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Panpan Zhang
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MA27 - Novel Drugs and PDX Models (ID 931)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 206 BD
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MA27.11 - Genomic Sequencing and Editing Revealed the GRM8 Signaling Pathway as Potential Therapeutic Targets of Squamous Cell Lung Cancer (ID 12246)
14:40 - 14:45 | Presenting Author(s): Panpan Zhang
- Abstract
Background
Lung cancer is the leading cause of cancer death worldwide. Squamous cell carcinoma (LUSC) is one subtype of non-small-cell lung cancer (NSCLC), and ranks at the second of lung cancer incidence. Although targeting receptor tyrosine kinases (RTKs) had already brought better clinical outcomes to NSCLC patients carrying corresponding mutations, very few mutated targets had been identified in LUSC subtype, probably because of the lack of mutation hotspot and functional validation of mutated candidate.
a9ded1e5ce5d75814730bb4caaf49419 Method
The whole exome (WES) and whole genome (WGS) sequencing and CRISPR-Cas9 genome editing techniques were integrated to explore and validate novel targeting candidates from 11 groups of LUSC primary tumors and corresponding patient-derived xenografts (PDXs).
4c3880bb027f159e801041b1021e88e8 Result
The WES data revealed high homologies on the mutation types and signatures among primary tumor and different passages of PDX tumor samples. Nine significant genes carrying single nucleotide variations (SNVs) and three carrying copy number variations (CNVs) were identified as targeting candidates from WES and WGS data based on the mutation frequency and driver gene analysis. The oncogenic or tumor suppressor functions of those 12 candidates were validated through CRISPR-Cas9 loss-of-function system in tumor cells derived from PDX tissues carrying corresponding mutations and in normal bronchial epithelial cell-line. Furthermore, using CRISPRa transcriptionally activating system, one novel candidate, Metabotropic glutamate receptor 8 (GRM8) was elucidated to promote the survival of LUSC tumor cell through inhibiting cAMP pathway and activating MAPK pathway.
8eea62084ca7e541d918e823422bd82e Conclusion
The components of GRM8 signaling pathway could serve as potential targets of squamous cell lung cancer.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-67 - The Prognostic Analysis of Lung Cancer Patients with Occult Malignant Pleural Disease at Thoracotomy (ID 13270)
16:45 - 18:00 | Author(s): Panpan Zhang
- Abstract
Background
This study aims to determine the clinicopathological prognostic factors for occult malignant pleural disease (MPD) first detected at thoracotomy in patients with non-small cell lung cancer (NSCLC) and assess the outcome of surgical intervention.
a9ded1e5ce5d75814730bb4caaf49419 Method
A total of 120 patients with MPD at thoracotomy from January 2006 to October 2016 were evaluated. Survival curves were estimated by the Kaplan–Meier method, and Cox regression analysis was performed to validate the selected risk factors. Clinical and pathologic parameters were balanced by propensity score matching when assessing surgical intervention.
4c3880bb027f159e801041b1021e88e8 Result
With a median follow-up of 34 months, the 5-year overall survival of 120 patients was 28.0%. Multivariate analyses showed male (p=0.044), advanced T stages (p<0.001), advanced N stages (p=0.02), pleural invasion in image (p=0.005), pleural effusion (p=0.027), surgical intervention (p=0.008) and EGFR status (p=0.003) were independent predictors of survival. The 5-year survival rate and median survival time (MST) for 21 patients with lobectomy were 71.6% and undefined, compared with 25.6% and 40.0 months in 46 patients with sublobectomy. When 53 patients only subjected to open-close surgery, their 5-year survival rate and MST were 23.4% and 30.2 months. After propensity score matching, both 21 patients were included in lobectomy group and sublobectomy /open-close group. The overall survival of lobectomy group was better than the control group (p=0.046).
8eea62084ca7e541d918e823422bd82e Conclusion
The prognosis of MPD patients first detected at thoracotomy was affected by gender, stage, pleural invasion, pleural effusion, surgical intervention and EGFR status. Lobectomy maybe confers better survival compared with sublobectomy and exploratory thoracotomy.
6f8b794f3246b0c1e1780bb4d4d5dc53
