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Biology Articles » Methods & Techniques » Mass Spectrometry as a Diagnostic and a Cancer Biomarker Discovery Tool » Tables

Tables
- Mass Spectrometry as a Diagnostic and a Cancer Biomarker Discovery Tool

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TABLE I Some established cancer biomarkers

Biomarkera Cancer typeb

{alpha}-Fetoprotein (AFP) Hepatoma; testicular cancer
Carcinoembryonic antigen (CEA) Colon; breast; lung; pancreatic
PSA Prostate
CA125 Ovarian
CA15.3 Breast
CA19.9 Gastrointestinal
Immunoglobulins B cell dyscrasias
Chroriogonadotropin (hCG) Testicular cancer; trophoblastic tumors
Steroid hormone receptors Breast

a All of these markers are used as aids in diagnosis, prognosis, and monitoring of therapy; steroid hormone receptors are used for predicting therapeutic response to antiestrogens.

b All markers measured in serum except steroid hormone receptors, which are measured in cancer tissues.


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TABLE II Comparison of five reports for prostate cancer diagnosis based on SELDI-TOF technologya

Study Chip type Distinguishing peaks m/zb Diagnostic sensitivity and specificity

Petricoin et al. (39) Hydrophobic C16 2,092, 2,367, 2,582, 3,080, 4,819, 5,439, 18,220 95%; 78–83%
Adam et al. (40) IMAC-Cu 4,475, 5,074, 5,382, 7,024, 7,820, 8,141, 9,149, 9,507, 9,656 83%; 97%
Qu et al. (41) IMAC-Cu Non-cancer vs cancer: 3,963, 4,080, 6,542, 6,797, 6,949, 6,991, 7,024, 7,885, 8,067, 8,356, 9,656, 9,720 Healthy vs BPHc: 3,486, 4,071, 4,580, 5,298, 6,099, 7,054, 7,820, 7,844, 8,943 97–100%; 97–100%
Banez et al. (42) WCX2 3,972, 8,226, 13,952, 16,087, 25,167, 33,270 63%; 77%
  IMAC-Cu 3,960, 4,469, 9,713, 10,266, 22,832 66%; 38%
Lehrer et al. (43) Hydrophobic H4 Cancer and BPH vs controls: 100% (specificity)
    15,200, 15,900, 17,500  
        Cancer vs BPH  
        15,200 82%; 67%
        15,900 82%; 100%
        17,500 64%; 67%

a This table is modified and expanded from Refs. 46 and 68.

bm/z ratios were rounded to whole numbers for simplicity. m/z ratios in bold represent those identified by Adam et al. (40) and Qu et al. (41) for differentiating cancer from non-cancer patients. The underlined m/z ratio represents a peak identified by Adam et al. (40) for differentiating cancer from non-cancer patients and by Qu et al. (41) for differentiating healthy individuals from patients with benign prostatic hyperplasia.

c BPH, benign prostatic hyperplasia.

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TABLE III Comparison of two reports for ovarian cancer diagnosis based on SELDI-TOF technology

Study Chip type Distinguishing peaks, m/za Diagnostic sensitivity and specificityb

Petricoin et al. (30) C-16 534, 989, 2,111, 2,251, 2,465 100%; 95%
Kozak et al. (44) SAX2c Screening biomarker paneld: 96%; 83%
    4,400, 15,900, 18,900, 23,000, 30,100  
    Validation biomarker panel 1e: 82%; 95%
    3,100, 13,900, 21,000, 79,000, 106,700  
    Validation biomarker panel 2f: 73%; 95%
    5,100, 16,900, 28,000, 93,000  

am/z ratios were rounded to whole numbers for simplicity.

b Somewhat different values were obtained for different sets of samples; see original papers for more details.

c Strong anion-exchange chip.

d Differentiates healthy from neoplastic (benign and malignant) disease. In this paper, the molecular masses of the markers are given instead of m/z ratios. All values were reported with one decimal point accuracy.

e Differentiates healthy and benign disease from malignant disease.

f In Ref. 30, there is a limit to the molecular mass or m/z ratio monitored (up to 20,000).


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TABLE IV Concentration of some abundant proteins, putative new cancer biomarkers identified by SELDI-TOF, and classical cancer biomarkers in seruma

Compound Approximate concentration Biomarker for cancer type Reference

  [pmol/liter]    
    Albumin 600,000,000 38
    Immunoglobulins 30,000,000 38
    C-reactive protein 40,000 38
SELDI-TOF proteinsb      
    Apolipoprotein A1 40,000,000 Ovarian 49
    Transthyretin (prealbumin) fragment 6,000,000 Ovarian 49
    Inter-{alpha}-trypsin inhibitor fragment 4,000,000 Ovarian 49
    Haptoglobin-a-subunit 1,000,000 Ovarian 50
    Vitamin D-binding protein 10,000,000 Prostate 51
    Serum amyloid A protein 20,000,000 Nasopharyngeal 52
Classical tumor markers      
    Alpha-fetoprotein 150 Hepatoma, testicular 38
    PSA 140 Prostate 38
    Carcinoembryonic antigen 30 Colon, lung, breast, pancreatic 38
    Human choriogonadotropin 20 Testicular, choriocarcinoma 38
    Human choriogonadotropin-ß subunit 2 Testicular, choriocarcinoma 38

a This table is modified and expanded from Ref. 68.

b Apolipoprotein A1 is produced in liver and intestine; all other proteins are mainly produced in the liver (38).

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TABLE V Some open questions related to diagnostic SELDI-TOF technologya

1. Identity and serum concentration of discriminating molecules not known. Mass spectrometry is a largely qualitative technique. Relationship between peak height and molecule abundance is not linear and could be very complex.
2. Discriminating peaks identified by different investigators for the same disease are different.
3. Data not easily reproducible between laboratories, making validation difficult.
4. Optimal sample preparation for the same disease differs between investigators. Sample handling and preparation may be a critical issue.
5. Validated serum cancer markers (e.g. PSA, CA125, etc.) that could serve as positive controls are not identified by this technology.
6. Nonspecific absorbtion matrices favor extraction of high-abundance proteins/peptides at the expense of low-abundance proteins/peptides. Unknown recovery of "informative" molecules versus "uninformative" molecules. Analytical sensitivity of mass spectrometry in the context of these experiments is not known.
7. Technique likely measures peptides or other molecules present in high abundance in serum (e.g. mg/liter to g/liter range). Such molecules are unlikely to originate from cancer tissue. More likely, they represent cancer epiphenomena.
8. No known relationship between discriminatory molecules and cancer biology.

a This table is reproduced from Ref. 46 with permission from the copyright owners.


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