Table 1.
Accuracy of classification of the nine NCI-60 panel cancer types using various profiling technologies*
Adjusted P value threshold for gene selection |
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Genes analyzed | Gene expression profiling assays | 0.25 | 0.1 | 0.05 | 0.02 | 0.01 | 0.005 | 0.001 |
380 MDR-linked genes | TLDA | 0.73 | 0.69 | 0.71 | 0.68 | 0.66 | 0.68 | 0.69 |
HG-U133A array | 0.71 | 0.64 | 0.66 | 0.66 | 0.61 | 0.59 | 0.61 | |
ABC transporter genes | TLDA | 0.59 | 0.61 | 0.53 | 0.42 | 0.46 | 0.44 | 0.29 |
HG-U133A array | 0.37 | 0.39 | 0.36 | 0.37 | 0.31 | 0.18† | 0‡ | |
SybrGreen-based qRT-PCR | 0.43 | 0.45 | 0.40 | 0.40 | 0.32 | 0.23 | 0.25 | |
Biomark 48.48 | 0.53 | 0.53 | 0.42 | 0.42 | 0.47 | 0.46 | 0.44 | |
SLC genes | HG-U133A array | 0.61 | 0.63 | 0.64 | 0.63 | 0.63 | 0.54 | 0.58 |
14,500 genes | HG-U133A array | 0.20 | 0.20 | 0.22 | 0.25 | 0.31 | 0.32 | 0.47 |
*Seventy-one percent of the cell lines were correctly classified at P = 0.05 and 69% at P = 0.001 with the TLDA 380 gene MDR set, whereas the expression profiles of the same genes obtained from HG-U133A oligonucleotide microarray analysis classified the 60 cancer cell lines with only 66% accuracy at P = 0.05 and 61% at P = 0.001. Confining the analysis to only ATP-Binding Cassette (ABC) transporter genes, some of the major mediators of multidrug resistance in cultured cells, generates less accurate classification. Only 53% of cell lines were correctly classified at P = 0.05 and 29% at P = 0.001, whereas microarray analysis of the same genes provides the worst results, with 36% accuracy at P = 0.05, with no classification achievable at P = 0.001. ABC transporter gene expression profiling using Sybr Green-based qRT-PCR provides intermediate results with 40% of cell lines properly classified at P = 0.05 and 25% at P = 0.001. Using Biomark 48.48, a high-throughput nanofluidic TaqMan-based qRT-PCR platform, the classification accuracy reaches 44% at P = 0.001. Solute carriers belong to a large family of uptake transporters that are also important MDR mediators. Their expression profiles measured by HG-U133A provide more accurate classification than the ABC transporter genes, with 64% at P = 0.05 and 58% at P = 0.001. Interestingly, the expression profiles of the 14,500 genes on the HG-U133A array do not improve the classification accuracy of the 9 cancer types, as only 22% of the cancer cell lines are correctly classified at P = 0.05, whereas an accuracy of 47% is achieved at P = 0.001. The reason for this apparent paradox is that at lower statistical significance (P < 0.05), more genes are being analyzed and the background noise is greater than at P < 0.001, which reduces the accuracy.
†Three samples unclassified.
‡Fifty-four samples unclassified.