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Mei-Ling Cheng
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-38 - Tumor-Associated Neutrophils as a Potential Predictor for Early Recurrence in Resectable I-IIIA Lung Adenocarcinoma (Now Available) (ID 1509)
10:15 - 18:15 | Author(s): Mei-Ling Cheng
- Abstract
Background
A recurrence of the early-stage non-small cell lung cancer (NSCLC) is usually unpredictable by clinical features alone. It has been appreciated that the high degree of infiltrated neutrophils is significantly associated with poor patient outcome in NSCLC.
Method
Transcriptional profiles and clinical information of 484 primary lung adenocarcinoma (ADC) subjects were retrieved from Gene Expression Omnibus (GEO). An additional cohort of mRNA expression, somatic mutations, and clinical data of 398 ADC were obtained from The Cancer Genome Atlas (TCGA). CIBERSORT algorithm was employed to infer the relative proportions of 22 sorts of leukocytes in each tumor using gene-expression profiles. Patients were stratified into two groups by the fraction of neutrophils using an optimal cutoff value (0.01) obtained with the "survminer" algorithm in R. We further investigated comprehensively the molecular differences between the high- and low-neutrophils patients.
Result
A significantly higher rate of 1-year recurrence was found in the high-neutrophils compared with the low-neutrophils group in both training (GEO,19.5% vs 6.1%) and validation (TCGA, 27.3% vs 19.0%) cohorts. However only in training cohort the patients with high neutrophils experienced a poorer recurrence-free survival (HR 1.95, 95% CI 1.47-2.51, P< 0.0001). The two groups were not only distinguished by clinical behaviors, but presented characteristic mutation genes and mutation patterns. EGFR and BRAF were more frequently mutated in low-neutrophils patients, whereas in high-neutrophils patients the most common mutation was found in STK11. Yet such molecular distinction was more pronounced in ADC with high tumor mutation load (TMB >=10). Gene Set Enrichment Analysis (GSEA) suggested that the common mutant genes in high-neutrophils patients were involved in the TP53 signaling, cell cycle pathways or associated with molecular functions including chemokine production and CD4 activation, while the common mutant genes in low-neutrophils patients were linked to RAS signaling pathway. Interestingly, we observed immune scene accompanied with good prognosis of ADC and concordant with limited infiltration of neutrophils, for instance high infiltration of B memory cells, resting memory CD4+T cells, resting mast cells and CD8+T cells.
Conclusion
Our findings suggested that local neutrophils are one of important components which are determinant for early recurrence of ADC, and it might serve as a simple predictor. Further research is warranted to identify the molecular mechanisms that neutrophils employed to exert, directly or indirectly, the regulatory effect on ADC progression.
