Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer
Abstract
:1. Introduction
2. Results
2.1. Immunohistochemical POSTN Expression in NSCLC
2.2. Relationship between Immunohistochemical POSTN Expression in NSCLC and the Clinicopathological Data of Patients
2.3. Associations between POSTN and TTF-1, p63, and D2-40 Expression Levels and Cancer Cell Proliferation
2.4. Prognostic Significance of POSTN Expression in NSCLC
2.5. Immunofluorescence
2.6. Laser Capture Microdissection and Real-Time PCR
3. Discussion
4. Materials and Methods
4.1. Patient Cohort
4.2. Construction of Tissue Microarrays (TMA)
4.3. TMA Immunohistochemistry (IHC)
4.4. Evaluation of IHC Reactions
4.5. Laser Capture Microdissection (LCM)
4.6. Real-Time PCR
4.7. Confocal Microscopy
4.8. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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A | ||||||||
Overall Survival (OS) | ||||||||
Clinicopathological Parameters | NSCLC | |||||||
Univariate Analysis | Multivariate Analysis | |||||||
p-Value | HR (95% HR CI) | p-Value | HR (95% HR CI) | |||||
Age (<62 vs. >62) | 0.0002 | 1.39 (1.17–1.66) | 0.0001 | 1.41 (1.18–1.69) | ||||
POSTN CAFs (low vs. high) | <0.0001 | 1.15 (1.12–1.18) | <0.0001 | 1.12 (1.09–1.15) | ||||
Ki-67 (median) | 0.11 | 1.15 (0.97–1.37) | - | - | ||||
Chronic obstructive pulmonary disease | 0.08 | 1.17 (0.98–1.39) | - | - | ||||
Hypertension | 0.57 | 1.05 (0.88–1.25) | - | - | ||||
Coronary artery disease | 0.02 | 1.60 (1.07–2.39) | 0.02 | 1.64 (1.09–2.45) | ||||
Smoking history | 0.29 | 1.01 (0.99–1.03) | - | - | ||||
Stage (I vs. II-IV) | <0.0001 | 2.21 (1.84–2.64) | 0.01 | 1.42 (1.10–1.84) | ||||
Grade (G1 vs. G2-G3) | 0.49 | 0.88 (0.61–1.27) | - | - | ||||
Tumour size (T1–T2 vs. T3–T4) | <0.0001 | 1.92 (1.60–2.29) | 0.0008 | 1.44 (1.16–1.79) | ||||
Lymph nodes involvement (N0 vs. N+) | <0.0001 | 1.84 (1.54–2.19) | 0.0005 | 1.48 (1.19–1.85) | ||||
pM | 0.12 | 1.89 (0.84–4.23) | - | - | ||||
B | ||||||||
Overall Survival (OS) | ||||||||
Clinicopathological Parameters | SCC | AC | ||||||
Univariate Analysis | Multivariate Analysis | Univariate Analysis | Multivariate Analysis | |||||
p-Value | HR (95% HR CI) | p-Value | HR (95% HR CI) | p-Value | HR (95% HR CI) | p-Value | HR (95% HR CI) | |
Age (<62 vs. >62) | 0.05 | 1.32 (1.01–1.73) | 0.03 | 1.35 (1.02–1.79) | 0.03 | 1.36 (1.03–1.79) | 0.003 | 1.53 (1.15–2.02) |
POSTN CAFs (low vs. high) | 0.0007 | 1.62 (1.23–2.14) | 0.001 | 1.58 (1.20–3.28) | <0.0001 | 1.22 (1.16–1.27) | <0.0001 | 1.21 (1.15–1.27) |
Ki-67 (median) | 0.53 | 0.92 (0.70–1.20) | - | - | 0.04 | 1.37 (1.02–1.83) | 0.21 | - |
Chronic obstructive pulmonary disease | 0.44 | 1.11 (0.85–1.46) | - | - | 0.23 | 1.18 (0.90–1.56) | - | - |
Hypertension | 0.73 | 1.05 (0.81–1.37) | - | - | 0.33 | 0.87 (0.66–1.15) | - | - |
Coronary artery disease | 0.73 | 1.05 (0.81–1.37) | - | - | 0.13 | 1.88 (0.83–4.24) | - | - |
Smoking history | 0.37 | 1.01 (0.99–1.03) | - | - | 0.03 | 1.52 (1.04–2.23) | 0.12 | 1.36 (0.92–2.01) |
Stage (I vs. II-IV) | <0.0001 | 1.83 (1.38–2.44) | 0.13 | 1.38 (0.91–2.09) | <0.0001 | 2.44 (1.84–3.23) | 0.43 | 1.18 (0.78–1.78) |
Grade (G1 vs. G2-G3) | 0.31 | 1.48 (0.70–3.14) | - | - | 0.15 | 0.71 (0.45–1.13) | - | - |
Tumour size (T1-T2 vs. T3-T4) | 0.0001 | 1.75 (1.33–2.31) | 0.02 | 1.50 (1.07–2.11) | <0.0001 | 2.16 (1.62–2.88) | 0.01 | 1.56 (1.11–2.19) |
Lymph nodes involvement (N0 vs. N+) | 0.07 | 1.47 (1.11–1.93) | 0.16 | 1.28 (0.91–1.81) | <0.0001 | 2.25 (1.70–2.98) | 0.0001 | 2.04 (1.41–2.95) |
pM | 0.03 | 9.4405 (1.29–68,82) | 0.12 | 5.01 (0.67–3.68) | 0.88 | 1.09 (0.35–3.42) | - | - |
Characteristics | NSCLC (N = 700) | AC (N = 330) | SCC (N = 370) | ||||||
---|---|---|---|---|---|---|---|---|---|
POSTN Expression by CAFs | POSTN Expression by CAFs | POSTN Expression by CAFs | |||||||
Low | High | Chi2 Test p-Value | Low | High | p-Value | Low | High | Chi2 Test p-Value | |
n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | ||||
Age | |||||||||
≤63 | 182 (26%) | 194 (27.7%) | 0.76 | 101 (30.6%) | 89 (27%) | 0.33 | 81 (21.9%) | 105 (28.4%) | 0.99 |
>63 | 158 (22.6%) | 166 (23.7%) | 78 (23.6%) | 62 (18.8%) | 80 (21.6%) | 104 (28.1%) | |||
Tumour size | |||||||||
pT1 | 97 (13.9%) | 75 (10.7%) | 0.03 | 52 (15.8%) | 27 (8.2%) | 0.03 | 45 (12.2%) | 48 (13%) | 0.27 |
pT2–pT4 | 243 (34.7%) | 285 (40.7%) | 127 (38.5%) | 124 (37.6%) | 116 (31.4%) | 161 (43.6%) | |||
Grade | |||||||||
G1 | 37 (5.3%) | 5 (0.7%) | <0.0001 | 31 (9.4%) | 1 (0.3%) | <0.0001 | 6 (1.6%) | 6 (1.6%) | 0.15 |
G2 | 247 (35.3%) | 271 (38.7%) | 111 (33.6%) | 106 (32.1%) | 136 (36.8%) | 165 (44.6%) | |||
G3 | 53 (7.6%) | 87 (12.4%) | 35 (10.6%) | 46 (13.9%) | 18 (4.9%) | 39 (10.5%) | |||
Lymph node involvement | |||||||||
pN0 | 238 (34%) | 211 (30.1%) | 0.005 | 126 (38.2%) | 83 (25.2%) | 0.02 | 112 (30.3%) | 128 (34.6%) | 0.1 |
pN1, N2 | 102 (14.6%) | 149 (21.3%) | 53 (16.1%) | 68 (20.6%) | 49 (13.2%) | 81 (21.9%) | |||
Stage | |||||||||
I | 149 (21.3%) | 105 (15%) | 0.0001 | 83 (25.2%) | 40 (12.1%) | 0.0006 | 65 (17.6%) | 66 (17.8%) | 0.1 |
II-IV | 191 (27.3%) | 255 (36.4%) | 96 (29.1%) | 111 (33.6%) | 95 (25.7%) | 144 (38.9%) |
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Ratajczak-Wielgomas, K.; Kmiecik, A.; Grzegrzołka, J.; Piotrowska, A.; Gomulkiewicz, A.; Partynska, A.; Pawelczyk, K.; Nowinska, K.; Podhorska-Okolow, M.; Dziegiel, P. Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer. Int. J. Mol. Sci. 2020, 21, 7025. https://doi.org/10.3390/ijms21197025
Ratajczak-Wielgomas K, Kmiecik A, Grzegrzołka J, Piotrowska A, Gomulkiewicz A, Partynska A, Pawelczyk K, Nowinska K, Podhorska-Okolow M, Dziegiel P. Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer. International Journal of Molecular Sciences. 2020; 21(19):7025. https://doi.org/10.3390/ijms21197025
Chicago/Turabian StyleRatajczak-Wielgomas, Katarzyna, Alicja Kmiecik, Jedrzej Grzegrzołka, Aleksandra Piotrowska, Agnieszka Gomulkiewicz, Aleksandra Partynska, Konrad Pawelczyk, Katarzyna Nowinska, Marzenna Podhorska-Okolow, and Piotr Dziegiel. 2020. "Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer" International Journal of Molecular Sciences 21, no. 19: 7025. https://doi.org/10.3390/ijms21197025