Introduction
Methods
Study participants
RNA processing
mRNA:RNA-seq sequencing library preparation and data processing
miRNA
NF-κB signalling genes
Statistical methods
Bioinformatics analysis
Results
N
| % | |
---|---|---|
Site | ||
Colon | 169 | 77.9 |
Rectal | 48 | 22.1 |
Sex | ||
Male | 118 | 54.4 |
Female | 99 | 45.6 |
Age | ||
Mean (SD) | 64.8 | 10.1 |
Race | ||
Non-Hispanic White | 161 | 74.2 |
Hispanic | 14 | 6.5 |
Non-Hispanic Black | 8 | 3.7 |
Unknown | 34 | 15.7 |
Tumour phenotype | ||
TP53 mutated | 103 | 47.5 |
KRAS mutated | 69 | 31.8 |
BRAF-mutated | 21 | 10.1 |
CIMP High | 45 | 20.7 |
MSI | 29 | 13.4 |
Gene name | Tumour mean | Normal mean | Fold change | Raw P value | FDR P value |
---|---|---|---|---|---|
CCL13
| 0.71 | 6.30 | 0.11 | 1.70E−23 | 8.68E−23 |
CCL19
| 1.02 | 7.03 | 0.14 | 7.29E−23 | 3.53E−22 |
PRKCB
| 14.65 | 53.12 | 0.28 | 1.52E−41 | 3.49E−40 |
TNFRSF13C
| 1.72 | 5.88 | 0.29 | 1.43E−16 | 4.88E−16 |
CD40LG
| 1.00 | 3.33 | 0.30 | 9.05E−17 | 3.33E−16 |
CXCL12
| 23.04 | 74.27 | 0.31 | 7.44E−49 | 2.28E−47 |
PLCG2
| 16.91 | 52.18 | 0.32 | 1.31E−36 | 2.00E−35 |
BTK
| 5.16 | 15.34 | 0.34 | 4.95E−25 | 2.87E−24 |
CCL21
| 5.84 | 16.77 | 0.35 | 4.21E−16 | 1.38E−15 |
BCL2
| 24.42 | 62.11 | 0.39 | 3.73E−39 | 6.86E−38 |
ZAP70
| 7.77 | 18.76 | 0.41 | 1.51E−21 | 6.95E−21 |
LTB
| 3.10 | 7.26 | 0.43 | 3.88E−13 | 1.11E−12 |
BLNK
| 20.68 | 47.50 | 0.44 | 2.98E−27 | 2.11E−26 |
TNFRSF11A
| 53.68 | 118.87 | 0.45 | 2.30E−21 | 1.01E−20 |
LTA
| 0.61 | 1.26 | 0.48 | 1.13E−04 | 2.00E−04 |
LBP
| 0.15 | 0.28 | 0.53 | 3.39E−02 | 4.72E−02 |
LAT
| 7.72 | 12.01 | 0.64 | 6.19E−10 | 1.54E−09 |
CD40
| 16.05 | 24.91 | 0.64 | 1.97E−08 | 4.31E−08 |
IL1R1
| 57.71 | 89.40 | 0.65 | 9.55E−17 | 3.38E−16 |
TNFSF14
| 6.37 | 9.76 | 0.65 | 3.20E−06 | 6.01E−06 |
MAP3K14
| 33.86 | 51.73 | 0.65 | 1.46E−24 | 7.90E−24 |
BIRC3
| 79.53 | 120.36 | 0.66 | 1.83E−14 | 5.42E−14 |
CD14
| 9.64 | 14.13 | 0.68 | 1.36E−07 | 2.84E−07 |
CFLAR
| 203.49 | 290.53 | 0.70 | 2.89E−29 | 2.42E−28 |
RIPK1
| 49.35 | 69.68 | 0.71 | 1.19E−19 | 4.57E−19 |
LY96
| 0.91 | 1.25 | 0.73 | 9.16E−02 | 1.15E−01 |
TNFRSF1A
| 90.65 | 118.74 | 0.76 | 4.32E−20 | 1.81E−19 |
ATM
| 239.32 | 312.70 | 0.77 | 4.82E−16 | 1.53E−15 |
BCL10
| 42.63 | 55.30 | 0.77 | 4.62E−09 | 1.06E−08 |
NFKBIA
| 58.77 | 75.03 | 0.78 | 1.13E−07 | 2.41E−07 |
LCK
| 8.55 | 10.61 | 0.81 | 2.13E−02 | 3.06E−02 |
TIRAP
| 21.76 | 26.81 | 0.81 | 3.76E−06 | 6.91E−06 |
PIAS4
| 29.27 | 35.75 | 0.82 | 6.64E−07 | 1.33E−06 |
BIRC2
| 81.92 | 98.12 | 0.83 | 6.71E−10 | 1.63E−09 |
PRKCQ
| 7.27 | 8.69 | 0.84 | 3.63E−02 | 4.99E−02 |
VCAM1
| 13.23 | 15.65 | 0.85 | 3.98E−02 | 5.37E−02 |
RELB
| 24.80 | 28.79 | 0.86 | 1.24E−03 | 1.96E−03 |
TNFSF13B
| 4.40 | 5.11 | 0.86 | 9.98E−02 | 1.24E−01 |
TRADD
| 25.11 | 28.92 | 0.87 | 2.47E−03 | 3.79E−03 |
TAB2
| 128.75 | 146.44 | 0.88 | 8.45E−07 | 1.65E−06 |
TAB1
| 29.01 | 32.68 | 0.89 | 1.36E−03 | 2.13E−03 |
TRAF1
| 46.52 | 51.87 | 0.90 | 1.55E−02 | 2.26E−02 |
TRIM25
| 136.97 | 150.69 | 0.91 | 2.32E−04 | 3.89E−04 |
ERC1
| 140.89 | 154.24 | 0.91 | 2.57E−03 | 3.88E−03 |
NFKB2
| 45.18 | 49.11 | 0.92 | 5.89E−02 | 7.74E−02 |
NFKB1
| 77.63 | 83.98 | 0.92 | 7.65E−03 | 1.14E−02 |
CARD10
| 73.25 | 78.85 | 0.93 | 7.35E−02 | 9.39E−02 |
PIDD
| 28.99 | 31.19 | 0.93 | 1.08E−01 | 1.33E−01 |
DDX58
| 45.26 | 48.56 | 0.93 | 1.77E−01 | 2.06E−01 |
IKBKB
| 137.36 | 145.80 | 0.94 | 6.63E−02 | 8.59E−02 |
TNF
| 1.95 | 2.04 | 0.96 | 7.52E−01 | 7.60E−01 |
PTGS2
| 16.66 | 17.36 | 0.96 | 6.99E−01 | 7.14E−01 |
TRAF3
| 34.10 | 35.38 | 0.96 | 3.16E−01 | 3.54E−01 |
TNFAIP3
| 100.76 | 104.33 | 0.97 | 4.13E−01 | 4.38E−01 |
TICAM1
| 23.76 | 24.47 | 0.97 | 5.30E−01 | 5.54E−01 |
MYD88
| 64.07 | 65.97 | 0.97 | 4.14E−01 | 4.38E−01 |
IRAK4
| 39.76 | 40.57 | 0.98 | 5.92E−01 | 6.11E−01 |
MALT1
| 75.70 | 75.80 | 1.00 | 9.69E−01 | 9.69E−01 |
TRAF6
| 38.06 | 36.78 | 1.03 | 3.37E−01 | 3.74E−01 |
GADD45B
| 12.90 | 12.05 | 1.07 | 3.43E−01 | 3.76E−01 |
TICAM2
| 8.19 | 7.62 | 1.08 | 2.73E−01 | 3.10E−01 |
CARD11
| 21.22 | 19.62 | 1.08 | 3.93E−01 | 4.26E−01 |
LTBR
| 126.02 | 113.31 | 1.11 | 1.41E−04 | 2.44E−04 |
IKBKG
| 6.91 | 6.20 | 1.11 | 2.04E−01 | 2.35E−01 |
CSNK2B
| 78.25 | 70.03 | 1.12 | 2.92E−04 | 4.80E−04 |
CARD14
| 12.91 | 11.54 | 1.12 | 1.12E−01 | 1.35E−01 |
RELA
| 82.20 | 73.32 | 1.12 | 5.56E−06 | 1.00E−05 |
SYK
| 111.40 | 98.12 | 1.14 | 1.73E−04 | 2.94E−04 |
MAP3K7
| 72.49 | 62.09 | 1.17 | 9.69E−07 | 1.86E−06 |
CHUK
| 44.48 | 37.81 | 1.18 | 4.50E−04 | 7.26E−04 |
TNFSF11
| 4.36 | 3.64 | 1.20 | 1.30E−01 | 1.56E−01 |
XIAP
| 187.63 | 156.09 | 1.20 | 8.16E−13 | 2.21E−12 |
IL1B
| 22.58 | 18.76 | 1.20 | 2.65E−02 | 3.74E−02 |
TAB3
| 134.33 | 108.39 | 1.24 | 2.64E−09 | 6.22E−09 |
BCL2A1
| 2.01 | 1.61 | 1.25 | 1.59E−01 | 1.87E−01 |
CCL4
| 2.74 | 2.06 | 1.33 | 4.03E−02 | 5.37E−02 |
TRAF2
| 40.20 | 29.46 | 1.36 | 8.02E−13 | 2.21E−12 |
PARP1
| 109.63 | 79.73 | 1.37 | 5.66E−16 | 1.74E−15 |
ICAM1
| 47.42 | 34.43 | 1.38 | 3.56E−07 | 7.28E−07 |
TLR4
| 51.80 | 37.22 | 1.39 | 1.72E−08 | 3.86E−08 |
LYN
| 48.21 | 33.32 | 1.45 | 2.29E−12 | 5.85E−12 |
CSNK2A1
| 138.89 | 92.92 | 1.49 | 5.00E−25 | 2.87E−24 |
UBE2I
| 91.18 | 61.00 | 1.49 | 9.53E−33 | 1.25E−31 |
PLCG1
| 199.37 | 118.93 | 1.68 | 8.50E−31 | 8.69E−30 |
TRAF5
| 185.37 | 108.42 | 1.71 | 3.65E−29 | 2.80E−28 |
CSNK2A2
| 46.72 | 23.14 | 2.02 | 1.14E−30 | 1.05E−29 |
CSNK2A1P
| 1.98 | 0.91 | 2.17 | 1.29E−12 | 3.39E−12 |
IRAK1
| 184.02 | 82.28 | 2.24 | 1.90E−54 | 8.76E−53 |
BCL2L1
| 144.28 | 64.05 | 2.25 | 1.06E−56 | 9.73E−55 |
PLAU
| 54.21 | 21.51 | 2.52 | 6.31E−31 | 7.25E−30 |
CXCL2
| 27.61 | 10.82 | 2.55 | 9.88E−20 | 3.95E−19 |
IL8
| 37.68 | 7.35 | 5.12 | 1.13E−25 | 7.46E−25 |
Gene name | Tumour mean | Normal mean | Fold change | miRNA | Tumour mean | Normal mean | Fold change | Raw p value | FDR p value |
---|---|---|---|---|---|---|---|---|---|
BTK | 5.16 | 15.34 | 0.34 |
hsa-miR-150-5p
a
| 14.90 | 39.17 | 0.38 | < 0.0001 | 0.0116 |
hsa-miR-203a
| 12.52 | 3.70 | 3.38 | < 0.0001 | 0.0116 | ||||
hsa-miR-20b-5p
| 17.65 | 3.30 | 5.35 | < 0.0001 | 0.0116 | ||||
hsa-miR-650 | 4.51 | 16.60 | 0.27 | < 0.0001 | 0.0116 | ||||
CSNK2A2 | 46.72 | 23.14 | 2.02 |
hsa-miR-20b-5p
| 17.65 | 3.30 | 5.35 | < 0.0001 | 0.0271 |
hsa-miR-6515-5p | 1.20 | 4.41 | 0.27 | < 0.0001 | 0.0271 | ||||
hsa-miR-92a-3p | 121.60 | 41.18 | 2.95 | < 0.0001 | 0.0271 | ||||
TRAF5 | 185.37 | 108.42 | 1.71 |
hsa-miR-1271-5p
| 1.28 | 2.35 | 0.55 | < 0.0001 | 0.0349 |
hsa-miR-146a-5p | 10.73 | 6.93 | 1.55 | 0.0007 | 0.0438 | ||||
hsa-miR-29a-3p
| 110.29 | 51.04 | 2.16 | 0.0006 | 0.0438 | ||||
hsa-miR-378g | 1.19 | 2.46 | 0.48 | 0.0007 | 0.0438 | ||||
hsa-miR-3923 | 0.29 | 1.66 | 0.18 | 0.0003 | 0.0349 | ||||
hsa-miR-520d-3p | 1.74 | 2.76 | 0.63 | < 0.0001 | 0.0349 | ||||
hsa-miR-5685 | 1.28 | 2.78 | 0.46 | 0.0003 | 0.0349 | ||||
hsa-miR-92a-3p | 121.60 | 41.18 | 2.95 | 0.0003 | 0.0349 | ||||
CD40 | 16.05 | 24.91 | 0.64 | hsa-miR-150-5p | 14.90 | 39.17 | 0.38 | < 0.0001 | 0.0136 |
hsa-miR-650 | 4.51 | 16.60 | 0.27 | < 0.0001 | 0.0136 | ||||
CXCL12 | 23.04 | 74.27 | 0.31 |
hsa-miR-133b
| 1.71 | 6.94 | 0.25 | 0.0005 | 0.037 |
hsa-miR-145-5p | 132.97 | 223.14 | 0.60 | 0.0003 | 0.037 | ||||
hsa-miR-150-5p
| 14.90 | 39.17 | 0.38 | 0.0005 | 0.037 | ||||
hsa-miR-193b-3p | 9.12 | 5.42 | 1.68 | < 0.0001 | 0.0326 | ||||
hsa-miR-195-5p | 3.59 | 12.18 | 0.29 | 0.0002 | 0.0326 | ||||
hsa-miR-497-5p | 1.77 | 7.12 | 0.25 | 0.0002 | 0.0326 | ||||
ZAP70 | 7.77 | 18.76 | 0.41 | hsa-miR-150-5p | 14.90 | 39.17 | 0.38 | < 0.0001 | 0.0407 |
IL1R1 | 57.71 | 89.40 | 0.65 | hsa-miR-193b-3p | 9.12 | 5.42 | 1.68 | < 0.0001 | 0.0203 |
hsa-miR-214-3p
| 13.24 | 6.13 | 2.16 | 0.0003 | 0.0407 | ||||
PLAU | 54.21 | 21.51 | 2.52 |
hsa-miR-215
| 49.53 | 77.27 | 0.64 | 0.0002 | 0.0407 |
hsa-miR-934 | 4.36 | 0.94 | 4.66 | < 0.0001 | 0.0407 | ||||
PLCG1 | 199.37 | 118.93 | 1.68 |
hsa-miR-1246
| 629.21 | 412.81 | 1.52 | 0.0004 | 0.0271 |
hsa-miR-130b-3p | 8.74 | 4.89 | 1.79 | 0.0007 | 0.0305 | ||||
hsa-miR-17-5p
| 61.04 | 16.38 | 3.73 | 0.0009 | 0.0305 | ||||
hsa-miR-196b-5p | 17.89 | 5.53 | 3.24 | 0.0009 | 0.0305 | ||||
hsa-miR-20a-5p
| 70.78 | 17.61 | 4.02 | 0.0009 | 0.0305 | ||||
hsa-miR-20b-5p
| 17.65 | 3.30 | 5.35 | 0.0006 | 0.0305 | ||||
hsa-miR-25-3p | 30.05 | 12.78 | 2.35 | 0.0005 | 0.0291 | ||||
hsa-miR-375
| 20.50 | 54.53 | 0.38 | 0.0014 | 0.0407 | ||||
hsa-miR-424-3p | 39.81 | 25.37 | 1.57 | < 0.0001 | 0.0163 | ||||
hsa-miR-583
| 6.61 | 3.22 | 2.05 | 0.0009 | 0.0305 | ||||
hsa-miR-663b | 65.50 | 32.21 | 2.03 | 0.0009 | 0.0305 | ||||
hsa-miR-92a-3p | 121.60 | 41.18 | 2.95 | < 0.0001 | 0.0163 | ||||
CCL21 | 5.84 | 16.77 | 0.35 | hsa-miR-150-5p | 14.90 | 39.17 | 0.38 | < 0.0001 | 0.0203 |
hsa-miR-195-5p | 3.59 | 12.18 | 0.29 | < 0.0001 | 0.0203 | ||||
hsa-miR-203a | 12.52 | 3.70 | 3.38 | 0.0002 | 0.0233 | ||||
hsa-miR-497-5p | 1.77 | 7.12 | 0.25 | 0.0002 | 0.0233 | ||||
hsa-miR-650 | 4.51 | 16.60 | 0.27 | 0.0002 | 0.0233 | ||||
TNFRSF11A | 53.68 | 118.87 | 0.45 |
hsa-miR-17-5p
| 61.04 | 16.38 | 3.73 | 0.0021 | 0.0342 |
hsa-miR-193b-3p | 9.12 | 5.42 | 1.68 | < 0.0001 | 0.0063 | ||||
hsa-miR-196b-5p
| 17.89 | 5.53 | 3.24 | < 0.0001 | 0.0063 | ||||
hsa-miR-199a-5p
| 20.18 | 9.28 | 2.17 | 0.0007 | 0.0178 | ||||
hsa-miR-20b-5p
| 17.65 | 3.30 | 5.35 | 0.0006 | 0.0158 | ||||
hsa-miR-214-3p
| 13.24 | 6.13 | 2.16 | 0.0004 | 0.0125 | ||||
hsa-miR-330-3p
| 2.81 | 5.59 | 0.50 | 0.0015 | 0.0284 | ||||
hsa-miR-361-5p | 11.62 | 6.20 | 1.87 | 0.0015 | 0.0284 | ||||
hsa-miR-365a-3p
| 8.43 | 4.33 | 1.94 | < 0.0001 | 0.0063 | ||||
hsa-miR-375
| 20.50 | 54.53 | 0.38 | 0.0002 | 0.0081 | ||||
hsa-miR-424-3p | 39.81 | 25.37 | 1.57 | 0.0004 | 0.0125 | ||||
hsa-miR-590-5p
| 1.78 | 3.04 | 0.59b
| 0.0029 | 0.0414 | ||||
hsa-miR-663b
| 65.50 | 32.21 | 2.03 | 0.0005 | 0.0151 | ||||
hsa-miR-92a-3p | 121.60 | 41.18 | 2.95 | 0.0002 | 0.0081 | ||||
hsa-miR-934
| 4.36 | 0.94 | 4.66 | 0.0002 | 0.0081 | ||||
PRKCB | 14.65 | 53.12 | 0.28 |
hsa-miR-150-5p
| 14.90 | 39.17 | 0.38 | < 0.0001 | 0.0102 |
hsa-miR-203a
| 12.52 | 3.70 | 3.38 | < 0.0001 | 0.0102 | ||||
hsa-miR-650 | 4.51 | 16.60 | 0.27 | < 0.0001 | 0.0102 | ||||
BCL2L1 | 144.28 | 64.05 | 2.25 | hsa-miR-92a-3p | 121.60 | 41.18 | 2.95 | < 0.0001 | 0.0407 |
BCL2 | 24.42 | 62.11 | 0.39 |
hsa-miR-150-5p
| 14.90 | 39.17 | 0.38 | < 0.0001 | 0.0203 |
hsa-miR-195-5p
| 3.59 | 12.18 | 0.29 | 0.0003 | 0.0488 | ||||
hsa-miR-203a
| 12.52 | 3.70 | 3.38 | < 0.0001 | 0.0203 | ||||
hsa-miR-650
| 4.51 | 16.60 | 0.27 | < 0.0001 | 0.0203 | ||||
CCL13 | 0.71 | 6.30 | 0.11 | hsa-miR-221-3p | 13.53 | 4.12 | 3.28 | < 0.0001 | 0.0271 |
hsa-miR-324-5p
| 5.20 | 2.27 | 2.29 | 0.0004 | 0.0452 | ||||
hsa-miR-34a-5p | 25.15 | 12.32 | 2.04 | 0.0004 | 0.0452 | ||||
PLCG2 | 16.91 | 52.18 | 0.32 |
hsa-miR-150-5p
| 14.90 | 39.17 | 0.38 | < 0.0001 | 0.0163 |
hsa-miR-195-5p
| 3.59 | 12.18 | 0.29 | 0.0002 | 0.0203 | ||||
hsa-miR-203a
| 12.52 | 3.70 | 3.38 | 0.0002 | 0.0203 | ||||
hsa-miR-429
| 13.33 | 8.29 | 1.61 | 0.0005 | 0.0407 | ||||
hsa-miR-650 | 4.51 | 16.60 | 0.27 | < 0.0001 | 0.0163 |
miRNA | Genes with seed-region match | Genes without seed-region match |
---|---|---|
miR-1246 |
PLCG1
| |
miR-1271-5p |
TRAF5
| |
miR-130b-3p |
PLCG1
| |
miR-133b |
CXCL12
| |
miR-145-5p |
CXCL12
| |
miR-146a-5p |
TRAF5
| |
miR-150-5p |
BTK, CXCL2, PRKCB, BCL2, PLCG2, |
CD40, ZAP70, CCL21
|
miR-17-5p |
PLCG1, TNFRSF11A
| |
miR-193b-3p |
CXCL12, TNFRSF11A, IL1R1
| |
miR-195-5p |
BCL2. PLCG2
|
CXCL12, CCL21
|
miR-196b-5p |
TNFRSF11A
|
PLCG1
|
miR-199a-5p |
TNFRSF11A
| |
miR-203a |
BTK, PRKCB, BCL2, PLCG2
|
CCL21
|
miR-20a-5p |
PLCG1
| |
miR-20b-5p |
BTK, CSNK2A2, PLCG1, TNFRSF11A
| |
miR-214-3p |
IL1R1, TNFRSF11A
| |
miR-215 |
PLAU
| |
miR-221-3p |
CCL13
| |
miR-25-3p |
PLCG1
| |
miR-29a-3p |
TRAF5
| |
miR-324-5p |
CCL13
| |
miR-330-3p |
TNFRSF11A
| |
miR-34a-5p |
CCL13
| |
miR-361-5p |
TNFRSF11A
| |
miR-365a-3p |
TNFRSF11A
| |
miR-375 |
PLCG1, TNFRSF11A
| |
miR-378g |
TRAF5
| |
miR-3923 |
TRAF5
| |
miR-424-3p |
PLCG1, TNFRSF11A
| |
miR-429 |
PLCG2
| |
miR-497-5p |
CXCL12, CCL21
| |
miR-520d-3p |
TRAF5
| |
miR-5685 |
TRAF5
| |
miR-583 |
PLCG1
| |
miR-590-5p |
TNFRSF11A
| |
miR-650 |
BLC2
|
BTK, CD40, CCL21, PRKCB, PLCG2
|
miR-6515-5p |
CSNK2A2
| |
miR-663b |
TNFRSF11A
|
PLCG1, |
miR-92a-3p |
CSNK2A2, TRAF5, PLCG1, TRFRSF11A, BCL2L1
| |
miR-934 |
TNFRSF11A
|
PLAU
|