Metabolomic Signatures for Predicting, Diagnosing, and Prognosing Various Diseases Including Cancer

Abstract

A system and method for using new biomarkers to assess individual diseases is provided. In one embodiment of the present invention, absolute quantification of annotated metabolites by mass spectrometry is used to identify certain biomarkers and derivatives thereof (i.e., signatures), which are then used to screen for, diagnose, predict, prognose, and treat various diseases, including, but not limited to, breast cancer, ovarian cancer, colorectal cancer, pancreatic cancer, and acute graft-versus-host disease.

What is claimed is: 
     
         1 . A method for assessing a human patient for colon cancer, comprising:
 using a technology selected from chromatography, spectroscopy, and spectrometry to quantify a plurality of metabolites included in a blood sample obtained from said human patient, including at least Hexadecenoylcarnitine and Phosphatidylcholine;   normalizing at least said Hexadecenoylcarnitine and said Phosphatidylcholine as quantified using said technology;   comparing at least a result of an equation comprising at least a first ratio of said Hexadecenoylcarnitine and said Phosphatidylcholine, as normalized, to at least one predetermined value to both diagnose said human patient for said colon cancer and determine a prognosis for said human patient;   wherein said diagnosis includes at least whether said human patient has colon cancer and said prognosis includes at least a risk factor associated with said colon cancer.   
     
     
         2 . The method of  claim 1 , wherein said step of quantifying and normalizing said Phosphatidylcholine further comprises the step of quantifying and normalizing Phosphatidylcholine with diacyl residue sum C34:2. 
     
     
         3 . The method of  claim 2 , wherein said first ratio further comprises said Hexadecenoylcarnitine and said Phosphatidylcholine with diacyl residue sum C34:2. 
     
     
         4 . The method of  claim 1 , wherein said first ratio is said Hexadecenoylcarnitine to said Phosphatidylcholine. 
     
     
         5 . The method of  claim 1 , further comprising the steps of quantifying and normalizing Glutaconylcarnitine, where a denominator of said first ratio is said Phosphatidylcholine to Glutaconylcarnitine, as normalized. 
     
     
         6 . The method of  claim 3 , further comprising the steps of quantifying and normalizing Glutaconylcarnitine, where a denominator of said first ratio is said Phosphatidylcholine with diacyl residue sum C34:2 to Glutaconylcarnitine, as normalized. 
     
     
         7 . The method of  claim 1 , further comprising the steps of quantifying and normalizing at least one of Sphingomyelin and Hydroxysphingomyelin, where a numerator of said first ratio is said one of said Sphingomyelin and Hydroxysphingomyelin to Hexadecenoylcarnitine, as normalized. 
     
     
         8 . The method of  claim 1 , further comprising the steps of quantifying and normalizing at least one of Sphingomyelin with acyl residue sum C20:1, Glutaconylcarnitine, Hydroxysphingomyelin with acyl residue sum C14:1, and Hydroxysphingomyelin with acyl residue sum 16:1, where a numerator of said first ratio is said one of said Sphingomyelin with acyl residue sum C20:1, Glutaconylcarnitine, Hydroxysphingomyelin with acyl residue sum C14:1, and Hydroxysphingomyelin with acyl residue sum 16:1 to Hexadecenoylcarnitine, as normalized. 
     
     
         9 . The method of  claim 1 , wherein said step of normalizing at least said Hexadecenoylcarnitine and said Phosphatidylcholine further comprises using at least a log-transformation to normalize at least said Hexadecenoylcarnitine and said Phosphatidylcholine. 
     
     
         10 . The method of  claim 1 , wherein said risk factor comprises at least a survival rate of said human patient from said colon cancer. 
     
     
         11 . The method of  claim 1 , wherein said risk factor comprises at least a relapse rate of said colon cancer. 
     
     
         12 . The method of  claim 1 , wherein said step of comparing is further used to determine a degree of said colon cancer, said determined degree being one of non-invasive, invasive, metastatic, and lethal. 
     
     
         13 . The method of  claim 1 , wherein said step of comparing is further used to determine a viability of at least one treatment for said colon cancer. 
     
     
         14 . A system for assessing a human patient for colon cancer, comprising:
 a computing system comprising at least one memory device for storing machine readable instructions adapted to perform the steps of:
 receive a plurality of quantified metabolites from a sample provided by said human patient, including at least Hexadecenoylcarnitine and Phosphatidylcholine; 
 normalize said plurality of quantified metabolites; 
 compare at least a result of an equation comprising at least a first ratio of said Hexadecenoylcarnitine and said Phosphatidylcholine, as normalized, to at least one predetermined value to determine at least one level of similarity therebetween; and 
 use said at least one level of similarity to determine a diagnosis and a prognosis for said human patient regarding said colon cancer; 
   wherein said diagnosis includes at least whether said human patient has colon cancer and said prognosis includes at least a risk factor associated with said colon cancer.   
     
     
         15 . The system of  claim 14 , wherein said Hexadecenoylcarnitine is said numerator and said Phosphatidylcholine is said denominator in said first ratio. 
     
     
         16 . The system of  claim 14 , wherein said Phosphatidylcholine comprises Phosphatidylcholine with diacyl residue sum C34:2. 
     
     
         17 . The system of  claim 16 , wherein said Hexadecenoylcarnitine is said numerator and said Phosphatidylcholine with diacyl residue sum C34:2 is said denominator in said first ratio. 
     
     
         18 . The system of  claim 14 , wherein said quantified metabolites further include Glutaconylcarnitine, where a denominator of said first ratio is said Phosphatidylcholine to said Glutaconylcarnitine, as normalized. 
     
     
         19 . The system of  claim 14 , wherein said quantified metabolites further include at least one of Sphingomyelin and Hydroxysphingomyelin, wherein said numerator of said first ratio is said at least one of said Sphingomyelin and said Hydroxysphingomyelin to said Hexadecenoylcarnitine, as normalized. 
     
     
         20 . The system of  claim 19 , wherein said quantified metabolites further include Glutaconylcarnitine, where a denominator of said first ratio is said Phosphatidylcholine to said Glutaconylcarnitine, as normalized.