Article Figures & Data
Figures
- Fig. 1.
Nine anticancer drugs and respective sensitivities in each of the 85 xenografts, evaluated by T/C. Red, high sensitivity to the drug; green, resistance; gray, combinations that were not tested.
- Fig. 2.
Two-dimensional hierarchical cluster analysis of expression profiles among 85 xenografts. In a, of 20,340 genes in the microarray, 961 were selected for this analysis by the criteria described in “Materials and Methods.” Red, genes that were overexpressed in tumors compared with a mixture of mRNAs from normal organs (brain, lung, liver, and kidney); green, downexpression; black, unchanged expression; and gray, no or weak expression. In b, in the sample axis, xenografts from NSCLC are indicated in red, those from small cell lung cancer in dark blue, those from pancreas in yellow, those from colon in green, those from brain (glioma) in lavender, those from neuroblastoma in pink, those from gastric cancer in gray (including a choriocarcinoma of the stomach, SC16), those from breast in orange (including two cystosarcoma phyllodes, MC3 and MC10, and one stromal sarcoma, MC6), those from ovary in purple, and those from choriocarcinoma in light blue. Data from MC9, a breast cancer xenograft that was analyzed independently, were clustered in the same terminal branch.
- Fig. 3.
Relationship between expression levels of GPX2 and MAP2K3 and sensitivity of tumors to CPM and VCR, respectively. In a, expression levels of GPX2 (log2 Cy5:Cy3) in all 85 xenografts are plotted in the Y axis, and their sensitivities to CPM (100-T/C) are plotted in the X axis. A correlation coefficient of r = −0.59 indicates negative correlation (P < 0.001). b, expression levels of GPX2 in the 11 xenografts derived from NSCLCs, showing a more significant negative association with sensitivity to CPM (r = −0.94, P < 0.001). c, expression levels of MAP2K3 in all 85 xenografts and negative association with sensitivity to VCR (r = −0.29, P < 0.05). d, expression levels of MAP2K3 in the 14 xenografts derived from breast cancers and more significant negative association with sensitivity to VCR (r = −0.91, P < 0.001).
- Fig. 4.
Panel of 333 genes commonly correlated with sensitivity or resistance to two or more anticancer drugs, not including 5FU and MTX. The number of genes and drugs that commonly correlate with each other are indicated. Green, a positive correlation (sensitive) between drug sensitivity and expression level of the gene; red, a negative correlation (resistance). Gradation of color patterns corresponded to the degree of correlation coefficient.
- Fig. 5.
Differences in the relationship between expression levels of TNFRSF14 and sensitivities to ACNU in all versus tissue-specific xenografts. In a, in all 85 xenografts, the correlation coefficient between expression level of TNFRSF14 and sensitivity of the tumor cells to ACNU (100-T/C) was weak (r = −0.42, P < 0.001). In b, in nine xenografts derived from NSCLCs, excluding two samples whose values for this gene were below cutoff, the correlation between expression level of TNFRSF14 and sensitivity to ACNU (100-T/C) was strong (r = −0.87, P < 0.001). In c and d, in nine xenografts from breast cancers and 13 from gastric cancers, the correlation between expression level of TNFRSF14 and sensitivity to ACNU was far weaker than that obtained in xenografts from NSCLCs (breast cancer: r = 0.14, P > 0.1; gastric cancer: r = −0.15, P > 0.1).
- Fig. 6.
Drug sensitivity scores for human cancer xenografts to each of five anticancer drugs are shown. The xenografts which were more sensitive to each drug are provided higher scores, and those that were resistant reveal lower scores. In a—e, correlation coefficients between the scores and the sensitivities of 85 xenografts to each drug are as follows: CPM, 0.72 (P = 8.8 × 10−15); ACNU, 0.69 (P = 3.0 × 10−13); ADR, 0.76 (P = 8.7 × 10−17); DDP, 0.67 (P = 4.6 × 10−12); and VCR, 0.69 (P = 8.0 × 10−13). Each point of xenograft sample indicates as follows: •, glioma; ○, breast cancer; ▴, choriocarcinoma; ▵, colon cancer; crosses, gastric cancer; ▪, lung cancer; □, neuroblastoma; ♦, ovarian cancer; and ⋄, pancreatic cancer.
Tables
- Table 1
Numbers of genes showing significant correlation with sensitivity to nine anticancer drugsa
All xenografts (85) NSCLC (11) Breast cancer (14) Gastric cancer (13) 5FU 240 184 69 72 ACNU 290 151 78 101 ADR 283 72 94 93 CPM 459 168 103 92 DDP 217 166 76 100 MMC 321 137 199 102 MTX 219 92 75 171 VCR 244 200 107 112 VLB 210 201 109 60 -
a These genes were identified not only in 85 xenografts but also in xenografts from NSCLC, breast cancer, and gastric cancer in order to explore the genes related to tissue-dependent chemosensitivity. These genes satisfied the following criteria: P < 0.01, and the absolute value of the slope of the regression line was larger than 1.5 between the 100-T/C range (see “Materials and Methods”).
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Volume 62, Issue 2
