Early detection of hepatocellular carcinoma in high risk populations using MALDI-TOF mass spectrometry
Hepatocellular carcinoma (HCC) is detected in a patient with liver disease. Mass spectrometry data from a blood-based sample from the patient is compared to a reference set of mass-spectrometry data from a multitude of other patients with liver disease, including patients with and without HCC, in a general purpose computer configured as a classifier. The classifier generates a class label, such as HCC or No HCC, for the test sample. A laboratory system for early detection of HCC in patients with liver disease is also disclosed. Alternative testing strategies using AFP measurement and a reference set for classification in the form of class-labeled mass spectral data from blood-based samples of lung cancer patients are also described, including multi-stage testing.
1. A method of detecting a class label in a liver disease patient comprising:
a) conducting mass spectrometry on a blood-based sample of the patient and obtaining mass spectrometry data;
(b) obtaining integrated intensity values in the mass spectral data of a multitude of pre-determined mass-spectral features; and
(c) operating on the mass spectral data with a programmed computer implementing a classifier;
wherein in the operating step the classifier compares the integrated intensity values with feature values of a training set of class-labeled mass spectral data obtained from a multitude of other patients with liver disease with the values obtained in step (b) with a classification algorithm and detects a class label for the sample.
2. The method of claim 1 , wherein the mass spectrometry comprises performing MALDI-TOF mass spectrometry by subjecting the blood-based sample to at least 100,000 laser shots and acquiring mass spectral data.
3. The method of claim 1 , wherein the classifier is obtained from filtered mini-classifiers combined using a regularized combination method.
4. The method of claim 3 , wherein the mini-classifiers perform classifications using single features, pairs of features, or single features, pairs of features and triplets of features in the feature values of a training set.
5. The method of claim 1 , wherein the obtaining step (b) comprises obtaining integrated intensity values of at least 50 features listed in one of the Appendices.
6. The method of claim 5 , wherein the obtaining step comprises obtaining integrated intensity values of at least 100 features listed in Example 1 Appendix A or Example 2 Appendix C.
7. The method of claim 5 , wherein the obtaining step comprises obtaining integrated intensity values of all the features of one of the Appendices.
8. The method of claim 1 , wherein the training set comprises all or a subset of a set of samples used to develop the classifier.
9. The method of claim 8 , wherein the training set is a subset of the set of samples used to develop the classifier pruned to remove those patients who have high AFP expression levels.
10. The method of claim 1 , wherein the feature values consist of the mass spectral features and AFP expression level.