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Published on: February 12, 2017
THSD7B Mutation Induces Platinum Resistance in Small Cell Lung Cancer Patients
Zifu Yao1,2, Anqi Lin1, Yonglin Yi1
1Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China.
Aim:
Several cases of small cell lung cancer (SCLC) patients demonstrate resistance to the treatment initiatives such as cisplatin after platinum chemotherapy. It is crucial to the improvement of the overall survival (OS) of SCLC patients to discover the gene mutation inducing platinum resistance within this cohort.
Patients And Methods:
We analyzed the gene mutations significantly associated with the OS from 2 cohorts of SCLC platinum-treated patients. And then we screened out THSD7B mutation. In order to understand the mechanism between THSD7B mutation and platinum resistance, we designed gene mutation co-occurrence and mutual exclusivity analysis, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) analysis, and Connectivity Map (CMap) analysis.
Results:
The poor prognosis of THSD7B mutant patients may be related to the inhibition of cell death-related pathways, the up-regulation of cell invasion and metastasis pathways, and the down-regulation of immune response pathways. Lovastatin and cyclooxygenase inhibitors could be used as potential target compounds in THSD7B mutant patients, which provides reference for future research on platinum resistance.
Conclusion:
THSD7B can be considered a reliable biomarker that effectively facilitates the prediction of poor survival in SCLC platinum-treated patients.
Insights
THSD7B gene mutations are linked to platinum resistance in small cell lung cancer (SCLC) patients, indicating poor survival. This finding may guide future SCLC treatment strategies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Small cell lung cancer (SCLC) patients often develop resistance to platinum-based chemotherapy.
- Identifying the genetic drivers of platinum resistance is crucial for improving overall survival (OS) in SCLC.
Purpose of the Study:
- To identify gene mutations associated with platinum resistance in SCLC.
- To elucidate the mechanism by which THSD7B mutations contribute to platinum resistance.
Main Methods:
- Analysis of gene mutations in two cohorts of SCLC patients treated with platinum chemotherapy.
- Utilized gene mutation co-occurrence/exclusivity analysis, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and Connectivity Map (CMap) analysis.
Main Results:
- THSD7B mutation was identified as significantly associated with OS in SCLC patients.
- THSD7B mutations may lead to poor prognosis by inhibiting cell death, promoting invasion/metastasis, and downregulating immune responses.
- Lovastatin and cyclooxygenase inhibitors show potential as therapeutic agents for THSD7B mutant SCLC.
Conclusions:
- THSD7B serves as a reliable biomarker for predicting poor survival in SCLC patients undergoing platinum chemotherapy.
- Understanding THSD7B's role in platinum resistance offers new avenues for targeted SCLC therapies.
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