Skip to main content
SpringerLink
Log in

Thrombocytosis and immunohistochemical expression of connexin 43 at diagnosis predict survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

An Erratum to this article was published on 17 May 2013

Abstract

Purpose

Patients with advanced non-small-cell lung cancer (NSCLC) have poor survival, and platinum-based chemotherapy agents are the standard first-line chemotherapy agents for advanced NSCLC. This study aimed to identify predictive factors associated with the response to chemotherapy and survival in 258 patients with advanced NSCLC treated with platinum-based chemotherapy.

Methods

Stage IIIA–IV NSCLC patients diagnosed in Kaifeng second people’s hospital (Henan, China) between March 2002 and September 2011 were retrospectively reviewed. All of the patients had received platinum-based chemotherapy, and patients were followed up to date of death or last follow-up to obtain data of response to chemotherapy and survival. Potential prognostic factors such as gender, age, tumor size, tumor type, histologic stage, anemia, calcium levels, ECOG performance status (PS), thrombocytosis, TTF-1, p63, and connexin 43 were analyzed. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan–Meier method and Cox regression model.

Results

A univariate analysis indicated that thrombocytosis and connexin 43 were found to be significant prognostic factors (p < 0.001) and ECOG PS, Hb levels, and p63 presented a tendency toward association with survival. Kaplan–Meier survival showed that the mean OS and PFS in chemotherapy responders with connexin 43 ≥+2 were significantly longer than in chemotherapy responders with connexin 43 ≤1+. In contrast, thrombocytosis was associated with increased mortality and resistance to chemotherapy in chemotherapy responders. In addition, all 21 patients of the 5-year OS were from chemotherapy responders with connexin 43 ≥+2 or non-thrombocytosis.

Conclusions

Thrombocytosis and connexin 43 absence may be reliable surrogate markers for the prediction of chemotherapy response and prognosis for patients with advanced NSCLC, and assessment of these factors may identify a population of patients with advanced NSCLC that is likely to have a prolonged life expectancy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Siegel R, Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29

    Article  PubMed  Google Scholar 

  2. Kim DN, Nam TK, Choe KS, Choy H (2012) Personalized combined modality therapy for locally advanced non-small cell lung cancer. Cancer Res Treat 44:74–84

    Article  PubMed  Google Scholar 

  3. Lee DS, Kim YS, Kang JH, Lee SN, Kim YK, Ahn MI, Han DH, Yoo IR, Wang YP, Park JG, Yoon SC, Jang HS, Choi BO (2011) Clinical responses and prognostic indicators of concurrent chemoradiation for non-small cell lung cancer. Cancer Res Treat 43:32–41

    Article  PubMed  Google Scholar 

  4. Mandrekar SJ, Schild SE, Hillman SL, Allen KL, Marks RS, Mailliard JA, Krook JE, Maksymiuk AW, Chansky K, Kelly K, Adjei AA, Jett JR (2006) A prognostic model for advanced stage nonsmall cell lung cancer. Pooled analysis of North Central Cancer Treatment Group trials. Cancer 107:781–792

    Article  PubMed  Google Scholar 

  5. Belbaraka R, Trédan O, Ray-Coquard I, Chvetzoff G, Bajard A, Pérol D, Ismaili N, Ismaili M, Errihani H, Bachelot T, Rebattu P (2010) Factors of interrupting chemotherapy in patients with advanced non-small-cell lung cancer. BMC Res Notes 3:164

    Article  PubMed  Google Scholar 

  6. Berghmans T, Paesmans M, Sculier JP (2011) Prognostic factors in stage III non-small cell lung cancer: a review of conventional, metabolic and new biological variables. Ther Adv Med Oncol 3:127–138

    Article  PubMed  Google Scholar 

  7. Ota S, Ishii G, Goto K, Kubota K, Kim YH, Kojika M, Murata Y, Yamazaki M, Nishiwaki Y, Eguchi K, Ochiai A (2009) Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy. Lung Cancer 64:98–104

    Article  PubMed  Google Scholar 

  8. Krawczyk P, Wojas-Krawczyk K, Mlak R, Kucharczyk T, Biernacka B, Milanowski J (2012) Predictive value of ERCC1 single-nucleotide polymorphism in patients receiving platinum-based chemotherapy for locally-advanced and advanced non-small cell lung cancer—a pilot study. Folia Histochem Cytobiol 50:80–86

    Article  PubMed  CAS  Google Scholar 

  9. Yin JY, Huang Q, Zhao YC, Zhou HH, Liu ZQ (2012) Meta-analysis on pharmacogenetics of platinum-based chemotherapy in non small cell lung cancer (NSCLC) patients. PLoS ONE 7:e38150

    Article  PubMed  CAS  Google Scholar 

  10. Gibbs AR, Thunnissen FB (2001) Histological typing of lung and pleural tumours: third edition. J Clin Pathol 54:498–499

    Article  PubMed  CAS  Google Scholar 

  11. Laird DW (2006) Life cycle of connexins in health and disease. Biochem J 394:527–543

    Article  PubMed  CAS  Google Scholar 

  12. Darr EA, Patel AD, Yu G, Komorowski Z, McCormick S, Tiwari R, Schantz SP, Geliebter J (2011) Reduced Cx43 gap junction plaque expression differentiates thyroid carcinomas from benign disease. Arch Otolaryngol Head Neck Surg 137:1161–1165

    Article  PubMed  Google Scholar 

  13. Sirnes S, Bruun J, Kolberg M, Kjenseth A, Lind GE, Svindland A, Brech A, Nesbakken A, Lothe RA, Leithe E, Rivedal E (2012) Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease outcome. Int J Cancer 131:570–581

    Article  PubMed  CAS  Google Scholar 

  14. Zhao W, Han HB, Zhang ZQ (2011) Suppression of lung cancer cell invasion and metastasis by connexin 43 involves the secretion of follistatin-like 1 mediated via histone acetylation. Int J Biochem Cell Biol 43:1459–1468

    Article  PubMed  CAS  Google Scholar 

  15. Plante I, Stewart MK, Barr K, Allan AL, Laird DW (2011) Cx43 suppresses mammary tumor metastasis to the lung in a Cx43 mutant mouse model of human disease. Oncogene 30:1681–1692

    Article  PubMed  CAS  Google Scholar 

  16. Yu SC, Xiao HL, Jiang XF, Wang QL, Li Y, Yang XJ, Ping YF, Duan JJ, Jiang JY, Ye XZ, Xu SL, Xin YH, Yao XH, Chen JH, Chu WH, Sun W, Wang B, Wang JM, Zhang X, Bian XW (2012) Connexin 43 reverses malignant phenotypes of glioma stem cells by modulating E-cadherin. Stem Cells 30:108–120

    Article  PubMed  CAS  Google Scholar 

  17. Xu HT, Li QC, Zhang YX, Zhao Y, Liu Y, Yang ZQ, Wang EH (2008) Connexin 43 recruits E-cadherin expression and inhibits the malignant behaviour of lung cancer cells. Folia Histochem Cytobiol 46:315–321

    Article  PubMed  CAS  Google Scholar 

  18. Bui MM, Han G, Acs G, Reed D, Gonzalez RJ, Pasha TL, Zhang PJ (2011) Connexin 43 is a potential prognostic biomarker for ewing sarcoma/primitive neuroectodermal tumor. Sarcoma 2011:971050

    Article  PubMed  Google Scholar 

  19. Jinn Y, Inase N (2010) Connexin 43, E-cadherin, beta-catenin and ZO-1 expression, and aberrant methylation of the connexin 43 gene in NSCLC. Anticancer Res 30:2271–2278

    PubMed  CAS  Google Scholar 

  20. Cakar B, Karaoglanoglu M, Sayici Y, Gonullu Demirag G, Yucel I (2011) The prognostic value of thrombocytosis in newly diagnosed lung cancer patients: a retrospective analysis. J BUON 16:677–681

    PubMed  CAS  Google Scholar 

  21. Stone RL, Nick AM, McNeish IA, Balkwill F, Han HD, Bottsford-Miller J, Rupaimoole R, Armaiz-Pena GN, Pecot CV, Coward J, Deavers MT, Vasquez HG, Urbauer D, Landen CN, Hu W, Gershenson H, Matsuo K, Shahzad MM, King ER, Tekedereli I, Ozpolat B, Ahn EH, Bond VK, Wang R, Drew AF, Gushiken F, Collins K, DeGeest K, Lutgendorf SK, Chiu W, Lopez-Berestein G, Afshar-Kharghan V, Sood AK (2012) Paraneoplastic thrombocytosis in ovarian cancer. N Engl J Med 366:610–618

    Article  PubMed  CAS  Google Scholar 

  22. Hwang SG, Kim KM, Cheong JH, Kim HI, An JY, Hyung WJ, Noh SH (2012) Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of gastric cancer. Eur J Surg Oncol 38:562–567

    Article  PubMed  CAS  Google Scholar 

  23. Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T (2009) Preoperative leukocytosis, anemia and thrombocytosis are associated with poor survival in non-small cell lung cancer. Anticancer Res 29:2687–2690

    PubMed  Google Scholar 

  24. Lin MS, Huang JX, Zhu J, Shen HZ (2012) Elevation of platelet count in patients with colorectal cancer predicts tendency to metastases and poor prognosis. Hepatogastroenterology 59:1687–1690

    PubMed  Google Scholar 

  25. Cravioto-Villanueva A, Luna-Perez P, Gutierrez-de la Barrera M, Martinez-Gómez H, Maffuz A, Rojas-Garcia P, Perez-Alvarez C, Rodriguez-Ramirez S, Rodriguez-Antezana E, Ramirez–Ramirez L (2012) Thrombocytosis as a predictor of distant recurrence in patients with rectal cancer. Arch Med Res 43:305–311

    Article  PubMed  Google Scholar 

  26. Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T (2008) Prognostic impact of thrombocytosis in resectable non-small cell lung cancer. Interact Cardiovasc Thorac Surg 7:613–615

    Article  PubMed  Google Scholar 

  27. Buergy D, Wenz F, Groden C, Brockmann MA (2012) Tumor-platelet interaction in solid tumors. Int J Cancer 130:2747–2760

    Article  PubMed  CAS  Google Scholar 

  28. Lamiche C, Clarhaut J, Strale PO, Crespin S, Pedretti N, Bernard FX, Naus CC, Chen VC, Foster LJ, Defamie N, Mesnil M, Debiais F, Cronier L (2012) The gap junction protein Cx43 is involved in the bone-targeted metastatic behaviour of human prostate cancer cells. Clin Exp Metastasis 29:111–122

    Article  PubMed  CAS  Google Scholar 

  29. Kargus S, Weber FE, Luebbers HT, Zemann W, Graetz KW, Kruse AL (2012) Pretreatment thrombocytosis: a prognostic marker for oral squamous cell carcinoma? Oral Maxillofac Surg 16:197–200

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81173094), the joint construction fund for Henan University from Henan Province and the Ministry of Education of China (No. SBGJ090704), and the Young Core Instructor of Henan Province, China (No. 2010GGJS-025).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Institute of Pharmacy, Pharmacy College of Henan University, Jinming street, Kaifeng, 475004, Henan, China

    Gangjun Du, Yaping Zhang, Ting Sun, Weijie Liu, Yingying Wang & Jiahuan Li

  2. Department of Oncology, Kaifeng Second People’s Hospital, Bianjing street, Kaifeng, 475001, Henan, China

    Yingming Yang & Houyun Zhang

Authors
  1. Gangjun Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yingming Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yaping Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ting Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Weijie Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yingying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jiahuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Houyun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Gangjun Du or Yingming Yang.

Additional information

Gangjun Du and Yingming Yang have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Du, G., Yang, Y., Zhang, Y. et al. Thrombocytosis and immunohistochemical expression of connexin 43 at diagnosis predict survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy. Cancer Chemother Pharmacol 71, 893–904 (2013). https://doi.org/10.1007/s00280-013-2080-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-013-2080-6

Keywords

Search

Navigation