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HNRNPC as a candidate biomarker for chemoresistance in gastric cancer
Hao Huang1,2, Yong Han1,3, Cheng Zhang1
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
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.
Insights
Chemoresistance in advanced gastric cancer is a challenge. Researchers identified heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) as a key factor, suggesting it could be a prognostic and therapeutic marker for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Chemoresistance significantly contributes to treatment failure and mortality in advanced gastric cancer (AGC).
- The underlying mechanisms of chemoresistance and reliable predictive biomarkers for chemotherapy efficacy in AGC remain largely unknown.
Purpose of the Study:
- To investigate the role of heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC) in chemoresistance of gastric cancer (GC).
- To evaluate HNRNPC as a potential prognostic and therapeutic marker for GC patients.
Main Methods:
- Established 5-fluorouracil (5FU), paclitaxel (TA), and cisplatin (DDP)-resistant human GC cell lines.
- Generated a monoclonal antibody (5B2) targeting overexpressed HNRNPC.
- Utilized small interfering RNA (siRNA) for HNRNPC knockdown.
- Analyzed publicly available datasets to correlate HNRNPC expression with patient survival outcomes.
Main Results:
- HNRNPC was overexpressed in chemoresistant GC cells and its overexpression promoted chemoresistance.
- HNRNPC knockdown reversed chemoresistance in GC cells.
- High HNRNPC transcript levels correlated with poor overall survival (OS) and progression-free survival (FP).
- HNRNPC expression was negatively associated with OS in patients receiving 5FU-based chemotherapy and time to progression (TTP) with the CF regimen.
Conclusions:
- HNRNPC plays a crucial role in promoting chemoresistance in gastric cancer.
- HNRNPC expression levels can serve as a predictive biomarker for chemotherapy response.
- HNRNPC represents a potential prognostic and therapeutic target for advanced gastric cancer.
