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.
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Acknowledgments
We deeply appreciate Dr. Györffy (Semmelweis University, Budapest, Hungary) and Dr. Green JE (Transgenic Oncogenesis and Genomics Section, Center for Cancer Research, National Cancer Institute) for providing gene expression datasets of gastric cancer patients. This study was supported by National Basic Research Program of China (2015CB553906).
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Hao Huang and Yong Han contributed equally to this work.
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Huang, H., Han, Y., Zhang, C. et al. HNRNPC as a candidate biomarker for chemoresistance in gastric cancer. Tumor Biol. 37, 3527–3534 (2016). https://doi.org/10.1007/s13277-015-4144-1
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DOI: https://doi.org/10.1007/s13277-015-4144-1