PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer
Abstract
:1. Introduction
2. Results
2.1. PAK1 Expression in NSCLC Cells/Fresh-Frozen NSCLC Specimens Was Higher than That in BEAS-2B Cells/Adjacent Healthy Lung Tissue Specimens
2.2. Association of PAK1 Expression with Histological NSCLC Subtypes and Clinicopathological Characteristics of Patients
2.3. Clinical Characteristics of Patients with EGFR Mutations Based on PAK1 Expression
2.4. Effects of PAK1 Overexpression on Five-Year and Recurrence-Free Survival
2.5. Effects of PAK1 Expression on Five-Year Survival Based on Sex and Smoking Status
3. Discussion
4. Materials and Methods
4.1. NSCLC Tissue Specimens and TMA Construction
4.2. Antibodies and Compounds
4.3. Cells and Culture Conditions
4.4. Western Blotting
4.5. RT-PCR
4.6. Immunohistochemistry
4.7. Analysis of Datasets
4.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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PAK1 Negative (%) (N = 90) | PAK1 Positive (%) (N = 111) | p Value | EGFR Mutation Negative (%) (N = 154) | EGFR Mutation Positive (%) (N = 47) | p Value | |
---|---|---|---|---|---|---|
Age (median) | 65.6 ± 10.2 | 64.1 ± 10.8 | 0.305 | 66.1 ± 10.1 | 60.5 ± 11.0 | 0.001 |
Sex (male) | 58 (64.4) | 94 (84.7) | 0.001 | 130 (84.4) | 22 (46.8) | <0.001 |
Smoking (current + former) | 47 (52.2) | 84 (75.7) | 0.001 | 115 (74.7) | 16 (34.0) | <0.001 |
Histologic subtype (adenoca vs squamous) | 64 (71.1) vs. 26 (28.9) | 56 (50.5) vs. 55 (49.5) | 0.003 | 74 (48.1) vs. 80 (51.9) | 46 (97.9) vs. 1 (2.1) | <0.001 |
Pathologic TNM stage (I vs. II+III+IV) | 59 (65.6) vs. 31 (34.4) | 54 (48.6) vs. 57 (88) | 0.016 | 79 (51.3) vs. 75 (48.7) | 34 (72.3) vs. 13 (27.7) | 0.011 |
T classification | 0.051 | 0.003 | ||||
T1 | 50 (55.6) | 45 (40.5) | 64 (41.6) | 31 (66.0) | ||
T2 | 35 (38.9) | 49 (44.1) | 71 (46.1) | 13 (27.7) | ||
T3 | 5 (5.6) | 14 (12.6) | 18 (11.7) | 1 (2.1) | ||
T4 | 0 (0) | 3 (2.7) | 1 (0.6) | 2 (4.3) | ||
N classification | 0.488 | 0.170 | ||||
N0 | 64 (71.1) | 68 (61.3) | 95 (61.7) | 37 (78.7) | ||
N1 | 15 (16.7) | 23 (20.7) | 33 (21.4) | 5 (10.6) | ||
N2 | 10 (11.1) | 19 (17.1) | 24 (15.6) | 5 (10.6) | ||
N3 | 1 (1.1) | 1 (0.9) | 2 (1.3) | 0 (0) | ||
M classification (M0 vs. M1) | 87 (96.7) vs. 3 (3.3) | 100 (90.0) vs. 11 (9.1) | 0.100 | 144 (94.1) vs. 9 (5.9) | 43 (91.5) vs. 4 (8.5) | 0.523 |
5-year survival (month) | 43.8 ± 20.0 | 40.9 ± 21.7 | 0.319 | 39.3 ± 21.6 | 51.6 ± 15.2 | <0.001 |
Differentiation (well to moderate vs. poor) | 71 (78.9) vs. 19 (21.1) | 80 (72.1) vs. 31 (27.9) | 0.266 | 110 (71.4) vs. 44 (28.6) | 41 (87.2) vs. 6 (12.8) | 0.028 |
Lymphovascular invasion | 67 (74.4) | 79 (71.2) | 0.605 | 47 (30.5) | 8 (17.0) | 0.069 |
PAK1 Negative (%) (N = 24) | PAK1 Positive (%) (N = 23) | p Value | |
---|---|---|---|
Age (median) | 58.4 ± 12.1 | 62.8 ± 9.3 | 0.172 |
Sex (male) | 15 (62.5) | 7 (30.4) | 0.028 |
Smoking (current + former) | 11 (45.8) | 5 (21.7) | 0.081 |
Histologic subtype (adenoca vs. squamous) | 23 (95.8) | 23 (100) | 0.322 |
T classification | 0.378 | ||
T1 | 15 (62.5) | 16 (69.6) | |
T2 | 6 (25.0) | 7 (30.4) | |
T3 | 1 (4.2) | 0 (0) | |
T4 | 2 (8.3) | 0 (0) | |
N classification | 0.816 | ||
N0 | 18 (75.0) | 19 (82.6) | |
N1 | 3 (12.5) | 2 (8.7) | |
N2 | 3 (12.5) | 2 (8.7) | |
N3 | 0 (0) | 0 (0) | |
M classification | 0.780 | ||
(M0 vs. M1) | 21 (87.5) vs. 3 (12.5) | 22 (95.7) vs. 1 (4.3) | |
Differentiation | 0.232 | ||
Well to moderate | 21 (37.5) | 20 (65.2) | |
Poor | 3 (12.5) | 3 (12.5) | |
Lymphovascular invasion | 4 (16.7) | 4 (17.4) | 0.947 |
5-year mortality rate | 15 (62.5) | 21 (91.3) | 0.020 |
Variables | 5-Year Survival | |||
---|---|---|---|---|
No. of Patients | Odd Ratio | 95% Confidential Interval | p Value | |
Sex (male) | 152/201 | 0.328 | 0.167 ± 0.643 | 0.001 |
Smoking (current + former) | 131/201 | 2.846 | 1.563 ± 5.180 | 0.001 |
Histologic subtype (adenoca) | 119/201 | 2.506 | 1.392 ± 4.514 | 0.002 |
Pathologic TNM stage (I vs. II + III + IV) | 113/201 | 2.009 | 1.133 ± 3.561 | 0.017 |
T classification (T1 vs. T2 + T3 + T4) | 94/201 | 1.753 | 0.999 ± 3.074 | 0.050 |
M classification (M0 vs. M1) | 187/201 | 3.190 | 0.862 ± 11.805 | 0.082 |
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Chung, J.H.; Kim, T.; Kang, Y.J.; Yoon, S.H.; Kim, Y.S.; Lee, S.K.; Son, J.H.; Son, B.; Kim, D.H. PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer. Molecules 2020, 25, 5588. https://doi.org/10.3390/molecules25235588
Chung JH, Kim T, Kang YJ, Yoon SH, Kim YS, Lee SK, Son JH, Son B, Kim DH. PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer. Molecules. 2020; 25(23):5588. https://doi.org/10.3390/molecules25235588
Chicago/Turabian StyleChung, Jae Heun, Taehwa Kim, Yong Jung Kang, Seong Hoon Yoon, Yun Seong Kim, Sung Kwang Lee, Joo Hyung Son, Bongsoo Son, and Do Hyung Kim. 2020. "PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer" Molecules 25, no. 23: 5588. https://doi.org/10.3390/molecules25235588