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Published on: August 11, 2017
Drug resistance in NSCLC is associated with tumor micro-environment
Weiguo Zhang1, Yizhong Ke1, Xiyu Liu2
1School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
Background:
Tumor cell resistance to chemotherapy is the most critical factor that influences the prognosis of cancer patients. It is generally believed that drug resistance is caused by genetic alterations in tumor cells; however, the relationship between drug resistance and the tumor microenvironment (TME) has not been adequately studied. Herein, we successfully identified drug resistance and sensitivity clusters using single-cell transcriptome sequencing data from GSE149383 and established a proportional hazards model to find genes that affected prognosis. The results showed that marker genes between resistant and sensitive clusters were significantly associated with the TME; additionally, the model showed good reliability. Furthermore, we used bulk RNA-seq data to analyze the expression of CD24 and CYP1B1, which revealed little difference in the levels of the two genes in normal and tumor tissues but a significant difference in their expression between drug-resistant and -sensitive cells. In conclusion, our study demonstrated a link between drug resistance and the TME, and we found that CD24 and CYP1B1 may be key regulators of drug resistance development in tumor cells via altering the TME.
Insights
Chemotherapy resistance in cancer is linked to the tumor microenvironment (TME). This study identifies CD24 and CYP1B1 as key regulators of drug resistance by altering the TME.
Area of Science:
- Oncology
- Cancer Biology
- Genomics
Background:
- Chemotherapy resistance significantly impacts cancer patient prognosis.
- The role of the tumor microenvironment (TME) in drug resistance is understudied.
- Genetic alterations are traditionally considered the primary cause of drug resistance.
Purpose of the Study:
- To investigate the relationship between drug resistance and the TME.
- To identify genes associated with drug resistance and patient prognosis.
- To explore the potential role of CD24 and CYP1B1 in chemotherapy resistance.
Main Methods:
- Single-cell transcriptome sequencing of GSE149383 data to identify resistant and sensitive cell clusters.
- Development of a proportional hazards model to identify prognostic genes.
- Bulk RNA-sequencing analysis to assess CD24 and CYP1B1 expression.
Main Results:
- Distinct drug-resistant and -sensitive cell clusters were identified.
- Marker genes differentiating resistant and sensitive cells were significantly associated with the TME.
- CD24 and CYP1B1 showed minimal difference in normal vs. tumor tissues but significant differences between resistant and sensitive cells.
Conclusions:
- A significant link exists between chemotherapy drug resistance and the TME.
- CD24 and CYP1B1 may be crucial in mediating drug resistance by influencing the TME.
- Targeting CD24 and CYP1B1 could offer new strategies for overcoming chemotherapy resistance.
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