Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse
Abstract
:1. Introduction
2. Results
2.1. CRC aCGH Profile
2.2. Expression Analysis of Candidate Oncogenes
3. Discussion
4. Materials and Methods
4.1. CRC Samples
4.2. Microsatellite Instability Analysis
4.3. Genomic Landscaping Using aCGH
4.4. Data Clustering and Statistical Analysis
4.5. Data Preprocessing of Affymetrix Microarray Gene Expression
4.6. Estimation of Epithelial-Mesenchymal Transition Score
4.7. Statistical Analysis
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
aCGH | Array comparative genomic hybridization |
CRC | Colorectal Cancer |
CAN | Copy number aberration |
OS | Overall survival |
DFS | Disease free survival |
EMT | Epithelial mesenchymal transition |
MSI | Microsatellite instable |
MSS | Microsatellite stable |
MMR | Mismatch repair |
STAC | Significance testing for aberrant copy number |
DLRS | Derivative of log ratio spread |
CNG | Copy number gain |
CNL | Copy number loss |
FFPE | Formalin-fixed paraffin embedded |
FASST2 | Fast Adaptive State Segmentation Technique |
SPPS | survival predictive power statistical |
BinReg | Binary regression |
SAM | Significance analysis of microarray |
ROC | Receiver-operating characteristics curve |
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Patients’ Characteristics | Stage II Who Stayed Disease Free | Stage II with Local Recurrences | Stage II Who Relapsed with Distant Metastasis | p Value a | |
---|---|---|---|---|---|
Mean age in years | 64.4 | 75.5 | 75.4 | 0.004 b | |
Sex | Male | 41 | 2 | 5 | 0.43 |
Female | 37 | 5 | 6 | ||
Total | 78 | 7 | 11 | ||
Site | Right | 19 | 2 | 1 | 0.16 |
Left | 28 | 1 | 9 | ||
Rectum | 16 | 1 | 1 | ||
Unknown | 15 | 3 | 0 | ||
T-stage | T3 | 44 | 3 | 9 | 0.27 |
T4 | 19 | 4 | 2 | ||
Unknown | 15 | 0 | 0 | ||
Differentiation | Well | 10 | 1 | 1 | 0.8 |
Moderate | 56 | 5 | 9 | ||
Poor | 5 | 1 | 0 | ||
Unknown | 7 | 0 | 1 | ||
MMR status | MSI | 14 | 1 | 0 | 0.45 |
MSS | 59 | 5 | 9 | ||
Unknown | 5 | 1 | 2 | ||
Follow-up | Mean DFS | 9.5 years | 3.9 years | 3.08 years |
Gene | Gene ID | aCGH CNA Event | %CNA Overlap with Normal | Cox’s OS (p-Value) | Cox’s DFS (p-Value) |
---|---|---|---|---|---|
ADRA1A | 148 | Loss | 0.42 | −0.40185, (0.152322) | −1.67582, (0.001948) |
ADRA1D | 146 | Loss | 1.15 | −0.5968, (0.020507) | 0.066504, (0.880385) |
ADRB3 | 155 | Loss | 0 | −1.21809, (0.002366) | −1.12818, (0.08601) |
APOBEC3D | 140564 | Loss | 0 | −0.45803, (0.24853) | −1.56085, (0.0224) |
BRF2 | 55290 | Loss | 0 | −0.45526, (0.02013) | 0.061887, (0.8515) |
C20orf202 | 400831 | Loss | 0.89 | −0.80141, (0.000481) | −0.19907, (0.628292) |
CABIN1 | 23523 | Loss | 4.02 | −0.47782, (0.0210) | −0.51601, (0.14935) |
CACNA1I | 8911 | Loss | 0 | −0.69524, (0.00404) | −0.73386, (0.082677) |
CSMD1 | 64478 | Loss | 0 | −0.01578, (0.956357) | −1.30789, (0.01948) |
DIO3 | 1735 | Loss | 1.76 | −0.32561, (0.041777) | −0.00829, (0.973719) |
EPHX2 | 2053 | Loss | 0.42 | 0.036582, (0.61411) | −0.30515, (0.0099) |
FAM83F | 113828 | Loss | 0 | −0.13746, (0.287004) | −0.72925, (0.00085) |
GP1BB | 2812 | Loss | 0 | −0.56827, (0.000246) | −0.19289, (0.495577) |
KIAA1656 | 85371 | Loss | 0 | −0.60241, (0.01922) | −1.02118, (0.032326) |
LOC339593 | 339593 | Loss | 0.17 | 0.29021, (0.385267) | −1.12678, (0.047789) |
MCM8 | 84515 | Loss | 0 | 0.043419, (0.614947) | −0.31948, (0.034203) |
NAT1 | 9 | Loss | 0 | 0.028159, (0.713606) | −0.36337, (0.007197) |
NAT2 | 10 | Loss | 0 | −0.09059, (0.160865) | −0.30169, (0.003804) |
HNF6 | 3175 | Loss | 0 | −0.66924, (0.017955) | −0.51152, (0.31) |
PCDHGA11 | 56105 | Loss | 0 | −0.85799, (0.001447) | −0.577, (0.33928) |
RAB11FIP1 | 80223 | Loss | 0 | −0.38036, (5.55× 10−05) | −0.02196, (0.87) |
SPAG11A | 653423 | Loss | 68.65 | −0.81665, (0.001447) | −0.13298, (0.57) |
SIRPD | 128646 | Loss | 0.89 | −0.89166, (0.014166) | −0.13392, (0.82) |
TEX43 | 389320 | Loss | 0 | −0.46611, (0.175471) | −0.19907, (0.01162) |
TOP1P2 | 7152 | Loss | 0 | −1.13965, (0.005692) | 0.599602, (0.32) |
WDR5 | 11091 | Loss | 0 | −0.0007, (0.995962) | −0.52505, (0.024307) |
ZNF366 | 167465 | Loss | 0.07 | −0.76274, (0.01779) | −0.93429, (0.09208) |
ZNF703 | 80139 | Loss | 0 | −0.32601, (0.000744) | −0.14954, (0.366064) |
ZNRF3 | 84133 | Loss | 0 | −0.03445, (0.605797) | −0.33884, (0.002065) |
ANXA2P2 | 304 | Gain | 0 | 0.478663, (0.003259) | 0.997702, (0.000504) |
CDC42BPA | 8476 | Gain | 0 | 0.032966, (0.690294) | 0.401718, (0.005473) |
DOK5 | 55816 | Gain | 0.57 | 0.105512, (0.1) | 0.577502, (0.002218) |
DUSP14 | 11072 | Gain | 0.70 | 0.207902, (0.047604) | 0.709569, (0.000159) |
GLIS3 | 169792 | Gain | 1.25 | 0.0916, (0.210004) | 0.397791, (0.000566) |
ING1 | 3621 | Gain | 0 | 0.461934, (0.020587) | 0.127394, (0.710857) |
MPDZ | 8777 | Gain | 0 | 0.079568, (0.406857) | 0.657405, (3.98 × 10−5) |
PITPNC1 | 26207 | Gain | 0 | 0.257758, (0.029048) | 0.418362, (0.026674) |
SCEL | 8796 | Gain | 0 | 0.081094, (0.202236) | 0.301113, (0.000357) |
SEMG1 | 6406 | Gain | 0 | 0.098826, (0.043099) | 0.153704, (0.061048) |
SMU1 | 55234 | Gain | 0.73 | 0.36857, (0.008896) | 0.016381, (0.942047) |
USP32 | 84669 | Gain | 0 | 0.162429, (0.221638) | 0.586012, (0.01236) |
VLDLR | 7436 | Gain | 0.14 | −0.00629, (0.92868) | 0.323607, (0.004972) |
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Al-Temaimi, R.A.; Tan, T.Z.; Marafie, M.J.; Thiery, J.P.; Quirke, P.; Al-Mulla, F. Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse. Int. J. Mol. Sci. 2016, 17, 598. https://doi.org/10.3390/ijms17050598
Al-Temaimi RA, Tan TZ, Marafie MJ, Thiery JP, Quirke P, Al-Mulla F. Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse. International Journal of Molecular Sciences. 2016; 17(5):598. https://doi.org/10.3390/ijms17050598
Chicago/Turabian StyleAl-Temaimi, Rabeah A., Tuan Zea Tan, Makia J. Marafie, Jean Paul Thiery, Philip Quirke, and Fahd Al-Mulla. 2016. "Identification of 42 Genes Linked to Stage II Colorectal Cancer Metastatic Relapse" International Journal of Molecular Sciences 17, no. 5: 598. https://doi.org/10.3390/ijms17050598