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Published on: February 12, 2017
mRNA Network: Solution for Tracking Chemotherapy Insensitivity in Small-Cell Lung Cancer
Peixin Chen1,2, Shengyu Wu1,2, Jia Yu1,2
1Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.
Background:
Small-cell lung cancer (SCLC) has poor prognosis and is prone to drug resistance. It is necessary to search for possible influencing factors for SCLC chemotherapy insensitivity. Therefore, we proposed an mRNA network to track the chemotherapy insensitivity in SCLC.
Methods:
Six samples of patients with SCLC were recruited for RNA sequencing. TopHat2 and Cufflinks were used to make differential analysis. Functional analysis was applied as well. Finally, multidimensional validation was applied for verifying the results we obtained by experiment.
Results:
This study was a trial of drug resistance in 6 SCLC patients after first-line chemotherapy. The top 10 downregulated genes differentially expressed in the chemo-insensitive group were SERPING1, DRD5, PARVG, PRAME, NKX1-1, MCTP2, PID1, PLEKHA4, SPP1, and SLN. Cell-cell signaling by Wnt (p=6.98E - 21) was the most significantly enriched GO term in biological process, while systemic lupus erythematosus (p=6.97E - 10), alcoholism (p=1.01E - 09), and transcriptional misregulation in cancer (p=0.00227988) were the top three ones of KEGG pathways. In multiple public databases, we also highlighted and verified the vital role of glycolysis/gluconeogenesis pathway and corresponding genes in chemo-insensitivity in SCLC.
Conclusion:
Our study confirmed some SCLC chemotherapy insensitivity-related genes, biological processes, and pathways, thus constructing the chemotherapy-insensitive network for SCLC.
Insights
This study identifies key genes and pathways linked to chemotherapy insensitivity in small-cell lung cancer (SCLC). The findings help build an mRNA network to understand and potentially overcome drug resistance in SCLC patients.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Small-cell lung cancer (SCLC) presents a significant clinical challenge due to its poor prognosis and propensity for developing drug resistance.
- Identifying factors that influence chemotherapy insensitivity is crucial for improving treatment outcomes in SCLC.
Purpose of the Study:
- To investigate the molecular mechanisms underlying chemotherapy insensitivity in SCLC.
- To develop an mRNA network for tracking chemotherapy insensitivity in SCLC.
Main Methods:
- RNA sequencing was performed on six SCLC patient samples.
- Differential gene expression analysis was conducted using TopHat2 and Cufflinks.
- Functional enrichment analysis (GO and KEGG) and multidimensional validation were employed.
Main Results:
- Ten downregulated genes, including SERPING1, DRD5, and PRAME, were identified in the chemo-insensitive group.
- Enriched pathways included Wnt signaling, systemic lupus erythematosus, alcoholism, and transcriptional misregulation in cancer.
- The glycolysis/gluconeogenesis pathway and its associated genes were validated as critical in SCLC chemo-insensitivity.
Conclusions:
- This research confirms specific genes, biological processes, and pathways associated with SCLC chemotherapy insensitivity.
- An mRNA network was constructed to better understand and target chemotherapy resistance in SCLC.
