Method for crystallizing low mass ions for diagnosing colorectal cancer and method for diagnosing colorectal cancer using same

Patent metadata

Field	Value
Publication number	US-9640375-B2
Application number	US-201113816560-A
Country	US
Kind code	B2
Filing date	Aug 12, 2011
Priority date	Aug 12, 2010
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

The present invention provides a method for determining low mass ions for diagnosing colorectal cancer by using a MALDI-TOF mass spectrometer to biostatistically analyze low mass ions, which are extracted from a biological sample, and a method for providing information for diagnosing colorectal cancer using same. The present inventions can provide a diagnostic method, which requires low cost and a short time for analysis, can analyze large areas, and which can provide superior and credible discriminations.

First claim

The invention claimed is:

1. A method for determining low mass ions for diagnosing colorectal cancer (CRC) in a mammal, the method comprising steps of:
(a) taking low mass ion mass spectra from a plurality of biological samples of a plurality of mammals wherein the biological samples being prepared by a chemical extracting step, using a mass spectrometer and extracting peak intensities of low mass ions from the low mass ion mass spectra;
(b) performing a biostatistical analysis on the acquired peak intensities to calculate a discriminant score (DS) for each peak;
(c) primarily selecting peaks of the respective cases from among the peaks, in which the primarily selected peaks meet a condition that an absolute value of a product of the peak intensities multiplied by factor loadings of the respective peaks exceeds T 1 ;
(d) secondarily selecting peaks from the primarily selected peaks for the respective cases, in which the secondarily selected peaks are commonly present in the cases which are T 2 or greater percent of the training set cases; and
(e) determining a group of low mass ions for diagnosing CRC with the peaks selected at the step (d)
wherein
after the step (d), the discriminant score (DS) is calculated only with the peaks selected at the step (d) so that sensitivity and specificity are calculated according to the calculated DS, and if the calculated sensitivity is less than N 3 or if the calculated specificity is less than N 4 , the T 1 and T 2 are changed so that the steps (c) and (d).

2. The method as set forth in claim 1 , wherein the step (d) comprises a step (d1) of primarily selecting peaks of the respective cases from among the peaks, in which the primarily selected peaks meet a condition that an absolute value of a product of the peak intensities multiplied by factor loadings of the respective peaks exceeds T 1 .

3. The method as set forth in claim 1 , wherein the step (d) further comprises a step (d1) of selecting predetermined peaks from among the peaks selected at the step (d) to calculate DS for validation set cases, calculating sensitivity and specificity according to the calculated DS, and if the calculated sensitivity is less than N 5 or if the calculated specificity is less than N 6 , re-selecting new peaks that are different from the predetermined peaks and reiterating a process of improving discrimination performance with respect to validation set cases and finally selecting mass value of the low mass ions for diagnosing CRC.

4. The method as set forth in claim 3 , wherein the low mass ions for diagnosing CRC comprise low mass ions of fibrinogen or fibrinogen alpha chain.

5. The method as set forth in claim 3 , wherein the low mass ions for diagnosing CRC comprises low mass ions of phosphoenolpyruvate (PEP).

6. The method as set forth in claim 1 , wherein the step (c) comprises:
a step (c1) of calculating sensitivity and specificity according to the calculated DS;
a step (c2) of excluding false positive or false negative cases from the plurality of cases, if the sensitivity is less than N 1 or if the specificity is less than N 2 , and reiterating the steps (a) to (b); and
a step (c3) of selecting the cases as the predetermined training set cases if the sensitivity is equal to or greater than N 1 and if the specificity is equal to or greater than N 2 .

7. The method as set forth in claim 1 , wherein the step (a) comprises a step (a1) of aligning low mass ion mass spectra acquired from the biological samples of the plurality of cases and importing.

8. The method as set forth in claim 1 , wherein the step (b) comprises:
a step (b1) of normalizing the imported peak intensities;
a step (b2) of scaling the normalized peak intensities; and
a step (b3) of calculating the DS by performing a biostatistical analysis on the scaled peak intensities.

9. The method as set forth in claim 8 , wherein the scaling is a Pareto scaling.

10. The method as set forth in claim 8 , wherein the biostatsitical analysis is a principal component analysis-based linear discriminant analysis (PCA-DA).

11. The method of claim 1 , wherein the peak intensities of low mass ions are extracted and the biostatistical analysis is performed with software in a computer.

Assignees

• Yoo Byong Chul
• Kim In Hoo
• Kim Kyung Hee
• Lee Jun Hwa
• Kim Kwang Gi
• Chang Hee Jin
• Kim Dae Yong
• Oh Jae Hwan
• Kim Byung Chang
• Park Ji Won
• Kim Sun Young
• Nat Cancer Ct

Inventors

• Yoo Byong Chul
• Kim In Hoo
• Kim Kyung Hee
• Lee Jun Hwa
• Kim Kwang Gi
• Chang Hee Jin
• Kim Dae Yong
• Oh Jae Hwan
• Kim Byung Chang
• Park Ji Won
• Kim Sun Young

Classifications

• G01N33/57535

  of the large intestine, e.g. colon, rectum or anus · CPC title

• G06F19/24

  Physics · mapped topic

• G06F19/703

  Physics · mapped topic

• G01N33/57419

  Physics · mapped topic

• G01N33/6848

  Methods of protein analysis involving mass spectrometry · CPC title