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Petros Christopoulos
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EP1.03 - Biology (ID 193)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.03-30 - FAM83A and FAM83B as Prognostic Biomarkers and Potential New Therapeutic Targets in NSCLC (Now Available) (ID 587)
08:00 - 18:00 | Author(s): Petros Christopoulos
- Abstract
Background
Although targeted therapy improved survival rates in the last decade, non-small cell lung cancer (NSCLC) is still the most common cause of cancer related death. As most precision medicines lead to resistance, the challenge of identifying new targets for further effective therapies still remains. The FAMily with sequence similarity 83 (FAM83) members have recently been described as novel oncogenes in numerous human cancer specimens and shown to be involved in EGFR signaling. However, their function in cancer cells is largely unknown and especially their role in lung cancer remains unclear.
Method
Here, we investigated the expression and function of FAM83A and B in NSCLC. First, gene expression of the two FAM83 members was analyzed in a set of 362 NSCLC patients using qPCR. We further investigated relations in expression and their prognostic value using correlation and multivariate COX regression analyses. Functional assays in NSCLC cell lines were performed to analyze their involvement in proliferation, anchorage-independent growth, migration and the epidermal growth factor receptor (EGFR) pathway.
Result
We observed a highly increased gene expression level of FAM83A (ø = 68-fold) and FAM83B (ø = 20-fold) which resulted in poor survival prognosis (p < 0.0001 and p = 0.002). Correlation analysis showed poor relation between FAM83A and B in the two sub-histologies adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) but confirmed correlation between FAM83A and B and EGFR expression levels in patients and cell lines. Their expression was further influenced by EGFR pathway signaling and mutation status. Both genes affected cell proliferation and FAM83A depletion resulted in reduced migration and AIG.
Conclusion
The results support the hypothesis that FAM83A and B have different specific functions in the histological subtypes of NSCLC and might be new therapeutic targets.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-58 - Comprehensive Serial Biomaterial Acquisition in Advanced NSCLC: Feasibility, Challenges and Perspectives (ID 473)
09:45 - 18:00 | Author(s): Petros Christopoulos
- Abstract
Background
Availability of tumour material at baseline and disease progression is increasingly important for patient management in non-small-cell lung cancer (NSCLC), especially in tyrosine kinase and immune checkpoint inhibitor treatment. Here, we report the experience with prospective biobanking for advanced NSCLC from a pilot project in the academic setting.
Method
Main objective was the longitudinal collection of snap-frozen in addition to formalin-fixed paraffin-embedded (FFPE) biopsies required for routine diagnostics, along with blood samples and detailed clinical annotation using standardized questionnaires.
Result
Over five years, 205 patients were enrolled yielding 387 cryoconserved biopsies and 1098 serum, plasma and buffy-coat samples. The feasibility of obtaining cryoconserved in addition to FFPE biopsies was 89 % for newly diagnosed cases, but dropped down to 56 % and 47 % at first and second disease progression, respectively. Main obstacle was increased procedural risk due to patient deterioration, but no complications occurred. Biopsies had a tumour cellularity of 34 % and yielded 13.6 µg DNA and 12 µg RNA in median.
Conclusion
Despite the poor condition and limited prognosis of most NSCLC patients, systematic, serial biomaterial acquisition including routine collection of cryoconserved biopsies is feasible in order to facilitate individualized management and support research that will advance therapeutic options.
