Altmetrics
Downloads
95
Views
31
Comments
0
A peer-reviewed article of this preprint also exists.
supplementary.xlsx (115.22KB )
Submitted:
17 August 2023
Posted:
18 August 2023
You are already at the latest version
Gene | Chromosome | Location based on GRCh37.p13 assembly | Source[https://www.ensembl.org/index.html] | |
---|---|---|---|---|
Start | End | |||
AKT1 | 14 | 105235686 | 105262085 | Ensembl:ENSG00000142208 |
AKT2 | 19 | 40736224 | 40791252 | Ensembl:ENSG00000105221 |
AKT3 | 1 | 243651535 | 244014381 | Ensembl:ENSG00000117020 |
APC | 5 | 112043195 | 112181936 | Ensembl:ENSG00000134982 |
APC2 | 19 | 1450120 | 1473243 | Ensembl:ENSG00000115266 |
APPL1 | 3 | 57261757 | 57307499 | Ensembl:ENSG00000157500 |
ARAF | X | 47420604 | 47431307 | Ensembl:ENSG00000078061 |
AXIN1 | 16 | 337440 | 402723 | Ensembl:ENSG00000103126 |
AXIN2 | 17 | 63524681 | 63557766 | Ensembl:ENSG00000168646 |
BAD | 11 | 64037300 | 64052176 | Ensembl:ENSG00000002330 |
BAX | 19 | 49458132 | 49465055 | Ensembl:ENSG00000087088 |
BCL2 | 18 | 60790579 | 60987002 | Ensembl:ENSG00000171791 |
BIRC5 | 17 | 76210334 | 76221716 | Ensembl:ENSG00000089685 |
BRAF | 7 | 140413128 | 140624729 | Ensembl:ENSG00000157764 |
CASP3 | 4 | 185548850 | 185570601 | Ensembl:ENSG00000164305 |
CASP9 | 1 | 15817896 | 15851285 | Ensembl:ENSG00000132906 |
CCND1 | 11 | 69455924 | 69469242 | Ensembl:ENSG00000110092 |
CTNNB1 | 3 | 41240996 | 41281934 | Ensembl:ENSG00000168036 |
CYCS | 7 | 25158275 | 25164879 | Ensembl:ENSG00000172115 |
DCC | 18 | 49866567 | 51062269 | Ensembl:ENSG00000187323 |
FOS | 14 | 75745531 | 75748933 | Ensembl:ENSG00000170345 |
GSK3B | 3 | 119540168 | 119813294 | Ensembl:ENSG00000082701 |
JUN | 1 | 59246463 | 59249719 | Ensembl:ENSG00000177606 |
KRAS | 12 | 25358180 | 25403863 | Ensembl:ENSG00000133703 |
LEF1 | 4 | 108968704 | 109090088 | Ensembl:ENSG00000138795 |
MAP2K1 | 15 | 66679250 | 66783882 | Ensembl:ENSG00000169032 |
MAPK1 | 22 | 22113946 | 22221970 | Ensembl:ENSG00000100030 |
MAPK10 | 4 | 86931558 | 87374348 | Ensembl:ENSG00000109339 |
MAPK3 | 16 | 30125426 | 30134541 | Ensembl:ENSG00000102882 |
MAPK8 | 10 | 49514720 | 49647403 | Ensembl:ENSG00000107643 |
MAPK9 | 5 | 179660143 | 179719083 | Ensembl:ENSG00000050748 |
MLH1 | 3 | 3703500 | 37092337 | Ensembl:ENSG00000076242 |
MSH2 | 2 | 47630206 | 47710367 | Ensembl:ENSG00000095002 |
MSH3 | 5 | 79950471 | 80172634 | Ensembl:ENSG00000113318 |
MSH6 | 2 | 48010284 | 48034092 | Ensembl:ENSG00000116062 |
MYC | 8 | 128747680 | 128755197 | Ensembl:ENSG00000136997 |
PIK3CA | 3 | 178866145 | 178957881 | Ensembl:ENSG00000121879 |
PIK3CB | 3 | 138371540 | 138553770 | Ensembl:ENSG00000051382 |
PIK3CD | 1 | 9711789 | 9789172 | Ensembl:ENSG00000171608 |
PIK3CG | 7 | 106505727 | 106549425 | Ensembl:ENSG00000105851 |
PIK3R1 | 5 | 67511584 | 67597649 | Ensembl:ENSG00000145675 |
PIK3R2 | 19 | 18263973 | 18281342 | Ensembl:ENSG00000105647 |
PIK3R3 | 1 | 46505812 | 46640573 | Ensembl:ENSG00000117461 |
PIK3R5 | 17 | 8782233 | 8869024 | Ensembl:ENSG00000141506 |
RAC1 | 7 | 6414158 | 6443598 | Ensembl:ENSG00000136238 |
RAC2 | 22 | 37621310 | 37640309 | Ensembl:ENSG00000128340 |
RAC3 | 17 | 79989554 | 79992080 | Ensembl:ENSG00000169750 |
RAF1 | 3 | 12625100 | 12705616 | Ensembl:ENSG00000132155 |
RALGDS | 9 | 135973109 | 136024597 | Ensembl:ENSG00000160271 |
RHOA | 3 | 49396578 | 49449409 | Ensembl:ENSG00000067560 |
SMAD2 | 18 | 45335328 | 45457243 | Ensembl:ENSG00000175387 |
SMAD3 | 15 | 67357940 | 67487507 | Ensembl:ENSG00000166949 |
SMAD4 | 18 | 48556583 | 48611412 | Ensembl:ENSG00000141646 |
TCF7 | 5 | 133450372 | 133483901 | Ensembl:ENSG00000081059 |
TCF7L1 | 2 | 85360515 | 85537510 | Ensembl:ENSG00000152284 |
TCF7L2 | 10 | 114710006 | 114927437 | Ensembl:ENSG00000148737 |
TGFB1 | 19 | 41836228 | 41859827 | Ensembl:ENSG00000105329 |
TGFB2 | 1 | 218518678 | 218617961 | Ensembl:ENSG00000092969 |
TGFB3 | 14 | 76424440 | 76449354 | Ensembl:ENSG00000119699 |
TGFBR1 | 9 | 101867395 | 101916474 | Ensembl:ENSG00000106799 |
TGFBR2 | 3 | 30647994 | 30735634 | Ensembl:ENSG00000163513 |
TP53 | 17 | 7571739 | 7590808 | Ensembl:ENSG00000141510 |
Pathway | KEGG CRC genes | References [https://www.genome.jp] |
---|---|---|
Cell cycle | CCND1, GSK3B, MYC, SMAD2, SMAD3, SMAD4, TGFB1, TGFB2, TGFB3, TP53 | https://www.genome.jp/pathway/hsa04110 |
p53 signaling pathway | BAX, BCL2, CASP3, CASP9, CCND1, CYCS, TP53 | https://www.genome.jp/pathway/hsa04115 |
Apoptosis | AKT1, AKT2, AKT3, BAD, BAX, BCL2, BIRC5, CASP3, CASP9, CYCS, FOS, JUN, KRAS, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, PIK3CA, PIK3CB, PIK3CD, PIK3R1, PIK3R2, PIK3R3, RAF1, TP53, DCC, APPL1 | https://www.genome.jp/pathway/hsa04210 |
mTOR signaling pathway | BRAF, GSK3B, KRAS, MAP2K1, MAPK1, PIK3CA, PIK3CB, PIK3CD, PIK3R1, PIK3R2, PIK3R3, RAF1, RHOA | https://www.genome.jp/pathway/hsa04150 |
PI3K-Akt signaling pathway | AKT1, AKT2, AKT3, BAD, BCL2, CASP9, GSK3B, KRAS, MAP2K1, MAPK1, MAPK3, MYC, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, RAC1, RAF1, TP53 | https://www.genome.jp/pathway/hsa04151 |
Wnt signaling pathway | APC, APC2, AXIN1, AXIN2, CCND1,CTNNB1, GSK3B, JUN, LEF1, MAPK10, MAPK8, MAPK9, MYC, RAC1, RAC2, RAC3, RHOA, SMAD3, SMAD4, TCF7, TCF7L1, TCF7L2, TP53 | https://www.genome.jp/pathway/hsa04310 |
TGF-beta signaling pathway | MAPK1, MAPK3, MYC, RHOA, SMAD2, SMAD3, SMAD4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, | https://www.genome.jp/pathway/hsa04350 |
MAPK signaling pathway | AKT1, AKT2, AKT3, ARAF, BRAF, CASP3, FOS, JUN, KRAS, LEF1, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MYC, RAC1, RAC2, RAC3, RAF1, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TP53 | https://www.genome.jp/pathway/hsa04010 |
ErbB signaling pathway | AKT1, AKT2, AKT3, ARAF, BAD, BRAF, GSK3B, JUN, KRAS, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MYC, PIK3CA, PIK3CB, PIK3CD, PIK3R1, PIK3R2, PIK3R3, RAF | https://www.genome.jp/pathway/hsa04012 |
MSI pathway | APC, AXIN1, AXIN2, BAD, BAX, BCL2, GSK3B, MLH1, MSH2, MSH3, MSH6, TGFBR2 | https://www.genome.jp/dbget-bin/www_bget?path:map05210 |
Ras signaling pathway | AKT1, AKT2, AKT3, BAD, KRAS, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, PIK3CA, PIK3CB, PIK3CD, PIK3R1, PIK3R2, PIK3R3, RAC1, RAC2, RAC3, RAF1, RALGDS, RHOA | https://www.genome.jp/pathway/hsa04014 |
Characteristics | Number of patients (Ν=237) | % |
---|---|---|
Median age (range) | 64 (18–84) | |
<70 | 159 | 67.1 |
≥70 | 78 | 32.9 |
Gender | ||
Males | 151 | 63.7 |
Females | 86 | 36.3 |
Tumor location | ||
Cecum | 38 | 16.0 |
Ascending | 42 | 17.7 |
Transverse | 22 | 9.3 |
Descending | 24 | 10.1 |
Sigmoid | 111 | 46.8 |
Sidedness | ||
Left | 158 | 66.7 |
Right | 79 | 33.3 |
Performance status | ||
0-1 | 236 | 99.6 |
>2 | 1 | .4 |
Regimen | ||
Folfox | 105 | 44.3 |
Capox | 132 | 55.7 |
Treatment duration | ||
3 months | 116 | 48.9 |
6 months | 121 | 51.1 |
Gene | Mutant patients |
---|---|
AKT1 | 6 |
AKT2 | 3 |
AKT3 | 3 |
APC | 181 |
APC2 | 38 |
APPL1 | 19 |
ARAF | 8 |
AXIN1 | 11 |
AXIN2 | 61 |
BAD | 2 |
BAX | 14 |
BCL2 | 2 |
BIRC5 | 70 |
BRAF | 15 |
CASP3 | 0 |
CASP9 | 62 |
CCND1 | 3 |
CTNNB1 | 7 |
CYCS | 1 |
DCC | 62 |
FOS | 2 |
GSK3B | 2 |
JUN | 5 |
KRAS | 80 |
LEF1 | 3 |
MAP2K1 | 2 |
MAPK1 | 4 |
MAPK10 | 3 |
MAPK3 | 0 |
MAPK8 | 4 |
MAPK9 | 3 |
MLH1 | 55 |
MSH2 | 6 |
MSH3 | 110 |
MSH6 | 51 |
MYC | 11 |
PIK3CA | 62 |
PIK3CB | 8 |
PIK3CD | 11 |
PIK3CG | 48 |
PIK3R1 | 23 |
PIK3R2 | 70 |
PIK3R3 | 0 |
PIK3R5 | 9 |
RAC1 | 0 |
RAC2 | 0 |
RAC3 | 11 |
RAF1 | 1 |
RALGDS | 42 |
RHOA | 6 |
SMAD2 | 3 |
SMAD3 | 14 |
SMAD4 | 25 |
TCF7 | 35 |
TCF7L1 | 61 |
TCF7L2 | 39 |
TGFB1 | 74 |
TGFB2 | 11 |
TGFB3 | 2 |
TGFBR1 | 16 |
TGFBR2 | 25 |
TP53 | 148 |
Characteristics | Gene | No % (p value) |
---|---|---|
Gender | ||
Male vs Female | JUN | 43.4% vs 25.0% (0.05) |
MAPK3 | 57.5% vs 31.1% (0.05) | |
Sideness | ||
Left vs Right | MLH1 | 80% vs 20% (0.007) |
MSH6 | 84.3% vs 15.7% (0.001) | |
TCF7L1 | 77% vs 33% (0.019) | |
Location | ||
Colon vs Sigmoid | DCC | 90.3% vs 9.7% (0.04) |
KRAS | 88.8% vs 11.2% (0.048) | |
TGFBR2 | 96% vs 4% (0.043) | |
Age | ||
<70 vs ≥70 | TGFBR1 | 57.5% vs 33% (0.012) |
51-70 vs ≥70 vs <50 | BAD | 56.1% vs 30.7% vs 12.7% (<0.001) |
51-70 vs ≥70 vs <50 | RAC | 56.1% vs 30.7% vs 12.7% (0.016) |
51-70 vs ≥70 vs <50 | AKT, AKT2, AKT3, APC, APPL1, AXIN1, AXIN2, BIRC5, DCC, GSK3B, KRAS, MAPK1, MAPK8, MAPK9, MAPK10, MLH1, MSH6, PIK3CA, PIK3R1, PIK3R2, PIK3R3, PIK3R5, RAF1, RALGD5, SMAD2, SMAD3, TCF7L2, TGFB1, TGFB2 | 56.1% vs 30.7% vs 12.7% (0.037) |
Relapse post Adj Chemotherapy | ||
Yes vs No | ARAF, MAPK10 | 71.7% vs 20.5% (0.027) |
CASP3 | 75.5% vs 22.6% (0.044) | |
TCF7 | 75% vs 21.2% (0.003) | |
TGFΒ3 | 74.5% vs 22.2% (0.037) |
Cell cycle | Apoptosis | PI3K-Akt | Wnt | MAPK | ErbB | MSI | RAS | |
---|---|---|---|---|---|---|---|---|
Transverse Colon | X | X | X | X | ||||
TaqI Homozygous | X | X | X | X | X | X | X | |
ApaI Homozygous | X | X | X | X | ||||
FokI Homozygous | X | X | X | |||||
BsmI Homozygous | X | X | X | |||||
TLR9 -T1237C Homozygous | X | X | X | |||||
TLR9–T1486C Homozygous | X | X | X |
Univariate | Multivariate | |||||||
---|---|---|---|---|---|---|---|---|
DFS | OS | DFS | OS | |||||
Feature | HR (95%CI) | p-value | HR (95%CI) | p-value | HR (95%CI) | p-value | HR (95%CI) | p-value |
Sidedness (Right vs Left) | 1.9 (1.2–3.2) | 0.012 | 2.1 (1.0–4.0) | 0.043 | 2.1 (1.1-4.0) | 0.019 | 2.2 (1.0-4.5) | 0.043 |
AKT1 (Mutant vs Wild type) | 2.9 (1.1-8.2) | 0.039 | ||||||
APC2 (Mutant vs Wild type) | 2.5 (1.4-4.5) | 0.002 | ||||||
ARAF (Mutant vs Wild type) | 3.8 (1.2-12.1) | 0.027 | 5.0 (2.0-12.7) | 0.001 | 3.9 (1.2-13.1) | 0.027 | ||
BAD (Mutant vs Wild type) | 8.6 (1.1-64.4) | 0.036 | ||||||
MAPK10 (Mutant vs Wild type) | 43.0 (9.1-203.7) | <0.001 | 15.1 (4.6-50.3) | <0.001 | 49.0 (9.8-244.1) | <0.001 | ||
MSH6 (Wild type vs Mutant) | 2.3 (1.0-5.1) | 0.041 | ||||||
RAC3 (Mutant vs Wild type) | 4.7 (1.8-11.9) | 0.001 | 3.5 (1.1-10.7) | 0.029 | ||||
RHOA (Mutant vs Wild type) | 4.8 (1.5-15.6) | 0.009 | 9.5 (1.9-47.7) | 0.006 | ||||
TGFB2 (Mutant vs Wild type) | 2.6 (1.1-6.7) | 0.040 | ||||||
TGFB3 (Mutant vs Wild type) | 9.0 (2.1-37.8) | 0.003 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 MDPI (Basel, Switzerland) unless otherwise stated