CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Immunostaining
2.3. Measurement of CSF1R Expression in TAMs
2.4. Detection of EGFR and KRAS Mutations and ALK Fusions
2.5. Statistical Analysis
3. Results
3.1. CSF1R Expression in TAMs
3.2. Association of CSF1R Expression in TAMs with Survival in Patients with Lung Adenocarcinoma
3.3. Association of CSF1R Expression in TAMs with Survival, Stratified by Smoking Status
3.4. Association of CSF1R Expression in TAMs with Survival in Female Patients, Stratified by Smoking Status
4. Discussion
5. Conclusion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
BSA | bovine serum albumin |
CI | confidence interval |
DAB | diaminobenzidine |
HR | hazard ratio |
JFCR | Japanese Foundation for Cancer Research |
PBS | phosphate-buffered saline |
PID | phosphor-integrated dot |
SNP | single nucleotide polymorphism |
TAM | tumor-associated macrophage |
References
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Variables | N of Samples (%) | CSF1R Expression | ||
---|---|---|---|---|
Low–Moderate 130 (67%) | High 65 (33%) | p Values | ||
Age (years) | 0.40 | |||
<60 | 73 (37%) | 46 (35%) | 27 (42%) | |
≥60 | 122 (63%) | 84 (65%) | 38 (58%) | |
Gender | 0.92 | |||
Male | 106 (54%) | 71 (55%) | 35 (54%) | |
Female | 89 (47%) | 59 (45%) | 30 (46%) | |
Smoking status | 0.54 | |||
Never smoker | 84 (43%) | 54 (42%) | 30 (46%) | |
Ever smoker | 111 (57%) | 76 (58%) | 35 (54%) | |
Pathological stage | 0.68 | |||
I | 112 (57%) | 76 (58%) | 36 (55%) | |
II–IV | 83 (43%) | 54 (42%) | 29 (45%) | |
Tumor differentiation | 0.012 | |||
Well | 84 (43%) | 64 (50%) | 20 (31%) | |
Moderate–poor | 110 (57%) | 65 (50%) | 45 (69%) | |
EGFR status | 0.11 | |||
Wild-type | 71 (54%) | 54 (59%) | 17 (44%) | |
Mutant | 60 (46%) | 38 (41%) | 22 (56%) | |
KRAS status | 0.22 | |||
Wild-type | 114 (87%) | 78 (85%) | 36 (92%) | |
Mutant | 17 (13%) | 14 (15%) | 3 (7.7%) | |
ALK rearrangement | 0.43 | |||
Negative | 187 (96%) | 124 (95%) | 64 (98%) | |
Positive | 7 (3.6%) | 6 (4.6%) | 1 (1.5%) | |
Number of TAMs | 0.83 | |||
Low–moderate | 131 (67%) | 88 (68%) | 43 (66%) | |
High | 64 (33%) | 42 (32%) | 22 (34%) |
Patients and CSF1R Expression Status | Lung Cancer-Specific Mortality | Overall Mortality | ||||||
---|---|---|---|---|---|---|---|---|
Univariable Analysis | Multivariable Analysis ** | Univariable Analysis | Multivariable Analysis ** | |||||
HR (95% CI) | p Values | HR (95% CI) | p Values | HR (95% CI) | p Values | HR (95% CI) | p Values | |
All patients | ||||||||
CSF1R: low–moderate expression (N = 130) | 1 (referent) | 1 (referent) | 1 (referent) | 1 (referent) | ||||
CSF1R: high expression (N = 65) | 1.61 (1.02–2.52) | 0.043 | 1.32 (1.00–2.49) | 0.048 | 1.31 (0.87–1.95) | 0.19 | 1.09 (0.72–1.65) | 0.68 |
Never-smoking patients | ||||||||
CSF1R: low–moderate expression (N = 54) | 1 (referent) | 1 (referent) | 1 (referent) | 1 (referent) | ||||
CSF1R: high expression (N = 30) | 2.90 (1.41–6.11) | 0.0041 | 2.66 (1.28–5.66) | 0.0088 | 2.63 (1.37–5.09) | 0.0038 | 2.21 (1.05–4.77) | 0.037 |
Ever-smoking patients | ||||||||
CSF1R: low–moderate expression (N = 76) | 1 (referent) | 1 (referent) | 1 (referent) | 1 (referent) | ||||
CSF1R: high expression (N = 35) | 1.11 (0.59–2.00) | 0.73 | 1.21 (0.65–2.19) | 0.54 | 0.84 (0.48–1.43) | 0.53 | 0.84 (0.47–1.43) | 0.52 |
p values for interaction *** | 0.049 | 0.12 | 0.0078 | 0.062 |
Patients and CSF1R Expression Status | Lung Cancer-Specific Mortality | Overall Mortality | ||||||
---|---|---|---|---|---|---|---|---|
Univariable Analysis | Multivariable Analysis ** | Univariable Analysis | Multivariable Analysis ** | |||||
HR (95% CI) | p Values | HR (95% CI) | p Values | HR (95% CI) | p Values | HR (95% CI) | p Values | |
Female patients | ||||||||
CSF1R: low–moderate expression (N = 59) | 1 (referent) | 1 (referent) | 1 (referent) | 1 (referent) | ||||
CSF1R: high expression (N = 30) | 2.28 (1.07–4.88) | 0.033 | 4.16 (1.62–11.0) | 0.0034 | 2.23 (1.13–4.39) | 0.021 | 2.37 (1.19–4.73) | 0.015 |
Never-smoking female patients | ||||||||
CSF1R: low–moderate expression (N = 48) | 1 (referent) | 1 (referent) | 1 (referent) | 1 (referent) | ||||
CSF1R: high expression (N = 22) | 2.78 (1.22–6.32) | 0.015 | 3.31 (1.42–7.80) | 0.0060 | 2.69 (1.30–5.53) | 0.0081 | 3.18 (1.50–6.76) | 0.0028 |
Ever-smoking female patients | ||||||||
CSF1R: low–moderate expression (N = 11) | 1 (referent) | 1 (referent) | 1 (referent) | 1 (referent) | ||||
CSF1R: high expression (N = 8) | 1.33 (0.16–11.1) | 0.77 | 0.92 (0.11–7.86) | 0.93 | 1.33 (0.16–11.1) | 0.77 | 0.92 (0.11–7.86) | 0.93 |
p values for interaction *** | 0.49 | 0.29 | 0.51 | 0.31 |
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Share and Cite
Inamura, K.; Shigematsu, Y.; Ninomiya, H.; Nakashima, Y.; Kobayashi, M.; Saito, H.; Takahashi, K.; Futaya, E.; Okumura, S.; Ishikawa, Y.; et al. CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining. Cancers 2018, 10, 252. https://doi.org/10.3390/cancers10080252
Inamura K, Shigematsu Y, Ninomiya H, Nakashima Y, Kobayashi M, Saito H, Takahashi K, Futaya E, Okumura S, Ishikawa Y, et al. CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining. Cancers. 2018; 10(8):252. https://doi.org/10.3390/cancers10080252
Chicago/Turabian StyleInamura, Kentaro, Yasuyuki Shigematsu, Hironori Ninomiya, Yasuhiro Nakashima, Maki Kobayashi, Haruyuki Saito, Katsuhiro Takahashi, Etsuko Futaya, Sakae Okumura, Yuichi Ishikawa, and et al. 2018. "CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining" Cancers 10, no. 8: 252. https://doi.org/10.3390/cancers10080252