Molecular markers for lung and colorectal carcinomas
AssigneeAdvpharma Inc.
InventorsHarn-Jing TERNG, Woan-Jen Lee, Chin-Yu Chen
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Abstract
Molecular markers for lung and colorectal carcinomas and methods of using them in blood sample assays are disclosed. The method comprises measuring the expression of the markers in a blood sample from a subject for detecting the presence and/or severity of lung and/or colorectal cancer, and for monitoring and/or assessing the prognosis of the subject's response to a cancer therapy. Also disclosed are kits for detecting, diagnosing, and/or monitoring lung or colorectal carcinomas.
Claims26
A method for detecting the presence and/or severity of lung and/or colorectal cancer, comprising the steps of:
- (a) obtaining a test sample of bodily fluid comprising a nucleic acid from a subject;
- (b) measuring the expression level of at least one cancer gene marker selected from:
- (i) the group consisting of:
- DUSP6, EIF2S3, GRB2, RNF4, MMD, MCM4, NF1 and MDM2;
- or
- (ii) the group consisting of:
- DUSP6, EIF2S3, MDM2, NF1, MMD, RNF4, GRB2, and EXT2;
- (c) normalizing the expression level of the at least one cancer gene marker to a housekeeping gene;
- (d) applying the normalized expression level of the at least one cancer gene marker to a logistic regression prediction model which calculates the probability of cancer and/or cancer recurrence risk;
- and
- (e) determining the presence and/or severity of lung and/or colorectal cancer based on the calculated probability.
A method for monitoring and/or assessing the prognosis of a patient's response to a cancer therapy, comprising the steps of:
- (a) obtaining samples of bodily fluid comprising a nucleic acid from the patient before and after receiving a cancer therapy for a lung and/or colorectal cancer;
- (b) measuring the expression level of at least one cancer gene marker selected from the group consisting of DUSP6, EIF2S3, GRB2, RNF4, MMD, MCM4, NF1, and MDM2;
- (c) normalizing tile expression level of at least one cancer gene marker to a housekeeping gene;
- (d) applying the normalized expression level of at least one cancer gene marker to a logistic regression prediction model which calculates the probability of cancer and/or cancer recurrence risk;
- and
- (e) evaluating the response by comparing the calculated probabilities from the samples, and thereby monitoring and/or assessing the prognosis of a patient's response to a cancer therapy;
- wherein a decrease in the probability after receiving the cancer therapy is indicative of a positive response to the therapy.
A method for monitoring and/or assessing the prognosis of a patient's response to a cancer therapy, comprising the steps of:
- (a) obtaining a first sample of bodily fluid comprising a nucleic acid from the patient before receiving a cancer therapy for a lung and/or colorectal cancer;
- (b) obtaining a second sample of bodily fluid comprising a nucleic acid from the patient after receiving the therapy;
- (c) measuring the expression level of at least one cancer gene marker selected from the group consisting of DUSP6, EIF2S3, GRB2, RNF4, MMD, MCM4, NF1, MDM2 in the first and second samples;
- and
- (d) comparing the measured expression levels in the first and second samples and thereby monitoring and/or assessing the prognosis of the patient's response to the cancer therapy;
- wherein:
- (i) an increase in the expression level(s) of DUSP6, GRB2, MCM4 and/or NF1 in the second sample as compared to the level(s) of the corresponding gene marker(s) in the first sample is an indication that the subject is at risk of developing lung cancer and/or lung cancer recurrence;
- (ii) an increase in the expression level of MDM2 in the second sample as compared to the level of the corresponding marker in the first sample is an indication that the subject is at risk of lung cancer recurrence;
- and
- (iii) an increase in the expression level of EIF2S3, MMD, and/or RNF4 in the second sample as compared to the level of the corresponding marker(s) in the first sample is an indication that the subject is not at risk of developing lung cancer.
A method for detecting the presence and/or severity of lung and/or colorectal cancer, comprising the steps of:
- (a) obtaining a test sample of bodily fluid comprising a nucleic acid from a subject;
- (b) measuring the expression level of at least one cancer gene marker selected from:
- (i) the group consisting of:
- DUSP6, EIF2S3, GRB2, RNF4, MMD, MCM4, NF1, and MDM2;
- or
- (ii) the group consisting of:
- DUSP6, EIF2S3, MDM2, NF1, MMD, RNF4, GRB2, and EXT2;
- and
- (c) comparing the expression level of at least one cancer gene marker to an expression level of a corresponding cancer gene marker in a sample of bodily fluids from a non-cancerous control, and thereby detecting the presence and/or severity of lung and/or colorectal cancer;
- wherein:
- (i) an increase in the expression level of DUSP6, GRB2, MCM4 and/or NF1 in the test sample as compared to the level of the corresponding marker in the control is an indication that the subject is at risk of developing lung cancer;
- (ii) an increase in the expression level of MDM2 in the test sample as compared to the level of the corresponding marker in the control is an indication that the subject is at risk of lung cancer recurrence;
- (iii) a decrease in the expression level of EIF2S3, MMD, and/or RNF4 in the test sample as compared to the level of the corresponding marker in the control is an indication that the subject is at risk of developing lung cancer;
- (iv) an increase in the expression level of DUSP6, GRB2, MDM2 and/or NF1 in the test sample as compared to the level of the corresponding marker in the control is an indication that the subject is at risk of developing colorectal cancer;
- and
- (v) a decrease in the expression level of EIF2S3, MMD, EXT2, and/or RNF4 in the test sample as compared to the level of the corresponding marker in the control is an indication that the subject is at risk of developing colorectal cancer.
Dependencies are inferred from the claim text.