Up-Regulation of S100A11 in Lung Adenocarcinoma - Its Potential Relationship with Cancer Progression - PubMed (original) (raw)
Up-Regulation of S100A11 in Lung Adenocarcinoma - Its Potential Relationship with Cancer Progression
Tetsukan Woo et al. PLoS One. 2015.
Abstract
We previously reported that patients with lung adenocarcinomas with KRAS gene mutations and strong proliferating activity had poorer outcomes, even in the early stage of the disease. The aim of the present study was to elucidate the potential molecular basis of these highly malignant lung tumors by focusing on S100 proteins (S100A2, S100A7, and S100A11), which are downstream targets of oncogenic KRAS and promoters of tumor progression. The immunohistochemical expression of S100 proteins was examined in 179 primary lung adenocarcinomas, and the potential relationships between their levels and clinicopathologic factors were analyzed. Among the three subtypes, S100A11 levels were significantly higher in adenocarcinomas with KRAS mutations and strong proliferating activity. They were also higher in adenocarcinomas with poorly differentiated tumors. Furthermore, higher levels of S100A11 were associated with shorter disease-free survival. These results suggest that the up-regulation of S100A11 plays a role in tumor progression, particularly in KRAS-mutated lung adenocarcinomas.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
Fig 1. Immunohistochemical examination of S100A11 and S100A2 protein expression levels in tumors and non-tumorous epithelia from lung adenocarcinoma (ADC) patients undergoing surgical resection.
Representative photographs from normal bronchioles (A, E) and tumors, in which the expression of S100A11 and S100A2 was negative (B, F), weak (C, G) and strong (D, H), are shown.
Fig 2. The S100A11 and S100A2 expression levels in all tumors.
Median expression scores were 1.30 in S100A11 (A) and 0.10 in S100A2 (B). S100A11 was not expressed in 8 cases (A), while S100A2 was not expressed in nearly half of the cases examined (83 cases) (B). ADC, Adenocarcinoma.
Fig 3. S100A11 expression levels in adenocarcinomas with KRAS mutations and proliferating activity.
The thickened lines indicate the median score of S100 A11 expression, which was 1.00 in KRAS Wild-type/Ki-67 Low cases (n = 94), 1.50 in KRAS Wild-type/Ki-67 High cases (n = 62), 1.20 in KRAS Mutated-type/Ki-67 Low cases (n = 11) and 1.80 in KRAS Mutated-type/Ki-67 High cases (n = 11). S100A11 expression levels were significantly higher in adenocarcinomas with KRAS mutations and strong proliferating activity (P = 0.038 in the Kruskal-Wallis test). Wt, Wild-type; Mt, Mutated-type.
Fig 4. Kaplan-Meier Disease-free survival curves by S100A11 expression levels for stage I lung adenocarcinomas.
Five-year disease-free survival rates were 76.3% in high-S100A11 expressers (n = 61) and 90.1% in low-S100A11 expressers (n = 118). The strong expression of S100A11 correlated with shorter disease-free survival in post-operative lung adenocarcinomas (p = 0.0182 in the Log-rank test).
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This work was funded by the Ministry of Education, Culture, Sports, and Science of Japan (Tokyo Japan), and Yokohama Medical Facility (Yokohama, Japan). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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