Modified eQTL and Somatic DNA Segment Alterations in Esophageal Squamous Cell Carcinoma for Genes Related to Immunity, DNA Repair, and Inflammation
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Patient Information
3.2. Pathway-Based Analyses
3.3. Two eQTL Analyses of Gene Expression and SNP Genotype
3.3.1. Classical eQTL Analysis (in Normal Esophagus Tissue Only)
3.3.2. Modified eQTL Analysis (Fold Change Based on Tumor vs. Normal Tissue)
3.3.3. Shared Significant eQTLs in the Classical and Modified Approaches
3.4. Somatic DNA Segment Alterations (Copy Number (CN) Alterations, Allele Imbalance (AI) and LOH) in Genes Shared by the Significant eQTLs from the Two Approaches
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Appendix A.1. Biological Specimen Collection and Processing
Appendix A.1.1. U133A Arrays (U133A, U133A v.2.0, and U133 Plus2) and Data Normalization
Appendix A.1.2. GeneChip Human Mapping Arrays (500K, SNP 5.0, and SNP 6.0)
Appendix A.1.3. GeneChip Data Analysis (500K, SNP 5.0, and SNP 6.0 Arrays)
Appendix A.2. Pathway Resources
Appendix A.3. Association and eQTL Analyses
References
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(a) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Gene No | Gene Name | Chr | SNP | Probeset | Classical eQTL | p Value | Modified eQTL | p Value | SNP | |
rho | rho | No | ||||||||
1 | CD46 | 1q32 | rs7144 | 208783_s_at | 0.310 | 0.002 | −0.273 | 0.006 | 1 | |
rs2724391 | 208783_s_at | 0.261 | 0.010 | −0.211 | 0.037 | 2 | ||||
2 | CD58 | 1p13 | rs1335532 | 216942_s_at | 0.226 | 0.024 | −0.210 | 0.036 | 3 | |
3 | COL11A1 | 1p21 | rs2061705 | 37892_at | −0.223 | 0.028 | 0.242 | 0.017 | 4 | |
4 | CYP2C18 | 10q24 | rs1409654 | 215103_at | −0.321 | 0.001 | 0.245 | 0.014 | 5 | |
rs2296679 | 215103_at | −0.312 | 0.002 | 0.240 | 0.016 | 6 | ||||
rs1409654 | 208126_s_at | −0.281 | 0.005 | 0.221 | 0.028 | 7 | ||||
5 | CYP2C9 | 10q24 | rs4086116 | 214420_s_at | −0.206 | 0.040 | 0.209 | 0.037 | 8 | |
rs4917639 | 214420_s_at | −0.206 | 0.040 | 0.209 | 0.037 | 9 | ||||
6 | DAPK1 | 9q21.33 | rs1964911 | 211214_s_at | −0.294 | 0.003 | 0.218 | 0.029 | 10 | |
7 | GLS2 | 12q13 | rs6581096 | 205531_s_at | −0.201 | 0.044 | 0.226 | 0.024 | 11 | |
8 | N4BP2L1 | 13q12-q13 | rs1207952 | 211390_at | 0.224 | 0.025 | −0.301 | 0.002 | 12 | |
9 | NCAM1 | 11q23.1 | rs2850303 | 212843_at | 0.271 | 0.006 | −0.355 | 0.000 | 13 | |
rs584427 | 212843_at | 0.251 | 0.013 | −0.314 | 0.002 | 14 | ||||
rs1821693 | 212843_at | 0.242 | 0.016 | −0.352 | 0.000 | 15 | ||||
10 | NCAPD2 | 12p13.3 | rs917634 | 201774_s_at | −0.337 | 0.001 | 0.198 | 0.048 | 16 | |
11 | PARD3 | 10p11.22- | rs2496720 | 221280_s_at | −0.262 | 0.009 | 0.247 | 0.014 | 17 | |
p11.21 | rs2496720 | 210094_s_at | −0.215 | 0.033 | 0.231 | 0.022 | 18 | |||
12 | PDCD1LG2 | 9p24.2 | rs1360238 | 220049_s_at | −0.202 | 0.044 | 0.295 | 0.003 | 19 | |
13 | PTPRM | 18p11.2 | rs12606738 | 216292_at | −0.202 | 0.046 | 0.222 | 0.028 | 20 | |
14 | TCF7L1 | 2p11.2 | rs12714137 | 221016_s_at | −0.211 | 0.037 | 0.213 | 0.035 | 21 | |
15 | TCF7L2 | 10q25.3 | rs1028629 | 212761_at | −0.299 | 0.003 | 0.205 | 0.041 | 22 | |
16 | ZBTB16 | 11q23.1 | rs2852796 | 205883_at | −0.237 | 0.017 | 0.243 | 0.015 | 23 | |
17 | MS4A1 | 11q12 | rs4939363 | 210356_x_at | 0.216 | 0.033 | −0.224 | 0.027 | 24 | |
rs4939362 | 210356_x_at | 0.199 | 0.047 | −0.202 | 0.044 | 25 | ||||
rs1941030 | 210356_x_at | 0.199 | 0.047 | −0.202 | 0.044 | 26 | ||||
18 | ST6GAL1 | 3q27-q28 | rs12495026 | 214971_s_at | −0.242 | 0.016 | 0.220 | 0.028 | 27 | |
rs12495023 | 214971_s_at | −0.236 | 0.018 | 0.213 | 0.035 | 28 | ||||
(b) | ||||||||||
Gene No | Gene | Cytoband | Classical eQTL SNP | Probeset | rho | pValue | Modified eQTL SNP | Probeset | rho | pValue |
1 | CACNA1C | 12p13.3 | rs2239097 | 208020_s_at | 0.229 | 0.0222 | rs2239097 | 211592_s_at | −0.208 | 0.037 |
rs2283318 | 208020_s_at | 0.219 | 0.0297 | |||||||
2 | CACNB2 | 10p12 | rs1034139 | 215365_at | −0.202 | 0.0434 | rs4748472 | 207776_s_at | −0.245 | 0.015 |
3 | IGF1R | 15q26.3 | rs2684811 | 203627_at | −0.352 | 0.0003 | rs12908437 | 208441_at | 0.218 | 0.029 |
4 | ITPR1 | 3p26-p25 | rs11714599 | 216944_s_at | 0.204 | 0.0431 | rs3805032 | 203710_at | −0.253 | 0.012 |
rs11714599 | 203710_at | 0.204 | 0.0433 | rs3805032 | 203710_at | −0.253 | 0.012 | |||
rs304051 | 216944_s_at | 0.250 | 0.012 | |||||||
rs304053 | 216944_s_at | 0.250 | 0.012 | |||||||
rs304051 | 222314_x_at | −0.218 | 0.029 | |||||||
5 | rs304053 | 222314_x_at | −0.218 | 0.029 | ||||||
NRP1 | 10p12 | rs4934583 | 210615_at | −0.213 | 0.0335 | rs869636 | 210510_s_at | −0.309 | 0.002 | |
rs2776928 | 210510_s_at | −0.231 | 0.022 | |||||||
rs2776928 | 212298_at | −0.215 | 0.032 | |||||||
6 | RARB | 3p24 | rs922939 | 208412_s_at | 0.227 | 0.0238 | rs12630664 | 208413_at | −0.293 | 0.003 |
rs17016781 | 208413_at | −0.220 | 0.0282 | rs12631063 | 208413_at | −0.271 | 0.007 | |||
rs3773439 | 208412_s_at | 0.271 | 0.007 | |||||||
rs1730223 | 208412_s_at | 0.269 | 0.007 | |||||||
rs17016773 | 208412_s_at | 0.266 | 0.008 | |||||||
rs11707637 | 208412_s_at | 0.265 | 0.008 | |||||||
rs7610831 | 208412_s_at | 0.253 | 0.011 | |||||||
rs17029657 | 208412_s_at | 0.239 | 0.017 | |||||||
rs6800566 | 217020_at | 0.225 | 0.024 | |||||||
rs17016738 | 208412_s_at | 0.216 | 0.031 |
No | Gene | Cytoband | Gene Expression: Frequency | Somatic DNA Segment Alterations: Frequency | |||||
---|---|---|---|---|---|---|---|---|---|
Over | Under | Abnormal | AI Only | CN Gain with/without AI | CN Loss or LOH with/without AI | Total with Alterations | |||
1 | CACNA1C | 12p13.3 | 0.06 | 0.16 | 0.22 | 0.13 | 0.21 | 0.05 | 0.39 |
2 | CACNB2 | 10p12 | 0.09 | 0.36 | 0.45 | 0.22 | 0.05 | 0.16 | 0.43 |
3 | CD46 | 1q32 | 0.14 | 0.25 | 0.39 | 0.24 | 0.20 | 0.00 | 0.43 |
4 | CD58 | 1p13 | 0.33 | 0.13 | 0.46 | 0.17 | 0.03 | 0.09 | 0.29 |
5 | COL11A1 | 1p21 | 0.95 | 0 | 0.95 | 0.16 | 0.03 | 0.12 | 0.3 |
6 | CYP2C18 | 10q24 | 0.07 | 0.81 | 0.88 | 0.24 | 0.00 | 0.11 | 0.34 |
7 | CYP2C9 | 10q24 | 0.04 | 0.62 | 0.64 | 0.24 | 0.00 | 0.11 | 0.34 |
8 | DAPK1 | 9q34.1 | 0.21 | 0.22 | 0.43 | 0.33 | 0.12 | 0.24 | 0.68 |
9 | GLS2 | 12q13 | 0.28 | 0.18 | 0.46 | 0.16 | 0.08 | 0.03 | 0.26 |
10 | IGF1R | 15q26.3 | 0.54 | 0.03 | 0.57 | 0.17 | 0.18 | 0.08 | 0.43 |
11 | ITPR1 | 3p26-p25 | 0.09 | 0.47 | 0.56 | 0.24 | 0.03 | 0.38 | 0.64 |
12 | MS4A1 | 11q12 | 0.32 | 0.2 | 0.52 | 0.26 | 0.03 | 0.05 | 0.34 |
13 | N4BP2L1 | 13.q13.1 | 0.13 | 0.17 | 0.3 | 0.29 | 0.03 | 0.28 | 0.59 |
14 | NCAM1 | 11q23.1 | 0.09 | 0.27 | 0.36 | 0.26 | 0.04 | 0.18 | 0.49 |
15 | NCAPD2 | 12p13.3 | 0.81 | 0.05 | 0.86 | 0.18 | 0.14 | 0.03 | 0.36 |
16 | NRP1 | 10p12 | 0.52 | 0.08 | 0.6 | 0.22 | 0.07 | 0.09 | 0.38 |
17 | PARD3 | 10p11 | 0.03 | 0.47 | 0.5 | 0.17 | 0.07 | 0.16 | 0.39 |
18 | PDCD1LG2 | 9p24.2 | 0.13 | 0.08 | 0.21 | 0.43 | 0.05 | 0.29 | 0.78 |
19 | PTPRM | 18p11.2 | 0.26 | 0.09 | 0.35 | 0.17 | 0.16 | 0.08 | 0.41 |
20 | RARB | 3p24 | 0.04 | 0.15 | 0.19 | 0.30 | 0.00 | 0.36 | 0.66 |
21 | ST6GAL1 | 3q27-q28 | 0.33 | 0.07 | 0.4 | 0.04 | 0.68 | 0.01 | 0.74 |
22 | TCF7L1 | 2p11.2 | 0.32 | 0.27 | 0.59 | 0.16 | 0.13 | 0.03 | 0.32 |
23 | TCF7L2 | 10q25.3 | 0.17 | 0.13 | 0.3 | 0.24 | 0.03 | 0.14 | 0.41 |
24 | ZBTB16 | 11q23.1 | 0.05 | 0.74 | 0.79 | 0.22 | 0.03 | 0.21 | 0.46 |
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Yang, H.H.; Liu, H.; Hu, N.; Su, H.; Wang, C.; Giffen, C.; Goldstein, A.M.; Taylor, P.R.; Lee, M.P. Modified eQTL and Somatic DNA Segment Alterations in Esophageal Squamous Cell Carcinoma for Genes Related to Immunity, DNA Repair, and Inflammation. Cancers 2022, 14, 1629. https://doi.org/10.3390/cancers14071629
Yang HH, Liu H, Hu N, Su H, Wang C, Giffen C, Goldstein AM, Taylor PR, Lee MP. Modified eQTL and Somatic DNA Segment Alterations in Esophageal Squamous Cell Carcinoma for Genes Related to Immunity, DNA Repair, and Inflammation. Cancers. 2022; 14(7):1629. https://doi.org/10.3390/cancers14071629
Chicago/Turabian StyleYang, Howard H., Huaitian Liu, Nan Hu, Hua Su, Chaoyu Wang, Carol Giffen, Alisa M. Goldstein, Philip R. Taylor, and Maxwell P. Lee. 2022. "Modified eQTL and Somatic DNA Segment Alterations in Esophageal Squamous Cell Carcinoma for Genes Related to Immunity, DNA Repair, and Inflammation" Cancers 14, no. 7: 1629. https://doi.org/10.3390/cancers14071629