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Published in: Tumor Biology 3/2016

01-03-2016 | Original Article

HNRNPC as a candidate biomarker for chemoresistance in gastric cancer

Authors: Hao Huang, Yong Han, Cheng Zhang, Jian Wu, Junnan Feng, Like Qu, Chengchao Shou

Published in: Tumor Biology | Issue 3/2016

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Abstract

Chemoresistance is a major cause of treatment failure and high mortality in advanced gastric cancer (AGC). Currently, the mechanism of chemoresistance remains unclear, and there is no biomarker to accurately predict the efficacy of chemotherapy. In the present study, we established human gastric cancer (GC) cell lines resistant to 5-fluorouracil (5FU), paclitaxel (TA), or cisplatin (DDP) by gradient drug treatment and generated a novel monoclonal antibody 5B2 targeting heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) overexpressed in chemoresistant GC cells. Overexpressing HNRNPC in GC cells promoted chemoresistance, and knockdown of HNRNPC by small interfering RNA (siRNA) reversed chemoresistance. By utilizing available datasets, we demonstrated that high level of HNRNPC transcript indicated poor overall survival (OS) and free of progression (FP). HNRNPC expression was negatively correlated with OS of GC patients treated with 5FU-based drugs and with time to progression (TTP) of GC patients treated with CF regimen. These data suggest the potential usefulness of HNRNPC as a prognostic and therapeutic marker of GC.
Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.CrossRefPubMed
2.
go back to reference Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidem Biomar. 2014;23(5):700–13. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidem Biomar. 2014;23(5):700–13.
3.
go back to reference Lustosa SA, Saconato H, Atallah AN, Lopes Filho Gde J, Matos D. Impact of extended lymphadenectomy on morbidity, mortality, recurrence and 5-year survival after gastrectomy for cancer. Meta-analysis of randomized clinical trials. Acta Cir Bras. 2008;23(6):520–30. Lustosa SA, Saconato H, Atallah AN, Lopes Filho Gde J, Matos D. Impact of extended lymphadenectomy on morbidity, mortality, recurrence and 5-year survival after gastrectomy for cancer. Meta-analysis of randomized clinical trials. Acta Cir Bras. 2008;23(6):520–30.
4.
go back to reference Garrido M, Fonseca PJ, Vieitez JM, Frunza M, Lacave AJ. Challenges in first line chemotherapy and targeted therapy in advanced gastric cancer. Expert Rev Anticancer Ther. 2014;14(8):887–900.CrossRefPubMed Garrido M, Fonseca PJ, Vieitez JM, Frunza M, Lacave AJ. Challenges in first line chemotherapy and targeted therapy in advanced gastric cancer. Expert Rev Anticancer Ther. 2014;14(8):887–900.CrossRefPubMed
6.
go back to reference Wong R, Cunningham D. Optimising treatment regimens for the management of advanced gastric cancer. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2009;20(4):605–8.CrossRef Wong R, Cunningham D. Optimising treatment regimens for the management of advanced gastric cancer. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2009;20(4):605–8.CrossRef
7.
go back to reference Geng R, Li J. Apatinib for the treatment of gastric cancer. Expert Opin Pharmacother. 2015;16(1):117–22.CrossRefPubMed Geng R, Li J. Apatinib for the treatment of gastric cancer. Expert Opin Pharmacother. 2015;16(1):117–22.CrossRefPubMed
8.
go back to reference Zheng L, Tan W, Zhang J, Yuan D, Yang J, Liu H. Combining trastuzumab and cetuximab combats trastuzumab-resistant gastric cancer by effective inhibition of EGFR/ErbB2 heterodimerization and signaling. Cancer Immunol Immunother CII. 2014;63(6):581–6.CrossRefPubMed Zheng L, Tan W, Zhang J, Yuan D, Yang J, Liu H. Combining trastuzumab and cetuximab combats trastuzumab-resistant gastric cancer by effective inhibition of EGFR/ErbB2 heterodimerization and signaling. Cancer Immunol Immunother CII. 2014;63(6):581–6.CrossRefPubMed
9.
go back to reference Zhang D, Fan D. New insights into the mechanisms of gastric cancer multidrug resistance and future perspectives. Future Oncol. 2010;6(4):527–37.CrossRefPubMed Zhang D, Fan D. New insights into the mechanisms of gastric cancer multidrug resistance and future perspectives. Future Oncol. 2010;6(4):527–37.CrossRefPubMed
10.
go back to reference Krueger P, Nitz C, Foster R, MacDonald C, Gelber O, Lalehzadeh G, et al. A new small cell lung cancer (SCLC)-specific marker discovered through antigenic subtraction of neuroblastoma cells. Cancer Immunol Immunother CII. 2003;52(6):367–77.PubMed Krueger P, Nitz C, Foster R, MacDonald C, Gelber O, Lalehzadeh G, et al. A new small cell lung cancer (SCLC)-specific marker discovered through antigenic subtraction of neuroblastoma cells. Cancer Immunol Immunother CII. 2003;52(6):367–77.PubMed
11.
go back to reference Mattes MJ, Look K, Furukawa K, Pierce VK, Old LJ, Lewis Jr JL, et al. Mouse monoclonal antibodies to human epithelial differentiation antigens expressed on the surface of ovarian carcinoma ascites cells. Cancer Res. 1987;47(24 Pt 1):6741–50.PubMed Mattes MJ, Look K, Furukawa K, Pierce VK, Old LJ, Lewis Jr JL, et al. Mouse monoclonal antibodies to human epithelial differentiation antigens expressed on the surface of ovarian carcinoma ascites cells. Cancer Res. 1987;47(24 Pt 1):6741–50.PubMed
12.
go back to reference Yin BW, Kiyamova R, Chua R, Caballero OL, Gout I, Gryshkova V, et al. Monoclonal antibody MX35 detects the membrane transporter NaPi2b (SLC34A2) in human carcinomas. Cancer Immun. 2008;8:3.PubMedPubMedCentral Yin BW, Kiyamova R, Chua R, Caballero OL, Gout I, Gryshkova V, et al. Monoclonal antibody MX35 detects the membrane transporter NaPi2b (SLC34A2) in human carcinomas. Cancer Immun. 2008;8:3.PubMedPubMedCentral
13.
go back to reference Zhao W, Wang L, Han H, Jin K, Lin N, Guo T, et al. 1B50-1, a mAb raised against recurrent tumor cells, targets liver tumor-initiating cells by binding to the calcium channel alpha2delta1 subunit. Cancer Cell. 2013;23(4):541–56.CrossRefPubMed Zhao W, Wang L, Han H, Jin K, Lin N, Guo T, et al. 1B50-1, a mAb raised against recurrent tumor cells, targets liver tumor-initiating cells by binding to the calcium channel alpha2delta1 subunit. Cancer Cell. 2013;23(4):541–56.CrossRefPubMed
14.
go back to reference Harris M. Monoclonal antibodies as therapeutic agents for cancer. Lancet Oncol. 2004;5(5):292–302.CrossRefPubMed Harris M. Monoclonal antibodies as therapeutic agents for cancer. Lancet Oncol. 2004;5(5):292–302.CrossRefPubMed
15.
16.
go back to reference Szoke D, Gyorffy A, Surowiak P, Tulassay Z, Dietel M, Gyorffy B. Identification of consensus genes and key regulatory elements in 5-fluorouracil resistance in gastric and colon cancer. Onkologie. 2007;30(8–9):421–6.PubMed Szoke D, Gyorffy A, Surowiak P, Tulassay Z, Dietel M, Gyorffy B. Identification of consensus genes and key regulatory elements in 5-fluorouracil resistance in gastric and colon cancer. Onkologie. 2007;30(8–9):421–6.PubMed
17.
go back to reference Kim HK, Choi IJ, Kim CG, Kim HS, Oshima A, Michalowski A, et al. A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients. PLoS One. 2011;6(2):e16694.CrossRefPubMedPubMedCentral Kim HK, Choi IJ, Kim CG, Kim HS, Oshima A, Michalowski A, et al. A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients. PLoS One. 2011;6(2):e16694.CrossRefPubMedPubMedCentral
19.
go back to reference Shekhar MP. Drug resistance: challenges to effective therapy. Curr Cancer Drug Targets. 2011;11(5):613–23.CrossRefPubMed Shekhar MP. Drug resistance: challenges to effective therapy. Curr Cancer Drug Targets. 2011;11(5):613–23.CrossRefPubMed
20.
go back to reference Xu HW, Xu L, Hao JH, Qin CY, Liu H. Expression of P-glycoprotein and multidrug resistance-associated protein is associated with multidrug resistance in gastric cancer. J Int Med Res. 2010;38(1):34–42.CrossRefPubMed Xu HW, Xu L, Hao JH, Qin CY, Liu H. Expression of P-glycoprotein and multidrug resistance-associated protein is associated with multidrug resistance in gastric cancer. J Int Med Res. 2010;38(1):34–42.CrossRefPubMed
21.
go back to reference Cascinu S, Graziano F, Del Ferro E, Staccioli MP, Ligi M, Carnevali A, et al. Expression of p53 protein and resistance to preoperative chemotherapy in locally advanced gastric carcinoma. Cancer. 1998;83(9):1917–22.CrossRefPubMed Cascinu S, Graziano F, Del Ferro E, Staccioli MP, Ligi M, Carnevali A, et al. Expression of p53 protein and resistance to preoperative chemotherapy in locally advanced gastric carcinoma. Cancer. 1998;83(9):1917–22.CrossRefPubMed
22.
go back to reference Matsuhashi N, Saio M, Matsuo A, Sugiyama Y, Saji S. The evaluation of gastric cancer sensitivity to 5-FU/CDDP in terms of induction of apoptosis: time- and p53 expression-dependency of anti-cancer drugs. Oncol Rep. 2005;14(3):609–15.PubMed Matsuhashi N, Saio M, Matsuo A, Sugiyama Y, Saji S. The evaluation of gastric cancer sensitivity to 5-FU/CDDP in terms of induction of apoptosis: time- and p53 expression-dependency of anti-cancer drugs. Oncol Rep. 2005;14(3):609–15.PubMed
23.
go back to reference Shen XM, Zhou C, Lian L, Li LQ, Li W, Tao M. Relationship Between the DPD and TS mRNA Expression and the Response to S-1-Based Chemotherapy and Prognosis in Patients with Advanced Gastric Cancer. Cell Biochem Biophys. 2014. Shen XM, Zhou C, Lian L, Li LQ, Li W, Tao M. Relationship Between the DPD and TS mRNA Expression and the Response to S-1-Based Chemotherapy and Prognosis in Patients with Advanced Gastric Cancer. Cell Biochem Biophys. 2014.
24.
go back to reference Canadas I, Rojo F, Taus A, Arpi O, Arumi-Uria M, Pijuan L, et al. Targeting epithelial-to-mesenchymal transition with Met inhibitors reverts chemoresistance in small cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2014;20(4):938–50.CrossRef Canadas I, Rojo F, Taus A, Arpi O, Arumi-Uria M, Pijuan L, et al. Targeting epithelial-to-mesenchymal transition with Met inhibitors reverts chemoresistance in small cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2014;20(4):938–50.CrossRef
25.
go back to reference Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5(4):275–84.CrossRefPubMed Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer. 2005;5(4):275–84.CrossRefPubMed
26.
go back to reference Yoon JH, Ahn SG, Lee BH, Jung SH, Oh SH. Role of autophagy in chemoresistance: regulation of the ATM-mediated DNA-damage signaling pathway through activation of DNA-PKcs and PARP-1. Biochem Pharmacol. 2012;83(6):747–57.CrossRefPubMed Yoon JH, Ahn SG, Lee BH, Jung SH, Oh SH. Role of autophagy in chemoresistance: regulation of the ATM-mediated DNA-damage signaling pathway through activation of DNA-PKcs and PARP-1. Biochem Pharmacol. 2012;83(6):747–57.CrossRefPubMed
27.
go back to reference Yang Y, Li H, Hou S, Hu B, Liu J, Wang J. The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell. PLoS One. 2013;8(5):e65309.CrossRefPubMedPubMedCentral Yang Y, Li H, Hou S, Hu B, Liu J, Wang J. The noncoding RNA expression profile and the effect of lncRNA AK126698 on cisplatin resistance in non-small-cell lung cancer cell. PLoS One. 2013;8(5):e65309.CrossRefPubMedPubMedCentral
28.
go back to reference Burd CG, Swanson MS, Gorlach M, Dreyfuss G. Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts. Proc Natl Acad Sci U S A. 1989;86(24):9788–92.CrossRefPubMedPubMedCentral Burd CG, Swanson MS, Gorlach M, Dreyfuss G. Primary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts. Proc Natl Acad Sci U S A. 1989;86(24):9788–92.CrossRefPubMedPubMedCentral
29.
go back to reference Liang CR, Leow CK, Neo JC, Tan GS, Lo SL, Lim JW, et al. Proteome analysis of human hepatocellular carcinoma tissues by two-dimensional difference gel electrophoresis and mass spectrometry. Proteomics. 2005;5(8):2258–71.CrossRefPubMed Liang CR, Leow CK, Neo JC, Tan GS, Lo SL, Lim JW, et al. Proteome analysis of human hepatocellular carcinoma tissues by two-dimensional difference gel electrophoresis and mass spectrometry. Proteomics. 2005;5(8):2258–71.CrossRefPubMed
30.
go back to reference Rajagopalan LE, Westmark CJ, Jarzembowski JA, Malter JS. hnRNP C increases amyloid precursor protein (APP) production by stabilizing APP mRNA. Nucleic Acids Res. 1998;26(14):3418–23.CrossRefPubMedPubMedCentral Rajagopalan LE, Westmark CJ, Jarzembowski JA, Malter JS. hnRNP C increases amyloid precursor protein (APP) production by stabilizing APP mRNA. Nucleic Acids Res. 1998;26(14):3418–23.CrossRefPubMedPubMedCentral
31.
go back to reference Lee SY, Park JH, Kim S, Park EJ, Yun Y, Kwon J. A proteomics approach for the identification of nucleophosmin and heterogeneous nuclear ribonucleoprotein C1/C2 as chromatin-binding proteins in response to DNA double-strand breaks. Biochem J. 2005;388(Pt 1):7–15.CrossRefPubMedPubMedCentral Lee SY, Park JH, Kim S, Park EJ, Yun Y, Kwon J. A proteomics approach for the identification of nucleophosmin and heterogeneous nuclear ribonucleoprotein C1/C2 as chromatin-binding proteins in response to DNA double-strand breaks. Biochem J. 2005;388(Pt 1):7–15.CrossRefPubMedPubMedCentral
32.
go back to reference Christian KJ, Lang MA, Raffalli-Mathieu F. Interaction of heterogeneous nuclear ribonucleoprotein C1/C2 with a novel cis-regulatory element within p53 mRNA as a response to cytostatic drug treatment. Mol Pharmacol. 2008;73(5):1558–67.CrossRefPubMed Christian KJ, Lang MA, Raffalli-Mathieu F. Interaction of heterogeneous nuclear ribonucleoprotein C1/C2 with a novel cis-regulatory element within p53 mRNA as a response to cytostatic drug treatment. Mol Pharmacol. 2008;73(5):1558–67.CrossRefPubMed
33.
go back to reference Blume SW, Jackson NL, Frost AR, Grizzle WE, Shcherbakov OD, Choi H, et al. Northwestern profiling of potential translation-regulatory proteins in human breast epithelial cells and malignant breast tissues: evidence for pathological activation of the IGF1R IRES. Exp Mol Pathol. 2010;88(3):341–52.CrossRefPubMedPubMedCentral Blume SW, Jackson NL, Frost AR, Grizzle WE, Shcherbakov OD, Choi H, et al. Northwestern profiling of potential translation-regulatory proteins in human breast epithelial cells and malignant breast tissues: evidence for pathological activation of the IGF1R IRES. Exp Mol Pathol. 2010;88(3):341–52.CrossRefPubMedPubMedCentral
34.
go back to reference Sell C, Rubini M, Rubin R, Liu JP, Efstratiadis A, Baserga R. Simian virus 40 large tumor antigen is unable to transform mouse embryonic fibroblasts lacking type 1 insulin-like growth factor receptor. Proc Natl Acad Sci U S A. 1993;90(23):11217–21.CrossRefPubMedPubMedCentral Sell C, Rubini M, Rubin R, Liu JP, Efstratiadis A, Baserga R. Simian virus 40 large tumor antigen is unable to transform mouse embryonic fibroblasts lacking type 1 insulin-like growth factor receptor. Proc Natl Acad Sci U S A. 1993;90(23):11217–21.CrossRefPubMedPubMedCentral
35.
go back to reference Park YM, Hwang SJ, Masuda K, Choi KM, Jeong MR, Nam DH, et al. Heterogeneous nuclear ribonucleoprotein C1/C2 controls the metastatic potential of glioblastoma by regulating PDCD4. Mol Cell Biol. 2012;32(20):4237–44.CrossRefPubMedPubMedCentral Park YM, Hwang SJ, Masuda K, Choi KM, Jeong MR, Nam DH, et al. Heterogeneous nuclear ribonucleoprotein C1/C2 controls the metastatic potential of glioblastoma by regulating PDCD4. Mol Cell Biol. 2012;32(20):4237–44.CrossRefPubMedPubMedCentral
Metadata
Title
HNRNPC as a candidate biomarker for chemoresistance in gastric cancer
Authors
Hao Huang
Yong Han
Cheng Zhang
Jian Wu
Junnan Feng
Like Qu
Chengchao Shou
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4144-1

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