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Qiang Nie
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FP01 - Early Stage/Localized Disease (ID 111)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP01.03 - Genetic Predisposition for Pre-Invasive Lung Adenocarcinoma Manifesting as Ground-Glass Nodules with Family History of Lung Cancer (ID 1512)
00:00 - 00:00 | Author(s): Qiang Nie
- Abstract
Introduction
Lung cancer with family history have been increasing gradually of late years in East Asian, especially those presenting as pulmonary ground-glass nodules (GGNs). The predisposition of GGN with lung cancer family history remains baffling.
Methods
This prospective study (NCT04220268) enrolled patients with pulmonary pre-invasive or invasive adenocarcinoma, which presenting as GGN in computer tomography (CT) scans. We used extreme phenotype approach to select 50 GGN patients with a family history of lung cancer (FHLC) in one or more first-degree relatives. Blood samples were collected and sequenced by whole exome sequencing (WES) to investigate rare but potential pathogenic germline mutations with a stepwise filtering strategy including: variant quality and classification, minor allele frequency (MAF) < 0.01 in public and local database, functional prediction and family segregation.
Results
In total, 2325 single nucleotide variants (SNVs) and 238 frameshift mutations with MAF <0.01 were finally identified through the filter. The number of these rare, damaging germline mutations in non-smoking patients were significantly higher than those in smoking patients (Spearman’s ρ= -0.33, p=0.02). Fifty-nine SNVs and 10 frameshifts were not only rare and deleterious but also presented in more than two families. Importantly, twenty of them had been reported to be associated with higher risk or carcinogenesis of lung cancer. Two of them were validated in 126 nonoverlapping susceptibility loci for lung carcinogenesis identified by genome-wide association studies (GWAS).
Conclusion
Patients with GGNs and FHLC may have inheritable carcinogenesis mutations. These variants may potentially contribute to the risk of pulmonary pre-invasive adenocarcinoma susceptibility in Chinese population. Non-smoking patients with GGN probably had higher genetic predisposition than the smoking patients.
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MA13 - Tumor Biology: Focus on EGFR Mutation, DNA Repair and Tumor Microenvironment (ID 214)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/31/2021, 16:45 - 17:45, Scientific Program Auditorium
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MA13.09 - Heterogeneous Genomic Evolution and Immune Microenvironments in Metastatic Lung Cancer (ID 1155)
16:45 - 17:45 | Author(s): Qiang Nie
- Abstract
Introduction
The comprehensive insights into the genomic evolution and immune microenvironments of lung cancer metastasis remain unknown. Furthermore, whether non-stochastic patterns of lung cancer metastases to different sites exist is elusive.
Methods
We investigated the genomic evolution and immune microenvironments of paired primary-metastatic (P-M) tumors by employing multi-region whole-exome sequencing and immunohistochemistry in 179 samples from 51 lung cancer patients with metastases to the pleura, bone, adrenal gland, brain and additional lymph nodes.
Results
Our data revealed differences in genomic landscapes, molecular determinants, seeding patterns, and lymphocyte infiltration among different metastatic sites. Metastatic lymph nodes showed the highest P-M genomic divergence, followed by pleura, brain, bone, and adrenal gland. We identified MYC amplification as a selected event driving metastasis and associated with worse overall survival (P = 0.013). Interestingly, EGFR amplification and TP53 mutations were preferably selected in distant metastases whereas RICTOR amplification was selected in regional metastases (pleura and lymph nodes). Based on spatial tumor growth model, we demonstrated commonly late arising of metastatic seeding (61.1%) of lung cancer with quantitative evidence. However, mutation rate and timing of dissemination varied among different metastatic sites. Metastases at regional tissues were more frequently infiltrated with CD8+ tumor-infiltrating lymphocytes (TILs) than those at distant organs, among which bone metastases were merely infiltrated with CD8+ TILs. Furthermore, monoclonal and polyclonal seeding were associated with rapid and attenuated progression (P = 0.013), respectively, which supports the potential value as a prognostic predictor. Immune-heterogeneity and -homogeneity were primarily driven by arm-level and focal copy number events in primary tumors, respectively, indicating distinct mechanisms of tumor immune escape during metastasis.
Conclusion
These findings implied the combinatorial role of multiple factors in shaping patterns of dissemination and advanced the clinical evaluation and intervention of lung cancer metastasis.
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P56 - Tumor Biology and Systems Biology - Basic and Translational Science - CT DNA (ID 193)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P56.01 - Postoperative ctDNA Positive Presents the High-risk of Recurrence in Resectable Non-Small Cell Lung Cancers (ID 1436)
00:00 - 00:00 | Author(s): Qiang Nie
- Abstract
Introduction
Effective biomarkers to predict the prognosis for non-small cell lung cancer (NSCLC) patients after radical resection are needed. As a potential novel maker, ctDNA help to determine which patients harbor residual disease after surgery. Here, we analyze the significance of postoperative ctDNA in this prospective cohort.
Methods
Twenty-six NSCLC surgical patients were enrolled. The paired surgical tissues and postoperative peripheral blood samples were collected. Using hybridization capture-based NGS ER-seq method, 1021-gene panel for 26 tissues and 293-gene panel for 30 ctDNA samples, which enables simultaneously assess snv/indel, cnv and rearrangement variation.
Results
Median age was 61 years (range 33-78), 9 had smoking history, and 17 were males. There were 16 lung adenocarcinoma, 6 lung squamous carcinoma, 2 sarcomatoid carcinoma, 1 adenosquamous carcinoma and 1 lymphoepithelioma-like carcinoma. Four were stage Ⅰ, 10 stage Ⅱ and 12 stage Ⅲ. Thirteen patients received adjuvant therapy.
In tissue samples, TP53 was the most common driver gene (65.4%). Followed by EGFR (30.8%), APC (19.2%), KRAS (11.5%), et. The median mutation number was 8.5 (from 3-50), and median TMB was 6.9muts/Mb (range 1-48). The mutation number had no relationship with ctDNA status. Postoperative ctDNA positive was found in 5 of 26 patients (19.2%), 3 stage Ⅲ and 2 stage Ⅱ, with a total of 10 mutations, range from 1 to 6 per-sample. The median highest mutant allele frequency (hMAF) per-sample was 0.1% (range 0.07%-6.6%). Two (7.7%) patients had actionable mutation in ctDNA.
The median follow-up time was 10 months (range 3.5-18). Only 5 (5/21, 23.8%) patients in ctDNA negative group had disease recrruence, but patients in ctDNA positive group were all relapsed (P=0.004). The disease-free survival (DFS) was significantly shorter in ctDNA positive group than ctDNA negative (mDFS 7.4 vs 16.9 mos, P﹤0.0001; HR, 9.455; 95% CI, 1.149 to 77.78). Among 12 stage Ⅲ patents, shorter DFS was also observed in ctDNA positive patients than negative (P=0.0017; HR, 7.032).
There were three patients had ctDNA monitoring results. Two persistently ctDNA negative cases did not relapse. But the patient with ctDNA changed from negative to positive relapsed within one month after transformation.
Conclusion
Postoperative ctDNA could be a promising biomarker to indicate the recurrence risk for NSCLC patients after radical surgery.
