ABCC3 as a marker for multidrug resistance in non-small cell lung cancer
Yanbin Zhao1, Hailing Lu, An Yan
11] Department of Internal Medical Oncology, the Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China [2].
Abstract:
Multidrug resistance (MDR) contributes to the failure of chemotherapy and high mortality in non-small cell lung cancer (NSCLC). We aim to identify MDR genes that predict tumor response to chemotherapy. 199 NSCLC fresh tissue samples were tested for chemosensitivity by MTT assay. cDNA microarray was done with 5 samples with highest resistance and 6 samples with highest sensitivity. Expression of ABCC3 mRNA and protein was detected by real-time PCR and immunohistochemisty, respectively. The association between gene expression and overall survival (OS) was examined using Cox proportional hazard regression. 44 genes were upregulated and 168 downregulated in the chemotherapy-resistant group. ABCC3 was one of the most up-regulated genes in the resistant group. ABCC3-positive expression correlated with lymph node involvement, advanced TNM stage, more malignant histological type, multiple-resistance to anti-cancer drugs, and reduced OS. ABCC3 expression may serve as a marker for MDR and predictor for poor clinical outcome of NSCLC.
Insights
Multidrug resistance (MDR) in non-small cell lung cancer (NSCLC) is a major challenge. The study found that ABCC3 gene expression predicts poor outcomes and chemotherapy resistance in NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multidrug resistance (MDR) significantly impacts chemotherapy efficacy and survival rates in non-small cell lung cancer (NSCLC).
- Identifying reliable biomarkers for MDR is crucial for predicting treatment response and patient outcomes.
Purpose of the Study:
- To identify genes associated with multidrug resistance in NSCLC.
- To evaluate the potential of ABCC3 as a predictive marker for chemotherapy response and clinical outcome in NSCLC.
Main Methods:
- Chemosensitivity testing using MTT assay on 199 NSCLC samples.
- cDNA microarray analysis comparing resistant and sensitive NSCLC tissues.
- Real-time PCR and immunohistochemistry to assess ABCC3 mRNA and protein expression.
- Cox proportional hazard regression to analyze the association between gene expression and overall survival (OS).
Main Results:
- 44 genes were upregulated and 168 downregulated in chemotherapy-resistant NSCLC samples.
- ABCC3 was identified as a significantly upregulated gene in the resistant group.
- ABCC3-positive expression correlated with lymph node involvement, advanced TNM stage, aggressive histology, multiple drug resistance, and reduced OS.
Conclusions:
- ABCC3 expression is associated with multidrug resistance in NSCLC.
- ABCC3 may serve as a valuable biomarker for predicting poor clinical outcomes and chemotherapy resistance in NSCLC patients.
