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. 2013;8(1):e54674.
doi: 10.1371/journal.pone.0054674. Epub 2013 Jan 31.

Prognostic significance of the combined score of endothelial expression of nucleolin and CD31 in surgically resected non-small cell lung cancer

Hongyun Zhao  1 , Yan Huang, Cong Xue, Yang Chen, Xue Hou, Ying Guo, Liping Zhao, Zhi huang Hu, Yujie Huang, Yongzhang Luo, Li Zhang
Affiliations

Prognostic significance of the combined score of endothelial expression of nucleolin and CD31 in surgically resected non-small cell lung cancer

Hongyun Zhao et al. PLoS One. 2013.

Abstract

Nucleolin is implicated to play a role in angiogenesis, a vital process in tumor growth and metastasis. However, the presence and clinical relevance of nucleolin in human non small cell lung cancer (NSCLC) remains largely unknown. In this study, we explored the expression and prognostic implication of nucleolin in surgically resected NSCLC patients. A cohort of 146 NSCLC patients who underwent surgical resection was selected for tissue microarray. In this tissue microarray, nucleolin expression was measured by immunofluorescence. Staining for CD31, a marker of endothelial cells, was performed to mark blood vessels. A Cox proportional hazards model was used to assess the prognostic significance of nucleolin. Nucleolin expression was observed in 34.2% of all patients, and 64.1% in high CD31 expression patients. The disease-free survival (DFS) was significantly shorter in patients with high nucleolin (CD31(hi)NCL(hi)) compared to patients with low tumor blood vessels (CD31(lo)NCL(lo)) (5 ys of DFS 24% vs 64%, p = 0.002). Such a difference was demonstrated in the following stratified analyses: stage I (p<0.001), squamous cell carcinoma and adenosquamous cell carcinoma (p = 0.028), small tumor (<5 cm, p = 0.008), and surgery alone (p = 0.015). Multivariate analysis further revealed that nucleolin expression independently predicted for worse survival (p = 0.003). This study demonstrates that nucleolin is associated with the clinical outcomes in postoperative NSCLC patients. Thus, the expression levels of nucleolin may provide a new prognostic marker to identify patients at higher risk for treatment failure, especially in some subgroups.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The NSCLC sections were divided into three groups based on the blood vessel density and nucleolin expression.
The tumor blood vessels and nucleolin were stained with anti-CD31 (green) and anti-nucleolin (red), respectively. Nuclei were stained with DAPI (blue). Representative images from the three groups were shown here. (A) CD31hiNCLhi, (B) CD31hiNCLlo, (C) CD31loNCLlo. Scale bar, 50 µm.
Figure 2
Figure 2. Kaplan-Meier plots of DFS according to the expression of CD31 and nucleolin in the entire cohort.
HH: CD31hiNCLhi, HL: CD31hiNCLlo, and LL: CD31loNCLlo.
Figure 3
Figure 3. Kaplan-Meier plots of DFS according to the expression of CD31 and nucleolin in the subgroups: (A) Squamous cell carcinoma (SCC) and adenosquamous cell carcinoma (ADSCC), (B) Tumor size <5 cm, (C) Stage I, and (D) Surgery alone.
HH: CD31hiNCLhi, HL: CD31hiNCLlo, and LL: CD31loNCLlo.
See this image and copyright information in PMC

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