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Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
Expression and mutation of the c-kit gene and correlation with prognosis of small cell lung cancer
Hong-Yang Lu1, Gu Zhang, Qiao-Yuan Cheng
1Zhejiang Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology (esophagus, lung), Zhejiang Province.
Abstract:
Small cell lung cancer (SCLC) is a highly aggressive and lethal type of cancer in humans. SCLC is sensitive to chemotherapy and radiotherapy, but long-term survival is low and the majority of patients eventually develop progressive disease. With the success of imatinib mesylate in the treatment of gastrointestinal stromal tumors expressing c-kit, its use in SCLC serves as a novel molecular therapeutic approach. The activity of imatinib mesylate is correlated with the mutation of c-kit gene exons 9 and 11 in gastrointestinal stromal tumors. The incidence of epidermal growth factor receptor mutation in non-small cell lung cancer is higher in China than in the United States of America and European countries. There may be also differences in the incidence of c-kit mutation between China and European countries. At present, no study examining imatinib mesylate treatment for SCLC in China is available. To investigate the expression and mutation of c-kit and the correlation with prognosis of SCLC in China, immunohistochemistry was used to detect the expression of c-kit, and a pyrosequencing assay was used to detect mutations in c-kit exons 9 and 11 of 36 SCLC patients who received surgical treatment at the Zhejiang Cancer Hospital, Hangzhou, China, between 1998 and 2010. All 36 patients were followed up to analyze the correlation between prognosis and expression and mutation of c-kit. The incidence of c-kit-positive expression was 83.3%, including 25.0% weak staining, 22.2% moderate staining and 36.1% strong staining. The overall survival of patients with c-kit strong staining was shorter compared to patients with c-kit not strong staining. No mutation in c-kit exons 9 and 11 was detected. In conclusion, the findings showed that the expression of c-kit is high, and strong staining is a prognostic factor for worse survival.
Insights
Small cell lung cancer (SCLC) exhibits high c-kit expression in China. Strong c-kit staining, but not mutations, is linked to poorer survival, suggesting a potential prognostic marker for SCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Small cell lung cancer (SCLC) is an aggressive malignancy with poor long-term survival rates.
- Targeted therapies like imatinib mesylate show promise, but their efficacy in SCLC, particularly in China, requires investigation.
- Understanding c-kit expression and mutation in SCLC is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the expression and mutation status of the c-kit gene in Chinese SCLC patients.
- To determine the correlation between c-kit expression/mutation and the prognosis of SCLC.
- To evaluate the potential of c-kit as a therapeutic target or prognostic biomarker in SCLC.
Main Methods:
- Immunohistochemistry was employed to assess c-kit protein expression in 36 SCLC patient samples.
- Pyrosequencing assays were utilized to detect mutations in c-kit exons 9 and 11.
- Patient survival data was analyzed to correlate c-kit status with prognosis.
Main Results:
- High incidence of c-kit positive expression (83.3%) was observed in SCLC patients.
- Strong c-kit staining was associated with significantly shorter overall survival.
- No mutations were detected in c-kit exons 9 and 11.
Conclusions:
- The expression of c-kit is prevalent in Chinese SCLC patients.
- Strong c-kit staining serves as a negative prognostic factor for SCLC survival.
- Targeting c-kit may not be effective due to the absence of mutations, but its expression level is a significant prognostic indicator.
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