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. 2012 Aug 28;31(1):70.
doi: 10.1186/1756-9966-31-70.

Upregulation of Hsp90-beta and annexin A1 correlates with poor survival and lymphatic metastasis in lung cancer patients

Rong Biaoxue  1 , Jiang Xiling, Yang Shuanying, Zhang Wei, Cai Xiguang, Wang Jinsui, Zhang Min
Affiliations

Upregulation of Hsp90-beta and annexin A1 correlates with poor survival and lymphatic metastasis in lung cancer patients

Rong Biaoxue et al. J Exp Clin Cancer Res. .

Abstract

Background: Hsp90-beta and annexin A1 were investigated as prognostic factors because of their apparent association with tumorigenesis. However, the effect of Hsp90-beta and annexin A1 in lung cancer remains poorly understood. The expressions of Hsp90-beta and annexin A1 in lung cancer and normal lung specimens were examined, and the relationships with respect to the clinico-pathological features and patient survival in lung cancer were analyzed.

Methods: The expression levels of Hsp90-beta and annexin A1 were examined using immunohistochemistry, in-situ hybridization, and Western blot.

Results: Lung cancer tissues exhibited higher expression levels of Hsp90-beta and annexin A1 than the normal tissues (p < 0.05), and the expression levels of the markers were significantly associated with the pathological grade and lymphatic invasion of lung cancer (p < 0.05). Moreover, the upregulation of Hsp90-beta and annexin A1 correlated with decreased survival (p < 0.05).

Conclusion: The upregulation of Hsp90-beta and annexin A1 were associated with poor post-surgical survival time and lymphatic metastasis of lung cancer patients. Moreover, the high expression of the markers was an independent predictor of poor outcomes.

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Figures

Figure 1
Figure 1
IHC analysis of Hsp90-beta and annexin A1 in lung cancer and normal lung tissues (IHC × 400). (A) Low staining of Hsp90-beta in normal tissues; (B) moderate staining of Hsp90-beta in moderately differentiated LAC; (C) high staining of Hsp90-beta in poorly differentiated LAC; (D) moderate staining of Hsp90-beta in moderately differentiated LSCC; (E) high staining of Hsp90-beta in poorly differentiated LSCC; (F) high staining of annexin A1 in LCLC; (G) low staining of annexin A1 in well-differentiated LAC; (H) moderate staining of annexin A1 in moderately differentiated LAC; (I) high staining of annexin A1 in poorly differentiated LAC; (J) high staining of annexin A1 in SCLC; (K) moderate staining of annexin A1 in moderately differentiated LSCC; (L) high staining of annexin A1 in poorly differentiated LSCC; LAC, adenocarcinoma of the lung; LSCC, squamous cell carcinoma of the lung; SCLC, small cell lung cancer; LCLC, large cell lung cancer.
Figure 2
Figure 2
Correlation between clinico-pathological features and the expression of Hsp90-beta and annexin A1 in lung cancer. (A and B) Upregulation of Hsp90-beta and annexin A1 was observed in poorly differentiated lung cancer tissues compared with well-differentiated tissues (p < 0.0005); (C and D) Hsp90-beta and annexin A1 expressions in lung cancer cases without lymphnode metastasis was lower than that in lung cancer cases with lymph node metastasis (p < 0.0005); (E and F) Upregulated Hsp90-beta and annexin A1 was found in lung cancer tissues at stages III to IV compared with that at stages I to II (p = 0.002).
Figure 3
Figure 3
ISH analysis of Hsp90-beta and annexin A1 mRNA in lung cancer and normal lung tissues (ISH × 400). (A) Low staining of Hsp90-beta mRNA in well-differentiated LAC; (B) moderate staining of Hsp90-beta mRNA in moderately differentiated LAC; (C) high staining of Hsp90-beta mRNA in poorly differentiated LAC; (D) low staining of Hsp90-beta mRNA in well-differentiated LSCC; (E) moderate staining of Hsp90-beta mRNA in moderately differentiated LSCC; (F) high staining of Hsp90-beta mRNA in poorly differentiated LSCC; (G) low staining of annexin A1 mRNA in well-differentiated LAC; (H) moderate staining of annexin A1 mRNA in moderately differentiated LAC; (I) high staining of annexin A1 mRNA in poorly differentiated LAC; (J) low staining of annexin A1 mRNA in well-differentiated LSCC; (K) moderate staining of annexin A1 mRNA in moderately differentiated LSCC; (L) high staining of annexin A1 mRNA in poorly differentiated LSCC; LAC, lung adenocarcinoma; LSCC, lung squamous cell carcinoma; SCLC, small cell lung cancer; and LCLC, large cell lung cancer.
Figure 4
Figure 4
Representative results of the Western blot of the expressions of Hsp90-beta and annexin A1 expression in the matched cancer tissues and adjacent normal tissues. The Western blot results indicated high expression levels of Hsp90-beta and annexin A1 in the cancer tissues than the adjacent normal tissues (p < 0.05); N = normal tissues; T = tumor tissues.
Figure 5
Figure 5
Kaplan-Meier survival curves for positive and negative expressions of Hsp90-beta and annexin A in lung cancer. (A) Among all 65 lung cancer cases, a higher expression of annexin A1 was associated with a longer post-surgery survival time (p = 0.014). (B) A higher expression of Hsp90-beta is also related to a longer post-surgery survival time (p = 0.021).
Figure 6
Figure 6
Protein expression of Hsp90-beta and annexin A1 in cell lines using Western blot analysis. Varied expression levels of Hsp90-beta and annexin A1 in cell levels were noted, but was generally upregulated in most lung cancer cell lines (except the H520) compared with the 16 HBE cell lines.
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