatocellular carcinoma (HCC) in a subject afflicted with HCC, for determining the likelihood of death of a subject afflicted with HCC or for determining whether to administer adjuvant therapy.

Description

[0001] This application claims priority of provisional application U.S. Ser. No. 60 / 495,081, filed Aug. 13, 2003, and provisional application U.S. Ser. No. 60 / 500,844, filed Sep. 4, 2003, the contents of both provisional application being incorporated herein by reference.[0002] Throughout this application, various publications are referenced. Full citations for these publications may be found immediately preceding the claims. The disclosures of these publications are hereby incorporated by reference into this application in order to more fully describe the state of the art as of the date of the invention described and claimed herein. BACKGROUND OF THE INVENTION [0003] Hepatocellular carcinoma (HCC) is a common lethal malignancy and among the five leading causes of cancer death worldwide. The incidence is rising in the United States, UK and Japan. Liver cancer is the second major cause of cancer death in China. Epidemiological studies have shown that hepatitis B and C virus infection...

Claims

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Application Information

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IPC IPC(8): C07H21/00C12Q1/68
CPCC07H21/00C12Q1/6886C12Q2600/16C12Q2600/118C12Q2600/158C12Q2600/106
Inventor CHEUNG, SIUFAN, SHEUNG
Owner THE UNIVERSITY OF HONG KONG
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