Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Immune-Related and Inflammatory Markers in the Tumor Tissues
2.3. Relationships between Immune-Related and Inflammatory Markers and Clinicopathologic Features
2.4. Relationships between Immune-Related and Inflammatory Markers and Long-Term Oncologic Outcomes
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Tissue Sample Preparation
4.3. Selection of Immune-Related and Inflammatory Markers
4.4. Bio-Plex Multiplex Immunoassay System
4.5. Surgery and Pathological Examination
4.6. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Number of Patients (n = 70) | Percentage (%) | |
---|---|---|
Age, mean ± SD | 69.6 ± 10.8 | |
Gender | ||
Male | 38 | 54.3 |
Female | 32 | 45.7 |
Body mass index, mean ± SD | 23.4 ± 3.5 | |
ASA score | ||
II | 35 | 50.0 |
III | 35 | 50.0 |
Medical history | ||
None | 19 | 27.1 |
One | 18 | 25.7 |
Two or more | 33 | 47.1 |
Tumor location | ||
Right | 19 | 27.1 |
Left | 27 | 38.6 |
Rectum | 24 | 34.3 |
CEA | ||
<5 | 45 | 64.3 |
≥5 | 25 | 35.7 |
Operation method | ||
Open | 15 | 21.4 |
MIS | 55 | 78.6 |
T stage | ||
Tis | 1 | 1.4 |
3 | 53 | 75.7 |
4 | 16 | 22.9 |
N stage | ||
0 | 28 | 40.0 |
1 | 28 | 40.0 |
2 | 14 | 20.0 |
M stage | ||
0 | 57 | 81.4 |
1 | 13 | 18.6 |
TNM stage | ||
0 | 1 | 1.4 |
2 | 25 | 35.7 |
3 | 31 | 44.3 |
4 | 13 | 18.6 |
Metastatic lymph node, mean ± SD | 2.2 ± 3.6 | |
Harvested lymph node, mean ± SD | 24.8 ± 11.1 | |
Tumor differentiation | ||
Good differentiation | 13 | 18.8 |
Moderate differentiation | 53 | 76.8 |
Poor differentiation | 1 | 1.4 |
Mucinous adenocarcinoma | 2 | 2.9 |
Tumor size (cm), mean ± SD | 5.0 ± 2.0 | |
Lymphatic invasion | ||
Negative | 38 | 54.3 |
Positive | 32 | 45.7 |
Venous invasion | ||
Negative | 63 | 90.0 |
Positive | 7 | 10.0 |
Perineural invasion | ||
Negative | 50 | 71.4 |
Positive | 20 | 28.6 |
EGFR | ||
Negative | 5 | 7.6 |
Positive | 61 | 92.4 |
MSI | ||
MSS | 63 | 94.0 |
MSI-H | 4 | 6.0 |
KRAS | ||
Wild | 39 | 58.2 |
Mutant | 28) | 41.8 |
NRAS | ||
Wild | 47 | 92.2 |
Mutant | 2 | 3.9 |
BRAF | ||
Wild | 62 | 95.4 |
Mutant | 3 | 4.6 |
Laboratory markers, mean ± SD | ||
WBC (103/μL) | 7.6 ± 3.1 | |
Hb (g/dL) | 11.9 ± 2.4 | |
PLT (103/μL) | 288.0 ± 100.3 | |
Neutrophil count (103/μL) | 5.4 ± 3.0 | |
Lymphocyte count (103/μL) | 1.5 ± 0.6 | |
NLR | 4.5 ± 4.9 | |
C-reactive protein (mg/dL) | 1.7 ± 2.7 | |
Albumin (g/dL) | 3.8 ± 0.6 | |
Chemotherapy | ||
No | 24 | 34.3 |
Yes | 46 | 65.7 |
Radiotherapy | ||
No | 69 | 98.6 |
Yes | 1 | 1.4 |
Recurrence | ||
No | 42 | 60.0 |
Yes | 17 | 24.3 |
Death | ||
No | 45 | 64.3 |
Yes | 5 | 7.1 |
Median (IQR) | Range | |
---|---|---|
APRIL/TNFSF13 | 166.02 (0, 806.4) | 0~8954.58 |
BAFF | 485.6 (355.3, 664.0) | 0~2053.2 |
CHIT | 21.3 (10.24, 31.24) | 0~101.19 |
MMP-3 | 905.1 (736.2, 1106.9) | 270.5~5198.8 |
Osteocalcin | 16.33 (2.37, 41.34) | 0~487.48 |
Pentraxin-3 | 8.98 (7.41, 12.19) | 3.23~57.43 |
sTNF-R1 | 6.67 (5.43, 7.87) | 2.28~36.20 |
sTNF-R2 | 60.99 (35.78, 106.93) | 0~177.87 |
LAG-3 | 0 (0, 11.46) | 0~164.96 |
PD-1 | 5.3 (5.30, 10.84) | 0~21.77 |
PD-L1 | 0 (0, 0.43) | 0~4.49 |
CTLA-4 | 0 (0, 0) | 0~3.1 |
APRIL/TNFSF13 (806.4) | p | BAFF (664.0) | p | MMP-3 (736.2) | p | ||||
---|---|---|---|---|---|---|---|---|---|
Low (N = 51) | High (N = 19) | Low (N = 52) | High (N = 18) | Low (N = 23) | High (N = 47) | ||||
Age, mean ± SD | 69.8 ± 10.7 | 69.2 ± 11.0 | 0.82 | 69.4 ± 11.1 | 70.3 ± 10.1 | 0.74 | 70.7 ± 11.4 | 69.1 ± 10.5 | 0.59 |
Gender | |||||||||
Male | 27 (52.9) | 11 (57.9) | 0.92 | 25 (48.1) | 13 (72.2) | 0.13 | 15 (65.2) | 23 (48.9) | 0.30 |
Female | 24 (47.1) | 8 (42.1) | 27 (51.9) | 5 (27.8) | 8 (34.8) | 24 (51.1) | |||
BMI | 23.5 ± 3.7 | 23.1 ± 3.1 | 0.70 | 23.4 ± 3.7 | 23.4 ± 3.0 | 0.96 | 23.3 ± 3.6 | 23.4 ± 3.5 | 0.90 |
ASA score | |||||||||
II | 28 (54.9) | 7 (36.8) | 0.28 | 29 (55.8) | 6 (33.3) | 0.17 | 13 (56.5) | 22 (46.8) | 0.61 |
III | 23 (45.1) | 12 (63.2) | 23 (44.2) | 12 (66.7) | 10 (43.5) | 25 (53.2) | |||
Medical history | |||||||||
None | 14 (27.5) | 5 (26.3) | 0.95 * | 12 (23.1) | 7 (38.9) | 0.22 * | 6 (26.1) | 13 (27.7) | 0.81 |
One | 14 (27.5) | 4 (21.1) | 16 (30.8) | 2 (11.1) | 5 (21.7) | 13 (27.7) | |||
T or more | 23 (45.1) | 10 (52.6) | 24 (46.2) | 9 (50.0) | 12 (52.2) | 21 (44.7) | |||
Tumor location | |||||||||
Right | 15 (29.4) | 4 (21.1) | 0.65 | 17 (32.7) | 2 (11.1) | 0.13 * | 8 (34.8) | 11 (23.4) | 0.51 |
Left | 20 (39.2) | 7 (36.8) | 20 (38.5) | 7 (38.9) | 7 (30.4) | 20 (42.6) | |||
Rectum | 16 (31.4) | 8 (42.1) | 15 (28.8) | 9 (50.0) | 8 (34.8) | 16 (34.0) | |||
CEA | |||||||||
<5 | 34 (66.7) | 11 (57.9) | 0.68 | 34 (65.4) | 11 (61.1) | 0.96 | 19 (82.6) | 26 (55.3) | 0.04 |
≥5 | 17 (33.3) | 8 (42.1) | 18 (34.6) | 7 (38.9) | 4 (17.4) | 21 (44.7) | |||
Operation method | |||||||||
Open | 10 (19.6) | 5 (26.3) | 0.53 * | 11 (21.2) | 4 (22.2) | 1 * | 6 (26.1) | 9 (19.1) | 0.54 * |
MIS | 41 (80.4) | 14 (73.7) | 41 (78.8) | 14 (77.8) | 17 (73.9) | 38 (80.9) | |||
T stage | |||||||||
Tis | 0 (0.0) | 1 (5.3) | 0.29 * | 0 (0.0) | 1 (5.6) | 0.09 * | 0 (0.0) | 1 (2.1) | 0.01 * |
3 | 40 (78.4) | 13 (68.4) | 42 (80.8) | 11 (61.1) | 22 (95.7) | 31 (66.0) | |||
4 | 11 (21.6) | 5 (26.3) | 10 (19.2) | 6 (33.3) | 1 (4.3) | 15 (31.9) | |||
N stage | |||||||||
0 | 22 (43.1) | 6 (31.6) | 0.60 * | 20 (38.5) | 8 (44.4) | 0.81 * | 13 (56.5) | 15 (31.9) | 0.15 * |
1 | 20 (39.2) | 8 (42.1) | 22 (42.3) | 6 (33.3) | 6 (26.1) | 22 (46.8) | |||
2 | 9 (17.6) | 5 (26.3) | 10 (19.2) | 4 (22.2) | 4 (17.4) | 10 (21.3) | |||
M stage | |||||||||
0 | 45 (88.2) | 12 (63.2) | 0.03 * | 45 (86.5) | 12 (66.7) | 0.08 * | 21 (91.3) | 36 (76.6) | 0.19 * |
1 | 6 (11.8) | 7 (36.8) | 7 (13.5) | 6 (33.3) | 2 (8.7) | 11 (23.4) | |||
TNM stage | |||||||||
0 | 0 (0.0) | 1 (5.3) | 0.02 * | 0 (0.0) | 1 (5.6) | 0.06 * | 0 (0.0) | 1 (2.1) | 0.04 * |
2 | 21 (41.2) | 4 (21.1) | 19 (36.5) | 6 (33.3) | 13 (56.5) | 12 (25.5) | |||
3 | 24 (47.1) | 7 (36.8) | 26 (50.0) | 5 (27.8) | 8 (34.8) | 23 (48.9) | |||
4 | 6 (11.8) | 7 (36.8) | 7 (13.5) | 6 (33.3) | 2 (8.7) | 11 (23.4) | |||
Metastatic lymph node | 1.8 ± 3.3 | 3.2 ± 4.3 | 0.23 | 2.0 ± 3.3 | 2.8 ± 4.4 | 0.45 | 1.1 ± 1.7 | 2.7 ± 4.2 | 0.02 |
Harvested lymph node | 24.4 ± 9.4 | 25.9 ± 14.9 | 0.68 | 25.3 ± 9.8 | 23.4 ± 14.4 | 0.62 | 27.1 ± 13.1 | 23.7 ± 9.9 | 0.27 |
Tumor differentiation | |||||||||
WD | 10 (19.6) | 3 (16.7) | 0.79 * | 9 (17.3) | 4 (23.5) | 0.63 * | 4 (17.4) | 9 (19.6) | 0.91 * |
MD | 39 (76.5) | 14 (77.8) | 41 (78.8) | 12 (70.6) | 19 (82.6) | 34 (73.9) | |||
PD | 1 (2.0) | 0 (0.0) | 1 (1.9) | 0 (0.0) | 0 (0.0) | 1 (2.2) | |||
Mucinous | 1 (2.0) | 1 (5.6) | 1 (1.9) | 1 (5.9) | 0 (0.0) | 2 (4.3) | |||
Tumor size (cm), mean ± SD | 4.9 ± 2.2 | 5.2 ± 1.3 | 0.50 | 4.9 ± 2.2 | 5.1 ± 1.5 | 0.64 | 4.8 ± 2.0 | 5.0 ± 2.1 | 0.74 |
Lymphatic invasion | |||||||||
Negative | 28 (54.9) | 10 (52.6) | 1 | 28 (53.8) | 10 (55.6) | 1 | 11 (47.8) | 27 (57.4) | 0.61 |
Positive | 23 (45.1) | 9 (47.4) | 24 (46.2) | 8 (44.4) | 12 (52.2) | 20 (42.6) | |||
Venous invasion | |||||||||
Negative | 47 (92.2) | 16 (84.2) | 0.37 * | 47 (90.4) | 16 (88.9) | 1 * | 21 (91.3) | 42 (89.4) | 1 * |
Positive | 4 (7.8) | 3 (15.8) | 5 (9.6) | 2 (11.1) | 2 (8.7) | 5 (10.6) | |||
Perineural invasion | |||||||||
Negative | 40 (78.4) | 10 (52.6) | 0.06 | 40 (76.9) | 10 (55.6) | 0.15 | 19 (82.6) | 31 (66.0) | 0.24 |
Positive | 11 (21.6) | 9 (47.4) | 12 (23.1) | 8 (44.4) | 4 (17.4) | 16 (34.0) | |||
EGFR | |||||||||
Negative | 1 (2.1) | 4 (22.2) | 0.01 * | 1 (2.0) | 4 (25.0) | 0.01 * | 0 (0.0) | 5 (11.6) | 0.15 * |
Positive | 47 (97.9) | 14 (77.8) | 49 (98.0) | 12 (75.0) | 23 (100.0) | 38 (88.4) | |||
MSI | |||||||||
MSS | 46 (92.0) | 17 (100.0) | 0.56 * | 47 (92.2) | 16 (100.0) | 0.56 * | 21 (91.3) | 42 (95.5) | 0.60 * |
MSI-H | 4 (8.0) | 0 (0.0) | 4 (7.8) | 0 (0.0) | 2 (8.7) | 2 (4.5) | |||
KRAS | |||||||||
Wild | 27 (56.2) | 12 (63.2) | 0.80 | 29 (59.2) | 10 (55.6) | 1 | 12 (57.1) | 27 (58.7) | 1 |
Mutant | 21 (43.8) | 7 (36.8) | 20 (40.8) | 8 (44.4) | 9 (42.9) | 19 (41.3) | |||
NRAS | |||||||||
Wild | 33 (97.1) | 14 (93.3) | 0.52 * | 35 (97.2) | 12 (92.3) | 0.46 * | 16 (100.0) | 31 (93.9) | 1 * |
Mutant | 1 (2.9) | 1 (6.7) | 1 (2.8) | 1 (7.7) | 0 (0.0) | 2 (6.1) | |||
BRAF | |||||||||
Wild | 45 (95.7) | 17 (94.4) | 1 * | 45 (93.8) | 17 (100.0) | 0.56 * | 19 (95.0) | 43 (95.6) | 1 * |
Mutant | 2 (4.3) | 1 (5.6) | 3 (6.2) | 0 (0.0) | 1 (5.0) | 2 (4.4) | |||
Laboratory markers, median [IQR] | |||||||||
WBC (103/μL) | 6.6(5.4, 9.2) | 7.1 (6.5, 8.8) | 0.53 | 7.2 (5.5, 9.2) | 6.7 (5.9, 8.9) | 0.83 | 6.5 (4.9, 7.6) | 7.2 (5.9, 9.4) | 0.10 |
Hb (g/dL) | 12.6 (10.4, 13.6) | 11.1 (9.7, 12.5) | 0.13 | 12.4 (10.2, 13.4) | 12.4 (9.8, 13.8) | 0.87 | 12.4 (10.1, 13.8) | 12.3 (10.2, 13.6) | 0.58 |
PLT (103/μL) | 272.0 (209.5, 323.0) | 253.0 (231.0, 331.0) | 0.92 | 275.5 (212.2, 333.5) | 242.0 (224.5, 294.2) | 0.37 | 260.0 (193.0, 307.0) | 259.0 (222.5, 332.5) | 0.42 |
Neutrophil (103/μL) | 4.7 (3.0, 6.4) | 5.1 (4.4, 7.1) | 0.17 | 4.7 (3.1, 6.9) | 4.9 (4.3, 6.8) | 0.38 | 3.6 (3.0, 5.8) | 4.9 (3.7, 7.1) | 0.08 |
Lymphocyte (103/μL) | 1.6 (1.3, 1.9) | 1.3 (1.0, 1.8) | 0.20 | 1.5 (1.2, 1.9) | 1.3 (1.0, 1.8) | 0.49 | 1.4 (1.2, 1.7) | 1.6 (1.1, 1.9) | 0.48 |
NLR | 2.7 (2.1, 4.2) | 4.1 (2.7, 6.0) | 0.04 | 2.7 (2.2, 4.4) | 3.9 (2.7, 5.4) | 0.15 | 2.5 (2.1, 4.1) | 3.6 (.5, 5.2) | 0.16 |
CRP (mg/dL) | 0.4 (0.3, 1.6) | 1.0 (0.3, 2.3) | 0.25 | 0.5 (0.3, 1.8) | 0.7 (0.3, 1.3) | 0.97 | 0.6 (0.3, 1.3) | 0.7 (0.3, 1.8) | 0.99 |
Albumin (g/dL) | 3.9 (3.6, 4.3) | 3.7 (3.2, 4.0) | 0.07 | 3.9 (3.6, 4.2) | 3.8 (3.3, 4.2) | 0.58 | 3.8 (3.2, 4.2) | 3.9 (3.5, 4.3 | 0.31 |
Chemotherapy | |||||||||
No | 17 (33.3) | 7 (36.8) | 1 | 16 (30.8) | 8 (44.4) | 0.44 | 9 (39.1) | 15 (31.9) | 0.74 |
Yes | 34 (66.7) | 12 (63.2) | 36 (69.2) | 10 (55.6) | 14 (60.9) | 32 (68.1) | |||
Radiotherapy | |||||||||
No | 50 (98.0) | 19 (100.0) | 1 * | 51 (98.1) | 18 (100.0) | 1 * | 22 (95.7) | 47 (100.0) | 0.32 * |
Yes | 1 (2.0) | 0 (0.0) | 1 (1.9) | 0 (0.0) | 1 (4.3) | 0 (0.0) | |||
Recurrence | |||||||||
No | 34 (66.7) | 8 (42.1) | 0.06 * | 35 (67.3) | 7 (38.9) | 0.03 * | 16 (69.6) | 26 (55.3) | 0.08 * |
Yes | 12 (23.5) | 5 (26.3) | 12 (23.1) | 5 (27.8) | 2 (8.7) | 15 (31.9) | |||
Death | |||||||||
No | 36 (70.6) | 9 (47.4) | 0.11 * | 37 (71.2) | 8 (44.4) | 0.08 * | 16 (69.6) | 29 (61.7) | 0.78 * |
Yes | 4 (7.8) | 1 (5.3) | 3 (5.8) | 2 (11.1) | 1 (4.3) | 4 (8.5) |
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An, S.; Kim, S.-K.; Kwon, H.Y.; Kim, C.S.; Bang, H.-J.; Do, H.; Kim, B.; Kim, K.; Kim, Y. Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients. Int. J. Mol. Sci. 2023, 24, 11579. https://doi.org/10.3390/ijms241411579
An S, Kim S-K, Kwon HY, Kim CS, Bang H-J, Do H, Kim B, Kim K, Kim Y. Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients. International Journal of Molecular Sciences. 2023; 24(14):11579. https://doi.org/10.3390/ijms241411579
Chicago/Turabian StyleAn, Sanghyun, Soo-Ki Kim, Hye Youn Kwon, Cheol Su Kim, Hui-Jae Bang, Hyejin Do, BoRa Kim, Kwangmin Kim, and Youngwan Kim. 2023. "Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients" International Journal of Molecular Sciences 24, no. 14: 11579. https://doi.org/10.3390/ijms241411579