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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 |
|
 -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 |
|
| |
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15,200 |
82%; 67% |
| |
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15,900 |
82%; 100% |
| |
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17,500 |
64%; 67% |
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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% |
| |
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4,400, 15,900, 18,900, 23,000, 30,100 |
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Validation biomarker panel 1e: |
82%; 95% |
| |
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3,100, 13,900, 21,000, 79,000, 106,700 |
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Validation biomarker panel 2f: |
73%; 95% |
| |
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5,100, 16,900, 28,000, 93,000 |
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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--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 |
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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. |
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a This table is reproduced from Ref. 46 with permission from the copyright owners.
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