Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Treatment Strategy
2.3. β-Catenin Immunostaining
2.4. Statistical Analysis
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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β-Catenin Low | β-Catenin High | p | |
---|---|---|---|
n = 25 | n = 35 | ||
Age, mean (SD) | 67.52 (9.91) | 64.37 (8.30) | 0.187 |
<65, n (%) | 9 (36.0) | 16 (45.7) | 0.596 |
>65, n (%) | 16 (64.0) | 19 (54.3) | |
<70 | 15 (60.0) | 25 (71.4) | 0.412 |
>70 | 10 (40.0) | 10 (28.6) | |
Sex, n (%) | |||
Male | 19 (76.0) | 24 (68.6) | 0.575 |
Female | 6 (24.0) | 11 (31.4) | |
BMI (kg/m2) † | 23.22 (17.8–30.6) | 19.47 (15.8–30.7) | 0.026 |
ASA-PS score, n (%) | 0.936 | ||
1 | 12 (48.0) | 18 (51.4) | |
2 | 10 (40.0) | 12 (34.3) | |
3 | 3 (12.0) | 5 (14.3) | |
cT *, n (%) | |||
0, 1 | 1 (4.0) | 0 (0.0) | 0.004 |
2 | 4 (16.0) | 0 (0.0) | |
3 | 13 (52.0) | 30 (85.7) | |
4 | 7 (28.0) | 5 (14.3) | |
cN *, n (%) | |||
0 | 4 (16.0) | 6 (17.1) | 1.00 |
1 | 8 (32.0) | 11 (31.4) | |
2 | 13 (52.0) | 18 (51.5) | |
cM *, n (%) | |||
0 | 22 (88.0) | 30 (85.7) | 1.00 |
1 | 3 (12.0) | 5 (14.3) | |
cStage *, n (%) | |||
0–I | 0 (0.0) | 0 (0.0) | 1.00 |
II | 4 (16.0) | 6 (17.1) | |
III | 18 (72.0) | 24 (68.6) | |
IV | 3 (12.0) | 5 (14.3) | |
Completion of NACRT | |||
Yes | 22 (88.0) | 34 (97.1) | 0.298 |
No | 3 (12.0) | 1 (2.9) | |
Adjuvant chemotherapy, n (%) | |||
Yes | 16 (64.0) | 17 (36.4) | 0.297 |
No | 9 (36.0) | 18 (63.6) |
β-Catenin Low | β-Catenin High | p Value | |
---|---|---|---|
n = 25 | n = 35 | ||
Operative procedure, n (%) | |||
HAR | 0 (0.0) | 1 (2.9) | 0.958 |
LAR | 7 (28.0) | 10 (28.6) | |
ISR | 2 (8.0) | 4 (11.4) | |
APR | 16 (64.0) | 20 (57.1) | |
Hartmann | 0 (0.0) | 0 (0.0) | |
Surgical approach, n (%) | |||
Open | 7 (28.0) | 13 (37.1) | 0.581 |
Laparoscopy | 18 (72.0) | 22 (62.9) | |
D, n (%) | |||
D1 | 0 (0.0) | 0 (0.0) | 1.000 |
D2 | 2 (8.0) | 3 (8.6) | |
D3 | 23 (92.0) | 32 (91.4) | |
LLND, n (%) | |||
Yes | 15 (60.0) | 20 (57.1) | 1.000 |
No | 10 (40.0) | 15 (42.9) | |
Operation time (min) † | 489.24 (211–1052) | 516.83 (244–1138) | 0.609 |
Estimated blood loss (ml) † | 649.36 (0–4200) | 603.91 (0–5345) | 0.861 |
Blood transfusion, n (%) | |||
Yes | 9 (36.0) | 10 (28.6) | 0.583 |
No | 16 (64.0) | 25 (71.4) |
β-Catenin Low | β-Catenin High | p Value | |
---|---|---|---|
n = 25 | n = 35 | ||
Postoperative complications (CD ≥ II), n (%) | |||
wound infection | 2 (8.0) | 3 (5.7) | 1.000 |
wound dehiscence | 0 (0.0) | 0 (0.0) | NA |
anastomotic leakage | 1 (4.0) | 4 (11.4) | 0.390 |
bowel obstruction | 1 (4.0) | 2 (5.7) | 1.000 |
lymphorrhea | 2 (8.0) | 1 (2.9) | 0.565 |
deep vein thrombosis | 0 (0.0) | 0 (0.0) | NA |
dysuria | 2 (8.0) | 4 (11.4) | 1.000 |
ureteric injury | 0 (0.0) | 2 (5.7) | 0.506 |
others | 2 (8.0) | 3 (8.6) | 1.000 |
Postoperative complications (CD ≥ III), n (%) | 7 (28.0) | 10 (28.6) | 1.000 |
Postoperative hospital stay †, days (range) | 41.48 (15–181) | 50.20 (12–205) | 0.406 |
Mortality within 30 days, n (%) | 0 (0.0) | 0 (0.0) | 1.000 |
Reoperation within 30 days, n (%) | 0 (0.0) | 0 (0.0) | 1.000 |
Recurrence, n (%) | |||
Yes | 19 (76.0) | 23 (65.7) | 0.569 |
No | 6 (24.0) | 13 (34.3) |
β-Catenin Low | β-Catenin High | p Value | |
---|---|---|---|
n = 25 | n = 35 | ||
ypT *, n (%) | |||
0-is | 4 (16.0) | 0 (0.0) | 0.019 |
1 | 2 (8.0) | 0 (0.0) | |
2 | 6 (24.0) | 8 (22.9) | |
3 | 13 (52.0) | 25 (71.4) | |
4 | 0 (0.0) | 2 (5.7) | |
ypN *, n (%) | |||
0 | 17 (68.0) | 19 (54.3) | 0.441 |
1 | 5 (20.0) | 8 (22.9) | |
2 | 3 (12.0) | 8 (5.7) | |
ypM *, n (%) | |||
0 | 24 (96.0) | 31 (88.6) | 1.00 |
1 | 1 (4.0) | 4 (11.4) | |
ypStage *, n (%) | |||
0 | 4 (16.0) | 0 (0.0) | 0.0521 |
I | 5 (20.0) | 5 (14.3) | |
II | 8 (32.0) | 14 (40.0) | |
III | 7 (28.0) | 12 (34.3) | |
IV | 1 (4.0) | 4 (8.75) | |
Histological type *, n (%) | 0.508 | ||
Well/moderately | 21 (84.0) | 32 (91.4) | |
Mucinous/poorly | 3 (12.0) | 3 (8.6) | |
Other | 1 (4.0) | 0 (0.0) | |
Vascular invasion, n (%) | |||
Absent | 20 (80.0) | 15 (42.9) | 0.007 |
Present | 5 (20.0) | 20 (57.1) | |
Lymphatic invasion, n (%) | |||
Absent | 20 (80.0) | 25 (71.4) | 0.552 |
Present | 5 (20.0) | 10 (28.6) | |
Histological response ** (%) | |||
Poor (Grade 1a, 1b) | 7 (28.0) | 22 (62.9) | <0.01 |
Good (Grade 2, 3) | 18 (72.0) | 13 (37.1) |
Univariate Analysis | Multivariate Analysis | ||||
---|---|---|---|---|---|
Factor | n | HR | p Value | HR | p Value |
Age (>70/<70) | 20/40 | 0.598 (0.20–1.82) | 0.364 | ||
Sex (male/female) | 42/18 | 2.637 (0.76–9.14) | 0.126 | ||
ASA-PS (>2/1,2) | 8/52 | 1.075 (0.25–4.69) | 0.923 | ||
Postoperative Complication (CD ≥III/CD I, II) | 17/43 | 0.881 (0.29–2.68) | 0.824 | ||
β-catenin staining, nuclear (High/Low) | 35/25 | 1.444 (0.54–3.85) | 0.462 | ||
β-catenin staining, nuclear-cytoplasm (the others/Low-High) | 51/9 | 3.324 (0.44–24.9) | 0.243 | ||
Pathological Response (Poor/Good) | 29/31 | 2.629 (0.96–7.01) | 0.054 | 2.322 (0.81–6.63) | 0.115 |
Surgical Method (open/laparo) | 20/40 | 2.168 (0.86–5.46) | 0.101 | ||
ypT (3,4/0,1,2) | 40/20 | 1.372 (0.49–3.86) | 0.548 | ||
ypN (positive/negative) | 24/36 | 3.276 (1.27–8.47) | 0.014 | 2.524 (0.95–6.69) | 0.062 |
Ly (present/absent) | 15/45 | 2.354 (0.91–6.11) | 0.078 | 1.941 (0.69–5.42) | 0.205 |
V (present/absent) | 25/35 | 2.804 (1.08–7.27) | 0.034 | 1.440 (0.48–4.32) | 0.515 |
Histology (por, muc/tub1, 2) | 7/53 | 1.561 (0.45–5.40) | 0.482 | ||
Adjuvant chemotherapy (No/Yes) | 27/33 | 1.313 (0.52–3.33) | 0.566 |
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Miyako, S.; Matsuda, T.; Koma, Y.-i.; Koide, T.; Sawada, R.; Hasegawa, H.; Yamashita, K.; Harada, H.; Urakawa, N.; Goto, H.; et al. Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer. Biomedicines 2023, 11, 174. https://doi.org/10.3390/biomedicines11010174
Miyako S, Matsuda T, Koma Y-i, Koide T, Sawada R, Hasegawa H, Yamashita K, Harada H, Urakawa N, Goto H, et al. Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer. Biomedicines. 2023; 11(1):174. https://doi.org/10.3390/biomedicines11010174
Chicago/Turabian StyleMiyako, Shoji, Takeru Matsuda, Yu-ichiro Koma, Takahiro Koide, Ryuichiro Sawada, Hiroshi Hasegawa, Kimihiro Yamashita, Hitoshi Harada, Naoki Urakawa, Hironobu Goto, and et al. 2023. "Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer" Biomedicines 11, no. 1: 174. https://doi.org/10.3390/biomedicines11010174
APA StyleMiyako, S., Matsuda, T., Koma, Y.-i., Koide, T., Sawada, R., Hasegawa, H., Yamashita, K., Harada, H., Urakawa, N., Goto, H., Kanaji, S., Oshikiri, T., & Kakeji, Y. (2023). Significance of Wnt/β-Catenin Signal Activation for Resistance to Neoadjuvant Chemoradiotherapy in Rectal Cancer. Biomedicines, 11(1), 174. https://doi.org/10.3390/biomedicines11010174