CDX2-Suppressed Colorectal Cancers Possess Potentially Targetable Alterations in Receptor Tyrosine Kinases and Other Colorectal-Cancer-Associated Pathways
Abstract
:1. Introduction
2. Methods
3. Results
3.1. The TCGA Colorectal Cancer Cohort
3.2. The Sidra-LUMC AC-ICAM Cohort
4. Discussion
5. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristic | Entire Cohort (n = 594) | CDX2 Suppressed (n = 75) | Non CDX2 Suppressed (n = 249) | p |
---|---|---|---|---|
Age (mean +/− SD) | 66.1 +/− 13.4 | 64.4 +/− 15.3 | 66.6 +/− 12.5 | 0.2 |
Age | ||||
≤65 years-old | 260 (43.9) | 36 (48) | 106 (42.7) | 0. 42 |
>65 years-old | 332 (56.1) | 39 (52) | 142 (57.3) | |
NA | 2 | 1 | ||
Sex | ||||
Male | 312 (52.7) | 36 (48) | 139 (56) | 0. 23 |
Female | 280 (47.3) | 39 (52) | 109 (44) | |
NA | 2 | 1 | ||
stage | ||||
I | 104 (17.9) | 7 (9.6) | 40 (16.4) | I–II versus III–IV |
II | 220 (37.9) | 36 (49.3) | 90 (36.9) | 0.35 |
III | 170 (29.3) | 22 (30.1) | 74 (30.3) | |
IV | 86 (14.8) | 8 (11) | 40 (16.4) | |
NA | 14 | 2 | 5 | |
Location primary | ||||
Colon | 436 (74.1) | 66 (88) | 174 (69.9) | 0.001 |
Rectal | 152 (25.9) | 9 (12) | 75 (30.1) | |
NA | 6 |
Characteristic | Entire Cohort (n = 594) | CDX2 Suppressed (n = 75) | Non CDX2 Suppressed (n = 249) | p |
---|---|---|---|---|
Subtype | ||||
GS | 58 (12.7) | 3 (4.9) | 20 (10) | GS versus CIN versus MSI |
CIN | 328 (71.4) | 23 (37.8) | 176 (88) | <0.0001 |
MSI | 63 (13.7) | 33 (54.1) | 3 (1.5) | |
POLE | 10 (2.2) | 2 (3.2) | 1 (0.5) | |
NA | 135 | 14 | 49 | |
TMB | ||||
≤10 | 451 | 30 (46.2) | 219 (96.5) | <0.0001 |
>10 | 83 | 35 (53.8) | 8 (3.5) | |
NA | 60 | 10 | 22 | |
AS | ||||
<4 | 108 (18.4) | 34 (45.9) | 16 (6.5) | <0.0001 |
4–24 | 427 (72.9) | 36 (48.7) | 211 (85.1) | |
>24 | 51 (8.7) | 4 (5.4) | 21 (8.4) | |
NA | 8 | 1 | 1 | |
FGA | ||||
<0.08 | 118 (20.2) | 19 (25.3) | 15 (6.1) | <0.0001 |
0.08–0.35 | 316 (54.2) | 44 (58.7) | 77 (31.6) | |
>0.35 | 149 (25.6) | 12 (16) | 152 (62.3) | |
NA | 11 | 5 |
Gene | Entire Cohort (n = 594) (%) | Putative Drivers (%) | CDX2 Suppressed (n = 75) (%) | Putative Drivers (%) | p |
---|---|---|---|---|---|
EGFR | 19 (3.2) | 3 (0.5) | 10 (13.3) | 3 (4) | 0.34 |
ERBB3 | 32 (5.4) | 14 (2.4) | 10 (13.3) | 4 (5.3) | 1 |
ERBB4 | 62 (10.4) | 4 (0.7) | 13 (17.3) | 1 (1.3) | 1 |
FGFR2 | 22 (3.7) | 2 (0.3) | 11 (14.7) | 1 (1.3) | 1 |
FGFR3 | 18 (3) | 1 (0.2) | 6 (8) | 0 | 1 |
RET | 30 (5.1) | 2 (0.3) | 12 (16) | 2 (2.7) | 0.56 |
ALK | 41 (6.9) | 1 (0.2) | 14 (18.7) | 0 | 1 |
NTRK3 | 29 (4.9) | 3 (0.5) | 9 (12) | 1 (1.3) | 1 |
BRAF | 67 (11.3) | 56 (9.4) | 33 (44) | 30 (40) | 0.37 |
NF1 | 43 (7.2) | 18 (3) | 15 (20) | 6 (8) | 1 |
RASA1 | 29 (4.9) | 8 (1.3) | 10 (13.3) | 1 (1.3) | 0.39 |
PIK3CB | 16 (2.7) | 2 (0.3) | 3 (4) | 0 | 1 |
PIK3R1 | 38 (6.4) | 29 (4.9) | 11 (14.7) | 9 (12) | 1 |
PTEN | 48 (8.1) | 46 (7.7) | 15 (20) | 15 (20) | 1 |
PPP2R1A | 15 (2.5) | 6 (1) | 6 (8) | 2 (2.7) | 1 |
TSC1 | 21 (3.5) | 7 (1.2) | 11 (14.7) | 6 (8) | 0.28 |
MTOR | 46 (7.7) | 5 (0.8) | 14 (18.7) | 0 | 0.32 |
MSH2 | 27 (4.5) | 10 (1.7) | 7 (9.3) | 4 (5.3) | 0.41 |
MSH6 | 29 (4.9) | 8 (1.3) | 8 (10.7) | 2 (2.7) | 1 |
PMS2 | 16 (2.7) | 4 (0.7) | 6 (8) | 1 (1.3) | 1 |
MLH1 | 24 (4) | 13 (2.2) | 9 (12) | 2 (2.7) | 0.13 |
POLE | 50 (8.4) | 11 (1.9) | 17 (22.7) | 2 (2.7) | 0.48 |
BRCA1 | 19 (3.2) | 5 (0.8) | 5 (6.7) | 2 (2.7) | 0.6 |
BRCA2 | 69 (11.6) | 18 (3) | 21 (28) | 8 (10.7) | 0.28 |
ATM | 107 (18) | 52(8.8) | 34 (45.3) | 16 (21.3) | 1 |
BRIP1 | 25 (4.2) | 4 (0.7) | 7 (9.3) | 1 (1.3) | 1 |
CDK12 | 42 (7.1) | 15 (2.5) | 10 (13.3) | 7 (9.3) | 0.07 |
RNF43 | 58 (9.8) | 38 (6.4) | 24 (32) | 15 (20) | 0.8 |
LRP1B | 190 (32) | 44 (7.4) | 43 (57.3) | 13 (17.3) | 0.33 |
AMER1 | 72 (12.1) | 52 (8.8) | 12 (16) | 8 (10.7) | 0.73 |
AXIN2 | 36 (6.1) | 22 (3.7) | 14 (18.7) | 10 (13.3) | 0.74 |
FAT1 | 99 (16.7) | 15 (2.5) | 35 (46.7) | 4 (5.3) | 0.77 |
Characteristic | Entire Cohort (n = 348) | CDX2 Suppressed (n = 21) | Non CDX2 Suppressed (n = 219) | p |
---|---|---|---|---|
Age | ||||
Mean (±SD) | 68.2 ± 11.5 | 72.3 ± 9.5 | 68.4 ± 10.7 | 0.1 |
>65 years old | 233 (67) | 15 (71.4) | 151 (68.9) | 1 |
≤65 years old | 115 (33) | 6 (28.6) | 68 (31.1) | |
Gender | ||||
Male | 182 (52.3) | 5 (23.8) | 123 (56.2) | 0.005 |
Female | 166 (47.7) | 16 (76.2) | 96 (43.8) | |
Stage | ||||
I | 55 (15.8) | 0 | 46 (21) | |
II | 122 (35.1) | 8 (38.1) | 69 (31.5) | 1 (Stage I–III versus IV) |
III | 110 (31.6) | 9 (42.9) | 65 (29.7) | |
IV | 61 (17.5) | 4 (19) | 39 (17.8) | |
Primary location | ||||
Cecum-ascending colon–hepatic flexure | 158 (45.4) | 17 (81) | 95 (43.4) | 0.001 |
Transverse colon–splenic flexure-descending colon–sigmoid | 190 (54.6) | 4 (19) | 124 (56.6) | |
Consensus Mol Subtype | ||||
CMS1 | 43 (12.4) | 14 (66.7) | 5 (2.3) | <0.0001 |
CMS2 | 76 (21.8) | 0 | 74 (33.8) | |
CMS3 | 66 (19) | 0 | 52 (23.7) | |
CMS4 | 82 (23.6) | 6 (28.6) | 40 (18.3) | |
Mixed | 81 (23.3) | 1 (4.8) | 48 (21.9) | |
FGA | ||||
≤0.08 | 88 (31.3) | 11(68.8) | 38 (21) | 0.0001 |
>0.08 | 193 (68.7) | 5 (31.2) | 143 (79) | |
NA | 67 | 5 | 38 | |
TMB | ||||
≤10 mutations/Mb | 208 (74) | 3 (18.7) | 160 (88.4) | 0.0001 |
>10 mutations/Mb | 73 (26) | 13 (81.3) | 21 (11.6) | |
NA | 67 | 5 | 38 |
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Voutsadakis, I.A. CDX2-Suppressed Colorectal Cancers Possess Potentially Targetable Alterations in Receptor Tyrosine Kinases and Other Colorectal-Cancer-Associated Pathways. Diseases 2024, 12, 234. https://doi.org/10.3390/diseases12100234
Voutsadakis IA. CDX2-Suppressed Colorectal Cancers Possess Potentially Targetable Alterations in Receptor Tyrosine Kinases and Other Colorectal-Cancer-Associated Pathways. Diseases. 2024; 12(10):234. https://doi.org/10.3390/diseases12100234
Chicago/Turabian StyleVoutsadakis, Ioannis A. 2024. "CDX2-Suppressed Colorectal Cancers Possess Potentially Targetable Alterations in Receptor Tyrosine Kinases and Other Colorectal-Cancer-Associated Pathways" Diseases 12, no. 10: 234. https://doi.org/10.3390/diseases12100234
APA StyleVoutsadakis, I. A. (2024). CDX2-Suppressed Colorectal Cancers Possess Potentially Targetable Alterations in Receptor Tyrosine Kinases and Other Colorectal-Cancer-Associated Pathways. Diseases, 12(10), 234. https://doi.org/10.3390/diseases12100234