The Construction of a Multi-Gene Risk Model for Colon Cancer Prognosis and Drug Treatments Prediction
Abstract
:1. Introduction
2. Results
2.1. DEGs Identification
2.2. Gene Set Enrichment Analysis
2.3. Survival Curves of 47 Hub Genes and Their Expression Levels in COAD
2.4. PPI Network Construction
2.5. LASSO Regression Analysis
2.6. Immune Cell Infiltration Analysis
2.7. Mutation Analysis
2.8. Connectivity Map (cMAP) Analysis
2.9. Ferroptosis Analysis
3. Discussion
4. Materials and Methods
4.1. Data Collection
4.2. Performing Differential Gene Expression Analysis Using the Three Major R Packages, DESeq2, edgeR, and Limma
4.3. Functional Enrichment Analysis
4.4. Survival Analysis
4.5. PPI Network Construction
4.6. LASSO Regression Analysis
4.7. Immune Cell Infiltration Analysis
4.8. Mutation Analysis
4.9. Connectivity Map (cMAP) Analysis
4.10. Ferroptosis Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | Patients | Percentages (%) | |
---|---|---|---|
gender | male | 298 | 52.19 |
female | 271 | 47.46 | |
A/D | Alive | 442 | 77.41 |
Dead | 127 | 22.24 | |
Age, years | ≦69 | 272 | 47.80 |
>69 | 297 | 52.20 | |
T stage | T1 | 11 | 1.93 |
T2 | 95 | 16.64 | |
T3 | 390 | 68.30 | |
T4 | 39 | 6.83 | |
N stage | N0 | 335 | 58.67 |
N1 | 129 | 22.59 | |
N2 | 105 | 18.39 | |
M stage | M0 | 416 | 72.85 |
M1 | 81 | 14.19 | |
MX | 64 | 11.21 |
Name | Count | % | p-Value | Genes | |
---|---|---|---|---|---|
GO-BP | production of molecular mediator of immune response | 62 | 5.09 | 9.13 × 10−13 | CD22, PGC, SLC7A5, AICDA, CD160, CCR2, TREM1, VPREB3, CD36, APOA2, SLAMF9, TLR3, KLK7, MZB1, KIR2DL4, ELANE, IGKV4-1, IGKV6-21, IGKV3D-20, IGKV3D-11, IGKV1D-42, IGLV4-69, IGLV8-61, IGLV4-60, IGLV10-54, IGLV1-50, IGLV5-48, IGLV7-46, IGLV5-45, IGLV1-44, IGLV7-43, IGLV2-33, IGLV2-14, IGLV3-10, IGLV3-9, IGLV4-3, TRDV1, IGKV3D-15, IGKV6D-21, IGKV2D-30, IGKV1-6, IGKV3-20, IGKV1D-33, IGKV1-17, IGKV1-8, IGKV1-16, MIF, IGKV2-24, IGKV2D-24, IGKV1-9, IGKV1-39, IGKV2D-28, IGKV1D-17, IGKV3-7, IGKV2-30, IGKV2D-29, IGKV1-12, IGKV2-28, IGKV1-27, IGKV1D-39, IGLV2-8, IGKV1D-12 |
immunoglobulin production | 49 | 4.03 | 1.29 × 10−17 | CD22, AICDA, VPREB3, MZB1, IGKV4-1, IGKV6-21, IGKV3D-20, IGKV3D-11, IGKV1D-42, IGLV4-69, IGLV8-61, IGLV4-60, IGLV10-54, IGLV1-50, IGLV5-48, IGLV7-46, IGLV5-45, IGLV1-44, IGLV7-43, IGLV2-33, IGLV2-14, IGLV3-10, IGLV3-9, IGLV4-3, TRDV1, IGKV3D-15, IGKV6D-21, IGKV2D-30, IGKV1-6, IGKV3-20, IGKV1D-33, IGKV1-17, IGKV1-8, IGKV1-16, IGKV2-24, IGKV2D-24, IGKV1-9, IGKV1-39, IGKV2D-28, IGKV1D-17, IGKV3-7, IGKV2-30, IGKV2D-29, IGKV1-12, IGKV2-28, IGKV1-27, IGKV1D-39, IGLV2-8, IGKV1D-12 | |
GO-CC | immunoglobulin complex | 72 | 5.58 | 5.46696 × 10−49 | CD79A, JCHAIN, IGKV4-1, IGKV6-21, IGKV3D-20, IGKV3D-11, IGKV1D-42, IGLV4-69, IGLV8-61, IGLV4-60, IGLV10-54, IGLV1-50, IGLV5-48, IGLV7-46, IGLV5-45, IGLV1-44, IGLV7-43, IGLV2-33, IGLV2-14, IGLV3-10, IGLV3-9, IGLV4-3, IGLC7, IGHA2, IGHA1, IGHV6-1, IGHV2-5, IGHV3-7, IGHV3-11, IGHV3-13, IGHV3-15, IGHV3-21, IGHV3-23, IGHV3-35, IGHV4-39, IGHV3-48, IGHV3-49, IGHV5-51, IGHV3-53, IGHV1-58, IGHV3-66, IGHV3-73, IGKV3D-15, IGHV4-59, IGHV3-74, IGKV6D-21, IGHV3-72, IGKV2D-30, IGKV1-6, IGKV3-20, IGKV1D-33, IGKV1-17, IGKV1-8, IGKV1-16, IGKV2-24, IGKV2D-24, IGKV1-9, IGKV1-39, IGKV2D-28, IGKV1D-17, IGKV3-7, IGKV2-30, IGKV2D-29, IGKV1-12, IGKV2-28, IGKV1-27, IGKV1D-39, IGLL5, IGLV2-8, IGKV1D-12, IGHV7-4-1, IGHV3-64D |
collagen-containing extracellular matrix | 69 | 5.35 | 3.37778 × 10−13 | COL11A1, NTN1, FGFR2, COL19A1, ADAMTS2, CMA1, CTSG, BMP7, LAMA1, SRPX, SRPX2, SFRP1, COMP, WNT2, PTPRZ1, SERPINE1, OGN, CXCL12, COL1A1, COL7A1, ANGPTL1, MFAP2, MMP8, TGFBI, CLU, ITIH5, COL10A1, F13A1, AMELX, FGL2, GDF15, MATN3, ADAMDEC1, CILP, MMRN1, INHBE, DPT, AHSG, HAPLN1, HMCN2, NCAM1, SPARCL1, ABI3BP, ACAN, AZGP1, CLEC3B, EDIL3, SHH, CTHRC1, VWA2, MFAP4, KRT1, TNXB, FGB, ANGPTL7, COL6A5, ZG16, F2, BGN, EMILIN3, ANGPTL5, VWC2, PRELP, ELANE, COL4A6, MFAP5, EGFL6, VIT, MMP28 | |
apical plasma membrane | 68 | 5.28 | 9.77371 × 10−14 | SLC13A2, CEACAM7, DPEP1, CLCA4, CASR, SLC9A3, CYBRD1, ABCB11, CDHR2, CA12, CEACAM1, PTPRH, KCNK2, SLC15A1, SLC4A11, SI, SLC26A3, CDHR5, SLC7A5, AQP8, FOLR1, CLIC5, SLC9A2, PAPPA2, ABCG2, TRPM6, ECRG4, CNTFR, SLC17A1, ATP1B2, SLC6A6, SLC14A2, CBLIF, CD36, PRKG2, SLC4A10, ANK2, SLC17A4, ATP6V0D2, SLC26A2, KCNMA1, KCNB1, SLC5A11, STC1, IL6R, PTH1R, CD300LG, AQP5, CLDN1, SCNN1G, MYO1A, CA4, NAALADL1, SLC22A11, SCNN1B, P2RY1, SLC23A1, KISS1, MAL, SPTBN2, SLC6A19, SLC26A9, OXTR, SAPCD2, P2RY4, P2RX2, SLC6A14, GPIHBP1 | |
cell projection membrane | 51 | 3.95 | 6.88773 × 10−8 | DPEP1, PHLPP2, PSD, SLC9A3, CNGB1, CYBRD1, CDHR2, ITGA8, FAP, CEACAM1, PTPRH, EPB41L3, TESC, SLC26A3, CDHR5, BMX, GABRE, SLC7A5, AQP8, CA9, FOLR1, BVES, GABRG2, ABCG2, TRPM6, ATP1B2, SLC6A6, PDE6A, CD36, SLC17A4, SLC7A11, SLC26A2, KCNB1, PDE9A, S100P, HHIP, GPER1, PRKCB, CA4, FAM107A, P2RY12, DRD5, GAP43, SLC6A19, TSPEAR, ITLN1, DDN, MAPT, CYS1, NME1, SSTR3 | |
monoatomic ion channel complex | 45 | 3.49 | 4.70643 × 10−8 | BEST2, TRPC7, CNGB1, KCNK2, GABRE, SLC17A7, GRIN2D, GRIK5, CLIC5, GABRG2, CASQ2, OLFM3, BEST3, DPP6, SCN7A, CACNG8, BEST4, CNGA3, KCNMB1, SCN2B, KCNA6, GRIA4, SCN3A, KCNJ16, KCNMA1, KCNB1, GRIK3, HTR3A, SCNN1G, SCN11A, SCNN1B, SCN9A, LRRC8E, KCNG3, SCN4B, KCNA3, SLC17A8, GRIN2A, CLCNKB, KCNIP4, HTR3E, GABRD, VWC2, TMEM249, GRIN2B | |
GO-MF | metal ion transmembrane transporter activity | 57 | 4.73 | 8.3773 × 10−8 | SLC13A2, SLC11A1, ATP1A2, SLC9A3, ATP2B3, TRPC7, SLC4A4, KCNK2, SLC4A11, SLC17A7, GRIN2D, GRIK5, CLDN16, SLC9A2, SLC5A7, SLC8A2, TRPM6, SLC17A1, SLC6A6, SNAP25, SCN7A, CACNG8, KCNN3, SLC4A10, KCNMB1, SLC17A4, SCN2B, GPM6A, KCNA6, SCN3A, KCNJ16, KCNMA1, SLC13A3, KCNB1, SLC5A11, GRIK3, SLC30A8, PKD1L2, SCNN1G, TRPV3, SCN11A, SCNN1B, SCN9A, SLC23A1, KCNG3, TMEM37, KCNK3, SCN4B, KCNA3, SLC17A8, SLC9A9, GRIN2A, KCNH8, KCNIP4, SLC30A10, SLC6A14, GRIN2B |
monoatomic ion channel activity | 57 | 4.73 | 1.48449 × 10−7 | CLCA1, CLCA4, BEST2, TRPC7, CNGB1, KCNK2, SLC4A11, GABRE, SLC17A7, GRIN2D, GRIK5, P2RX1, CLIC5, GABRG2, TRPM6, BEST3, SNAP25, SCN7A, CACNG8, BEST4, KCNN3, CNGA3, KCNMB1, SCN2B, GPM6A, KCNA6, GRIA4, SCN3A, KCNJ16, KCNMA1, KCNB1, GRIK3, PKD1L2, HTR3A, SCNN1G, TRPV3, SCN11A, SCNN1B, SCN9A, LRRC8E, KCNG3, TMEM37, KCNK3, ANO5, SLC26A9, SCN4B, KCNA3, SLC17A8, OTOP2, GRIN2A, KCNH8, CLCNKB, KCNIP4, HTR3E, GABRD, P2RX2, GRIN2B | |
glycosaminoglycan binding | 41 | 3.41 | 1.40577 × 10−8 | ANOS1, COL11A1, CCN5, FGFR2, EPYC, SERPIND1, CTSG, BMP7, CEMIP, SFRP1, CCN4, COMP, PTN, CCL8, CCN6, JCHAIN, LYVE1, STAB2, HAPLN1, RSPO2, HABP2, ACAN, PCOLCE2, CLEC3B, SHH, TNXB, RSPO1, CXCL11, CXCL8, CEL, REG3A, ZG16, F2, GREM2, BGN, SLIT3, PRELP, SPOCK3, ELANE, VIT, CCL23 | |
extracellular matrix structural constituent | 37 | 3.07 | 9.57517 × 10−11 | ANOS1, COL11A1, COL19A1, LAMA1, SRPX, SRPX2, COMP, OGN, COL1A1, COL7A1, MFAP2, TGFBI, COL10A1, AMELX, FGL2, MATN3, CHI3L1, CILP, MMRN1, DPT, HAPLN1, HMCN2, ABI3BP, ACAN, EDIL3, CTHRC1, MFAP4, TNXB, FGB, COL6A5, BGN, EMILIN3, MUC6, PRELP, COL4A6, MFAP5, MUC5AC | |
serine-type peptidase activity | 36 | 2.99 | 1.1059 × 10−8 | PRSS22, TLL1, FAP, CMA1, PCSK5, MMP11, CTSG, PRSS33, TPSG1, MMP8, PLAU, PCSK2, MASP1, KLK10, KLK8, DPP6, MMP7, MMP13, TMPRSS13, CORIN, HABP2, MMP3, TMPRSS3, MMP10, TMPRSS5, KLK6, KLK7, PCSK9, F2, RELN, MMP1, ELANE, CFD, PRSS41, PRSS56, PRSS2 | |
serine hydrolase activity | 36 | 2.99 | 1.79471 × 10−8 | PRSS22, TLL1, FAP, CMA1, PCSK5, MMP11, CTSG, PRSS33, TPSG1, MMP8, PLAU, PCSK2, MASP1, KLK10, KLK8, DPP6, MMP7, MMP13, TMPRSS13, CORIN, HABP2, MMP3, TMPRSS3, MMP10, TMPRSS5, KLK6, KLK7, PCSK9, F2, RELN, MMP1, ELANE, CFD, PRSS41, PRSS56, PRSS2 | |
serine-type endopeptidase activity | 34 | 2.82 | 1.19537 × 10−8 | PRSS22, TLL1, FAP, CMA1, PCSK5, MMP11, CTSG, PRSS33, TPSG1, MMP8, PLAU, PCSK2, MASP1, KLK10, KLK8, MMP7, MMP13, TMPRSS13, CORIN, HABP2, MMP3, TMPRSS3, MMP10, TMPRSS5, KLK6, KLK7, PCSK9, F2, MMP1, ELANE, CFD, PRSS41, PRSS56, PRSS2 | |
metallopeptidase activity | 32 | 2.66 | 1.54386 × 10−7 | PDPEP1, CLCA1, CLCA4, TLL1, ADAMTS6, TRHDE, ADAMTS2, MMP11, MEP1A, PAPPA2, MMP8, CPXM2, XPNPEP2, CPA4, ADAMDEC1, CPM, MMP7, MMP13, MEP1B, ADAM12, ADAM33, MMP3, ADAMTS12, CPB1, MMP10, ANPEP, NAALADL1, KLK7, LVRN, MMP1, MMP28, PRSS2 | |
KEGG | Neuroactive ligand-receptor interaction | 61 | 3.87 | 1.61 × 10−11 | CHRM2, OXTR, THRB, NPFFR1, GRIK5, CHRM4, GRIK3, PTH1R, HTR4, ADRA1A, GHR, HTR7, UCN2, ADORA3, CTSG, PRSS2, INSL5, LYNX1, EDN2, AVPR1B, EDN3, GLP2R, NPY1R, TACR2, SSTR2, F2, SSTR3, GABRG2, SSTR5, ADRB3, AGTR1, NPSR1, CALCA, ADCYAP1R1, GRP, LPAR1, GRIN2A, APELA, P2RY4, CNR2, CNR1, NPY, P2RY1, PENK, GABRE, GABRD, DRD5, GRIA4, P2RY14, HTR1D, SCTR, GCG, GRIN2B, APLN, GRIN2D, KISS1, PYY, P2RX2, SST, P2RX1, VIP |
Cytokine-cytokine receptor interaction | 41 | 2.60 | 7.87972 × 10−6 | CCL13, CNTFR, CSF3, CSF2, CXCL8, TNFRSF13B, IL24, CXCR5, CXCL17, CXCL1, CXCL3, CXCL2, CXCL5, GHR, CCL8, TNFRSF17, CCL19, AMH, IL6R, CCR2, IL11, CCL23, TNFRSF12A, CCL21, GDF15, OSM, LIFR, PPBP, INHBA, BMP7, BMP5, INHBE, EDAR, BMP3, IL1A, CXCL11, CXCL12, IL23A, TNFSF9, CCL28, IL17C | |
cAMP signaling pathway | 35 | 2.22 | 3.09924 × 10−6 | CHRM2, OXTR, ADCYAP1R1, HHIP, ATP1A2, HTR4, ADCY5, GRIN2A, PLN, CREB3L3, NPY, PLCE1, TNNI3, CNGA3, AMH, BVES, PRKACB, GRIA4, DRD5, EDN2, EDN3, HTR1D, NPY1R, ATP2B3, GCG, ATP1B2, SSTR2, GRIN2B, GRIN2D, SSTR5, SST, VIP, KCNK2, MYL9, CNGB1 | |
Calcium signaling pathway | 31 | 1.97 | 0.000983789 | CHRM2, OXTR, HTR4, ADRA1A, SLC8A2, MYLK, GRIN2A, HTR7, PLN, FGF20, PLCE1, NOS1, PRKACB, DRD5, PRKCG, AVPR1B, PRKCB, TACR2, ATP2B3, VEGFD, GRIN2B, GRIN2D, ADRB3, P2RX2, P2RX1, FGF19, CASQ2, AGTR1, PLCD4, PLCD1, FGFR2 | |
Cell adhesion molecules | 25 | 1.59 | 8.07266 × 10−5 | NLGN1, NRXN1, VTCN1, CLDN2, CLDN1, CDH3, SLITRK2, MPZ, SLITRK3, CLDN23, NCAM1, MADCAM1, JAM2, NTNG1, CADM3, NEGR1, CLDN11, IGSF11, CLDN14, CLDN8, ITGA8, CNTN1, CNTN2, CLDN16, CD22 |
Name | Genes | |
---|---|---|
GO-BP | production of molecular mediator of immune response | IGKV2-24, IGKV2D-29, IGLV7-43, IGLV8-61 |
immunoglobulin production | IGKV2-24, IGKV2D-29, IGLV7-43, IGLV8-61 | |
GO-CC | immunoglobulin complex | IGKV2-24, IGKV2D-29, IGLV7-43, IGLV8-61 |
collagen-containing extracellular matrix | PRELP | |
apical plasma membrane | CA4 | |
cell projection membrane | CA4, GABRE, NME1, TSPEAR, ITLN1 | |
monoatomic ion channel complex | GABRD, GABRE, GRIK5 | |
GO-MF | metal ion transmembrane transporter activity | GRIK5 |
monoatomic ion channel activity | GABRD, GABRE, GRIK5, CLCA1 | |
glycosaminoglycan binding | PRELP | |
extracellular matrix structural constituent | PRELP | |
serine-type peptidase activity | MMP1, MMP3, TPSG1 | |
serine hydrolase activity | MMP1, MMP3, TPSG1 | |
serine-type endopeptidase activity | MMP1, MMP3, TPSG1 | |
metallopeptidase activity | MMP1, MMP3, CLCA1 | |
IGKV2-24, IGKV2D-29, IGLV7-43, IGLV8-61, PRELP, CA4, GABRE, NME1, TSPEAR, ITLN1, GABRD, GRIK5, CLCA1, MMP1, MMP3, TPSG1 (Summarize: A total of 16 genes) |
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Gao, L.; Tian, Y.; Chen, E. The Construction of a Multi-Gene Risk Model for Colon Cancer Prognosis and Drug Treatments Prediction. Int. J. Mol. Sci. 2024, 25, 3954. https://doi.org/10.3390/ijms25073954
Gao L, Tian Y, Chen E. The Construction of a Multi-Gene Risk Model for Colon Cancer Prognosis and Drug Treatments Prediction. International Journal of Molecular Sciences. 2024; 25(7):3954. https://doi.org/10.3390/ijms25073954
Chicago/Turabian StyleGao, Liyang, Ye Tian, and Erfei Chen. 2024. "The Construction of a Multi-Gene Risk Model for Colon Cancer Prognosis and Drug Treatments Prediction" International Journal of Molecular Sciences 25, no. 7: 3954. https://doi.org/10.3390/ijms25073954
APA StyleGao, L., Tian, Y., & Chen, E. (2024). The Construction of a Multi-Gene Risk Model for Colon Cancer Prognosis and Drug Treatments Prediction. International Journal of Molecular Sciences, 25(7), 3954. https://doi.org/10.3390/ijms25073954