Method for the in vitro diagnosis of bronchopulmonary carcinoma by detection of major alternative transcripts of the klk8 gene encoding kallicrein 8 and use thereof for prognosticating survival

• US 20100255466A1
• Filed: 09/27/2007
• Published: 10/07/2010
• Est. Priority Date: 09/28/2006
• Status: Active Grant

• Current Assignee: Biomerieux B.V. (Compagnie Merieux Alliance SAS), Université François Rabelais de Tours
• Original Assignee: Biomerieux B.V. (Compagnie Merieux Alliance SAS), Université François Rabelais de Tours
• Inventors: Ainciburu, Mireille, Planque, Chris, Courty, Yves, Jolivet-Reynaud, Colette
• Granted Patent: US 8,236,506 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12N 9/6421 from mammals
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development

Abstract

The present invention relates to a method for the in vitro diagnosis of bronchopulmonary carcinoma, in particular of non-small cell bronchial carcinoma, characterized in that it comprises the stage of detecting, in a biological sample derived from a patient suspected to be suffering from said bronchopulmonary carcinoma, at least one of the major alternative transcripts of the KLK8 gene encoding kallikrein 8. This method is particularly useful for the survival prognostication of patients suffering from bronchopulmonary carcinoma.

Claims

1. A method for the in vitro diagnosis of bronchopulmonary carcinoma, in particular of non-small cell bronchial carcinoma, wherein the method comprises the stage of detecting, in a biological sample derived from a patient suspected to be suffering from said bronchopulmonary carcinoma, at least one of major alternative transcripts of the gene KLK8 encoding kallikrein 8.

2. The method as claimed in claim 1, wherein the major alternative transcripts of the 1 KLK8 gene are selected from the transcripts NT3 and NT4.

3. The method as claimed in claim 1, wherein stages consisting in:

i) determining the quantity of major alternative transcript in the biological sample,

ii) comparing the quantity of major alternative transcript in the biological sample with a predetermined threshold value, selected depending on the type of assay utilized and representative of the detection limit of the pathology and

iii) establishing the diagnosis, are implemented.

4. The method as claimed in claim 1, wherein the method also comprises the stage of detecting at least one other transcript of the KLK8 gene.

5. The method as claimed in claim 4, wherein at least one other transcript of the KLK8 gene is the transcript encoding kallikrein KLK8 also called NT1.

6. The method as claimed in claim 4, wherein at least one other transcript of the KLK8 gene is an alternative transcript.

7. The method as claimed in claim 6, wherein the alternative transcript or transcripts are selected from NT2, NT3, NT4, NT5 and NT6.

8. The method as claimed in claim 4, wherein stages consisting in:

i) determining the quantity of major alternative transcript of the KLK8 gene and the quantity of the other transcript of the gene KLK8 in the same biological sample, and

ii) comparing the quantity obtained with a predetermined threshold value, selected depending on the type of assay utilized and representative of the detection limit of the pathology and

iii) establishing the diagnosis, are implemented.

9. The method as claimed in claim 1, wherein the method also comprises the stage of detecting at least one transcript of a gene encoding another kallikrein.

10. The method as claimed in claim 9, wherein stages consisting in:

i) determining the quantity of major alternative transcript of the gene KLK8 and possibly of the other transcript of the gene KLK8 in the biological sample Q1,

ii) determining the quantity of the transcript of the gene encoding the other kallikrein in the same sample Q2,

iii) calculating the ratio Q1/Q2 or Q2/Q1,

iv) comparing said ratio with a predetermined threshold value, selected depending on the type of assay utilized and representative of the detection limit of the pathology and

v) establishing the diagnosis, are implemented.

11. The method as claimed in claim 1, wherein the method also comprises the stage of detecting at least one transcript of another gene expressed in the lung which is not a gene encoding a kallikrein.

12. The method as claimed in claim 11, wherein stages consisting in:

i) determining the quantity of major alternative transcript of the KLK8 gene in the biological sample Q1,

ii) determining the quantity of the transcript of the other gene expressed in the lung in the same sample Q3,

iii) calculating the ratio Q1/Q3 or Q3/Q1,

iv) comparing said ratio with a predetermined threshold value, selected depending on the type of assay utilized and representative of the detection limit of the pathology and

v) establishing the diagnosis, are implemented.

13. Utilization of the method as claimed in claim 1 in the survival prognostication of patients suffering from bronchopulmonary carcinoma.

14. Utilization of a diagnostic kit containing binding partners of the major alternative transcripts of the KLK8 gene, preferably nucleic acid probes or amplification primers for the implementation of the process as described in claim 1.

15. An alternative transcript NT5 of the KLK8 gene encoding kallikrein 8, wherein it has the sequence SEQ ID N^o 7.

16. An alternative transcript NT6 of the KLK8 gene encoding kallikrein 8, wherein it has the sequence SEQ ID N^o 8.