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Prognostic value of differential CCND1 expression in patients with resected gastric adenocarcinoma

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Abstract

Cyclin D1 (CCND1) plays essential roles in cancer progression. In this study, CCND1 expression patterns in 211 cases of resected gastric adenocarcinoma (RGA) tissue were determined by immunohistochemistry, and the association between CCND1 expression levels and RGA prognosis was analyzed. RGA tissues displayed differential CCND1 expression (high expression, 52.1 %; n = 110, and low expression, 47.9 %; n = 101). CCND1 expression levels were related with median overall survival time (MST). MST in patients with high CCND1 expression was 43 months, whereas with low CCND1 expression it was 62 months (P = 0.013). When data were stratified by postoperative treatments and CCND1 expression levels, the MST for patients treated with fluoropyrimidine plus platinum (n = 140) was significantly longer than for those treated with fluoropyrimidine only (n = 71) in both high and low CCND1 expression groups (65.0 vs. 29.0 months, P = 0.041; and 74.5 vs. 33.0 months, P = 0.003, respectively). Cox multivariate analyses further confirmed that high CCND1 expression was related with poor prognosis in both treatment groups [hazard ratio (HR) 1.91, 95 % confidence interval (CI) 1.12–3.23; P = 0.017, and HR 2.14, 95 % CI 1.08–4.25; P = 0.029] and that fluoropyrimidine plus platinum was more effective than fluoropyrimidine only in high CCND1 (HR 0.47, 95 % CI 0.28–0.78; P = 0.004) and low CCND1 (HR 0.44; 95 % CI 0.23–0.82; P = 0.01) expression patients. Therefore, CCND1 may be used as a prognostic biomarker for patients with RGA.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ. MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.

    Article  CAS  PubMed  Google Scholar 

  3. Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzén F, Noh SH. CLASSIC trial investigators. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379:315–21.

    Article  CAS  PubMed  Google Scholar 

  4. Andrews J, Yeh P, Pao W, Horn L. Molecular predictors of response to chemotherapy in non-small cell lung cancer. Cancer J. 2011;17:104–13.

    Article  CAS  PubMed  Google Scholar 

  5. Choi YJ, Anders L. Signaling through cyclin D-dependent kinases. Oncogene. 2014;33(15):1890–903.

    Article  CAS  PubMed  Google Scholar 

  6. Calipel A, Mouriaux F, Glotin AL, Malecaze F, Faussat AM, Mascarelli F. Extracellular signal-regulated kinase-dependent proliferation is mediated through the protein kinase A/B-Raf pathway in human uveal melanoma cells. J Biol Chem. 2006;281(14):9238–50.

    Article  CAS  PubMed  Google Scholar 

  7. Liu JY, Qian D, He LR, Li YH, Liao YJ, Mai SJ, Tian XP, Liu YH, Zhang JX, Kung HF, Zeng YX, Zhou FJ, Xie D. PinX1 suppresses bladder urothelial carcinoma cell proliferation via the inhibition of telomerase activity and p16/cyclin D1 pathway. Mol Cancer. 2013;12(1):148.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Guo R, Overman M, Chatterjee D, Rashid A, Shroff S, Wang H, Katz MH, Fleming JB, Varadhachary GR, Abbruzzese JL, Wang H. Aberrant expression of p53, p21, cyclin D1, and Bcl2 and their clinicopathological correlation in ampullary adenocarcinoma. Hum Pathol. 2014;45(5):1015–23.

    Article  CAS  PubMed  Google Scholar 

  9. Huang Q, Lan F, Zheng Z, Xie F, Han J, Dong L, Xie Y, Zheng F. Akt2 suppresses GAPDH mediated-apoptosis in ovarian cancer cells via phosphorylating GAPDH at threonine237and decreasing its nuclear translocation. J Biol Chem. 2011;286:42211–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Wang X, Lin Y, Lan F, Yu Y, Ouyang X, Wang X, Huang Q, Wang L, Tan J, Zheng F. A GG allele of 3′-side AKT1 SNP is associated with decreased AKT1 activation and better prognosis of gastric cancer. J Cancer Res Clin Oncol. 2014;140:1399–411.

    Article  CAS  PubMed  Google Scholar 

  11. Wang X, Lin Y, Lan F, Yu Y, Ouyang X, Liu W, Xie F, Wang X. Huang. BAX and CDKN1A polymorphisms correlated with clinical outcomes of gastric cancer patients treated with postoperative chemotherapy. Med Oncol. 2014;31:249.

    Article  CAS  PubMed  Google Scholar 

  12. Kawata N, Tsuchiya N, Horikawa Y, Inoue T, Tsuruta H, Maita S, Satoh S, Mitobe Y, Narita S, Habuchi T. Two survivin polymorphisms are cooperatively associated with bladder cancer susceptibility. Int J Cancer. 2011;129:1872–80.

    Article  CAS  PubMed  Google Scholar 

  13. Pal D, Sur S, Mandal S, Das A, Roy A, Das S, Panda CK. Prevention of liver carcinogenesis by amarogentin through modulation of G1/S cell cycle check point and induction of apoptosis. Carcinogenesis. 2012;33(12):2424–31.

    Article  CAS  PubMed  Google Scholar 

  14. Ju X, Casimiro MC, Gormley M, Meng H, Jiao X, Katiyar S, Crosariol M, Chen K, Wang M, Quong AA, Lisanti MP, Ertel A, Pestell RG. Identification of a cyclin D1 network in prostate cancer that antagonizes epithelial–mesenchymal restraint. Cancer Res. 2014;74(2):508–19.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Xu YY, Wu HJ, Ma HD, Xu LP, Huo Y, Yin LR. MicroRNA-503 suppresses proliferation and cell-cycle progression of endometrioid endometrial cancer by negatively regulating cyclin D1. FEBS J. 2013;280(16):3768–79.

    Article  CAS  PubMed  Google Scholar 

  16. Squires MH 3rd, Fisher SB, Fisher KE, Patel SH, Kooby DA, El-Rayes BF, Staley CA 3rd, Farris AB 3rd, Maithel SK. Differential expression and prognostic value of ERCC1 and thymidylate synthase in resected gastric adenocarcinoma. Cancer. 2013;119(17):3242–50.

    Article  CAS  PubMed  Google Scholar 

  17. Wang MT, Chen G, An SJ, Chen ZH, Huang ZM, Xiao P, Ben XS, Xie Z, Chen SL, Luo DL, Tang JM, Lin JY, Zhang XC, Wu YL. Prognostic significance of cyclinD1 amplification and the co-alteration of cyclinD1/pRb/ppRb in patients with esophageal squamous cell carcinoma. Dis Esophagus. 2012;25(7):664–70.

    Article  PubMed  Google Scholar 

  18. Masuda M, Suzui M, Yasumatu R, Nakashima T, Kuratomi Y, Azuma K, Tomita K, Komiyama S, Weinstein IB. Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res. 2002;62(12):3351–5.

    CAS  PubMed  Google Scholar 

  19. Cai J, Wu J, Zhang H, Fang L, Huang Y, Yang Y, Zhu X, Li R, Li M. miR-186 downregulation correlates with poor survival in lung adenocarcinoma, where it interferes with cell-cycle regulation. Cancer Res. 2013;73(2):756–66.

    Article  CAS  PubMed  Google Scholar 

  20. Umekita Y, Ohi Y, Sagara Y, Yoshida H. Overexpression of cyclinD1 predicts for poor prognosis in estrogen receptor-negative breast cancer patients. Int J Cancer. 2002;8(3):415–8.

    Article  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81372788), the Medical Scientific Research Key Foundation of Nanjing Command (No. 11Z032), and the Natural Science Foundation of Fujian Province Grant (No. 2014J01427) for Qiaojia Huang; The Medical Scientific Innovation Foundation of Nanjing Command (No. MS122) for Yinghao Yu.

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No potential conflicts of interest were declared.

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Correspondence to Qiaojia Huang.

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Liqiang Ma and Xiaoting Wang have contributed equally to this work.

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Ma, L., Wang, X., Lan, F. et al. Prognostic value of differential CCND1 expression in patients with resected gastric adenocarcinoma. Med Oncol 32, 338 (2015). https://doi.org/10.1007/s12032-014-0338-4

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