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The expression and clinical significance of CLIC1 and HSP27 in lung adenocarcinoma

  • Research Article
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Tumor Biology

Abstract

The purpose of this research was to study the roles of chloride intracellular channel protein 1 (CLIC1) and heat shock protein 27 (HSP27) in the clinical pathology of lung adenocarcinoma and to explore whether the expression of CLIC1 and HSP27 can be used as independent factors for the prediction of recurrence and prognosis after radical resection of lung adenocarcinoma. One hundred and three paraffin sections of lung adenocarcinoma tissues were collected, and the expression of CLIC1 and HSP27 was detected in these tumors using immunohistochemistry. The correlation of the expression of these two proteins with clinicopathological parameters and prognosis was statistically analyzed. In the 103 samples, the expression of HSP27 and CLIC1 was strongly positive in 61 (59.2%) and 49 cases (47.6%), respectively. Statistical analysis showed that the expression level of HSP27 did not significantly correlate with the patient’s age, sex, degree of tumor differentiation, T staging of tumors, and TNM staging of tumors (p > 0.05), whereas the expression of CLIC1 did significantly correlate with T staging of tumors (p = 0.029). Univariate analysis indicated that the patient’s ECOG score, T staging, N staging, TNM staging, and CLIC1 expression correlated with prognosis (p = 0.031, 0.001, 0.011, 0.013, and <0.001, respectively). Multivariate statistical analysis showed that age, T staging, and CLIC1 expression were independent associated factors for predicting the 5-year survival rate of patients (p = 0.026, 0.004, and <0.001, respectively). Age, T staging, and CLIC1 expression significantly correlated with the overall survival of post-operative lung adenocarcinoma patients. CLIC1 may be closely associated with the occurrence and development of lung adenocarcinoma and may be used as an effective marker for predicting the prognosis of this disease.

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References

  1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Li HL, Qiu Y, Zhang X, et al. Establishment of a lung cancer biobank of a southern Chinese population. J Thorac Dis. 2009;1:17–22.

    Google Scholar 

  3. Bethune G, Bethune D, Ridgway N, et al. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2010;2:48–51.

    CAS  Google Scholar 

  4. Rena O, Carsana L, Cristina S, et al. Lymph node isolated tumor cells and micrometastases in pathological stage I non-small cell lung cancer: prognostic significance. Eur J Cardiothorac Surg. 2007;32:863–7.

    Article  PubMed  Google Scholar 

  5. Ruffato A, Mattioli S, Pileri S, et al. Do bone marrow isolated tumor cells influence long-term survival of non-small cell lung cancer? Eur J Cardiothorac Surg. 2009;35:463–8.

    Article  PubMed  Google Scholar 

  6. Shao WL, Wang DY, He JX. The role of gene expression profiling in early-stage non-small cell lung cancer. J Thorac Dis. 2010;2:89–99.

    CAS  Google Scholar 

  7. Nakamura N, Kobayashi K, Nakamoto M, et al. Identification of tumor markers and differentiation markers for molecular diagnosis of lung adenocarcinoma. Oncogene. 2006;25:4245–55.

    Article  PubMed  CAS  Google Scholar 

  8. Méndez M, Custodio A, Provencio M. New molecular targeted therapies for advanced non-small-cell lung cancer. J Thorac Dis. 2011;3:30–56.

    Google Scholar 

  9. Liu YF, Xiao ZQ, Li MX, et al. Quantitative proteome analysis reveals annexin A3 as a novel biomarker in lung adenocarcinoma. J Pathol. 2009;217:54–64.

    Article  PubMed  CAS  Google Scholar 

  10. Hollander JM, Martin JL, Belke DD. Overexpression of wild- type heat shock protein 27 and a nonphosphorylatable heat shock protein 27 mutant protects against ischemia/reperfusion injury in a transgenic mouse model. Circulation. 2004;110:3544–52.

    Article  PubMed  CAS  Google Scholar 

  11. Fincham VJ, James M, Frame MC, et al. Active ERK/MAPkinase15 targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src. EMBOJ. 2000;19:2911–23.

    Article  CAS  Google Scholar 

  12. Lomnytska MI, Becker S, Bodin I, et al. Differential expression of ANXA6, HSP27, PRDX2, NCF2, and TPM4 during uterine cervix carcinogenesis: diagnostic and prognostic value. Br J Canc. 2011;104:110–9.

    Article  CAS  Google Scholar 

  13. Lo Muzio L, Leonardi R, Mariggio MA, et al. HSP 27 as possible prognostic factor in patients with oral squamous cell carcinoma. Histol Histopathol. 2004;9:119–28.

    Google Scholar 

  14. King KL, Li AF, Chau GY, et al. Prognostic significance of heat shock protein-27 expression in hepatocellular carcinoma and its relation to histologic grading and survival. Cancer. 2000;88:2464–70.

    Article  PubMed  CAS  Google Scholar 

  15. Glaessgen A, Jonmarker S, Lindberg A, et al. Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer. APMIS. 2008;116:888–95.

    Article  PubMed  Google Scholar 

  16. Tweedle EM, Khattak I, Ang CW, et al. Low molecular weight heat shock protein HSP27 is a prognostic indicator in rectal cancer but not colon cancer. Gut. 2010;59:1501–10.

    Article  PubMed  CAS  Google Scholar 

  17. Romani AA, Crafa P, Desenzani S, et al. The expression of HSP27 is associated with poor clinical outcome in intrahepatic cholangiocarcinoma. BMC Cancer. 2007;7:232.

    Article  PubMed  Google Scholar 

  18. Malusecka E, Krzyzowska-Gruca S, Gawrychowski J, et al. Stress proteins HSP27 and HSP70i predict survival in non-small cell lung carcinoma. Anticancer Res. 2008;28:501–6.

    PubMed  Google Scholar 

  19. Tulk BM, Kapadia S, Edwards JC. CLIC1 inserts from the aqueous phase into phospholipid membranes, where it functions as an anion channel. Am J Physiol Cell Physiol. 2002;282:1103–12.

    Google Scholar 

  20. Chang YH, Wu CC, Chang KP, et al. Cell secretome analysis using hollow fiber culture system leads to the discovery of CLIC1 protein as a novel plasma marker for nasopharyngeal carcinoma. J Proteome Res. 2009;8:5465–74.

    Article  PubMed  CAS  Google Scholar 

  21. Shi ZH, Zhao C, Wu H, et al. CLIC1 protein: a candidate prognostic biomarker for malignant-transformed hydatidiform moles. Int J Gynecol Cancer. 2011;21:153–60.

    Article  PubMed  Google Scholar 

  22. Liu XY, Wang YF, Zhu HR. Interaction of Sedlin with PAM14. J Cell Biochem. 2010;109:1129–33.

    PubMed  CAS  Google Scholar 

  23. Valenzuela SM, Mazzanti M, Tonini R, et al. The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle. J Physiol. 2000;529:541–52.

    Article  PubMed  CAS  Google Scholar 

  24. Sun HJ, Bahk YY, Choi YR, et al. A proteomic analysis during serial subculture and osteogenic differentiation of human mesenchymal stem cell. J Orthop Res. 2006;24:2059–71.

    Article  PubMed  CAS  Google Scholar 

  25. Rahman A, Kumar SG, Kim SW, et al. Proteomic analysis for inhibitory effect of chitosan oligosaccharides on 3T3-L1 adipocyte differentiation. Proteomics. 2008;8:569–81.

    Article  PubMed  CAS  Google Scholar 

  26. Chen CD, Wang CS, Huang YH, et al. Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance. Proteomics. 2007;7:155–67.

    Article  PubMed  CAS  Google Scholar 

  27. Petrova DT, Asif AR, Armstrong VW, et al. Expression of chloride intracellular channel protein 1 (CLIC1) and tumor protein D52 (TPD52) as potential biomarkers for colorectal cancer. Clin Biochem. 2008;41:1224–36.

    Article  PubMed  CAS  Google Scholar 

  28. Huang JS, Chao CC, Su TL, et al. Diverse cellular transformation capability of overexpressed genes in human hepatocellular carcinoma. Biochem Biophys Res Commun. 2004;315:4950–8.

    Article  Google Scholar 

  29. Kim W, Oe Lim S, Kim JS, et al. Comparison of proteome between hepatitis B virus- and hepatitis C virus-associated hepatocellular carcinoma. Clin Cancer Res. 2003;9:5493–500.

    PubMed  CAS  Google Scholar 

  30. Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007;2:706–14.

    Article  PubMed  Google Scholar 

  31. Travis WD. World Health Organization, International Agency for Research on Cancer, International Academy of Pathology and International Association for the Study of Lung Cancer. Pathology and genetics of tumours of the lung, pleura, thymus, and heart. Lyon: IARC Press;2004.

  32. Li Z, Zhao X, Bai S, et al. Proteomics identification of cyclophilin a as a potential prognostic factor and therapeutic target in endometrial carcinoma. Mol Cell Proteomics. 2008;7:1810–23.

    Article  PubMed  CAS  Google Scholar 

  33. Zhu CQ, Shih W, Ling CH, et al. Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol. 2006;59:790–800.

    Article  PubMed  CAS  Google Scholar 

  34. Kapranos N, Kominea A, Konstantinopoulos PA, et al. Expression of the 27-kDa heat shock protein (HSP27) in gastric carcinomas and adjacent normal, metaplastic, and dysplastic gastric mucosa, and its prognostic significance. J Cancer Res Clin Oncol. 2002;128:426–32.

    Article  PubMed  CAS  Google Scholar 

  35. Selicharová I, Smutná K, Sanda M, et al. 2-DE analysis of a new human cell line EM-G3 derived from breast cancer progenitor cells and comparison with normal mammary epithelial cells. Proteomics. 2007;7:1549–59.

    Article  PubMed  Google Scholar 

  36. Tomonaga T, Matsushita K, Yamaguchi S, et al. Identification of altered protein expression and post-translational modifications in primary colorectal cancer by using agarose two-dimensional gel electrophoresis. Clin Cancer Res. 2004;10:2007–14.

    Article  PubMed  CAS  Google Scholar 

  37. Yancik R. Cancer burden in the aged: an epidemiologic and demographic overview. Cancer. 1997;80:1273–83.

    Article  PubMed  CAS  Google Scholar 

  38. Janssen-Heijnen ML, Smulders S, Lemmens VE, et al. Effect of comorbidity on the treatment and p rognosis of elderly patientswith non-small cell lung cancer. Thorax. 2004;59:602–7.

    Article  PubMed  CAS  Google Scholar 

  39. Li Z, Yu Y, Lu J, et al. Analysis of the T descriptors and other prognosis factors in pathologic stage I non-small cell lung cancer in China. J Thorac Oncol. 2009;4:702–9.

    Article  PubMed  Google Scholar 

  40. Chabowski M, Orłowski TM, Rabczenko D. Analysis of prognostic factors and efficacy of surgical treatment for non-small cell lung cancer: department of surgery NTLDRI (1998–1999). Pneumonol Alergol Pol. 2008;76:1–10.

    PubMed  Google Scholar 

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Conflicts of interest

None.

Funding

This study was supported by Science and Technology Planning Project of Guangdong Province, China (Nos: 2007B031515017 and 2008A030201024). This work was also supported by Science and Technology Planning Project of Guangzhou, China (Nos: 2007Z1-E0111 and 2007Z3-E0261).

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, People’s Republic of China

    Wei Wang, Xin Xu, Wujun Wang, Wenlong Shao, Weiqiang Yin & Jianxing He

  2. Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease, Guangzhou, People’s Republic of China

    Wei Wang, Xin Xu, Wenlong Shao, Weiqiang Yin, Jin Zhao & Jianxing He

  3. Department of Thoracic and Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China

    Wei Wang

  4. Guangdong Cardiovascular Institute, Southern Medical University, Guangzhou, People’s Republic of China

    Xin Xu, Wenlong Shao & Jianxing He

  5. Institute of Life and Health Engineering/National Engineering and Research Center for Genetic Medicine, Jinan University, Guangzhou, People’s Republic of China

    Liping Li & Qingyu He

  6. School of Public Health, Guangdong Medical College, Dongguan, People’s Republic of China

    Liangchang Xiu

  7. Department of Pathology, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, People’s Republic of China

    Mingcong Mo

  8. Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiang Rd, Guangzhou, 510120, Guangdong Province, People’s Republic of China

    Jianxing He

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  1. Wei Wang
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  2. Xin Xu
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  3. Wujun Wang
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  4. Wenlong Shao
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  8. Mingcong Mo
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  9. Jin Zhao
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  10. Qingyu He
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  11. Jianxing He
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Corresponding authors

Correspondence to Qingyu He or Jianxing He.

Additional information

Wei Wang and Xin Xu have contributed equally to this work.

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Wang, W., Xu, X., Wang, W. et al. The expression and clinical significance of CLIC1 and HSP27 in lung adenocarcinoma. Tumor Biol. 32, 1199–1208 (2011). https://doi.org/10.1007/s13277-011-0223-0

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  • DOI: https://doi.org/10.1007/s13277-011-0223-0

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