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Hauke Winter



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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): Hauke Winter

      • Abstract
      • Slides

      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): Hauke Winter

      • Abstract
      • Slides

      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.

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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-04 - The Prognostic Value of Serological Tumor Markers in Lung Cancer – Analysis of 13,373 Cases (ID 800)

      10:15 - 18:15  |  Author(s): Hauke Winter

      • Abstract
      • Slides

      Background

      Serological tumor markers such as Carcinoembryonic Antigen (CEA), Cytokeratin 19 Fragments (Cyfra 21-1) and Neuron Specific Enolase (NSE) have been shown to provide prognostic information in lung cancer. We have introduced an algorithm to combine two markers (CEA, Cyfra 21-1) into a new variable the so called tumor marker index (TMI). TMI is defined as the geometric mean of normalized marker values (Muley et al, Anticancer Res 24:1953-56, 2004).

      Method

      We have uploaded available routine tumor marker data from various sources (excel sheets, extracts from laboratory IT-systems and from our clinical cancer registry) into the clinical research data warehouse based on i2b2/tranSMART using Talend Open Studio procedures. We extracted selected clinical parameters together with tumor marker data for further analyses with the statistical software package SPSS 25.0 (IBM Deutschland GmbH, Ehningen). Pretherapeutical tumor markers were measured with Roche Elecsys (Roche Diagnostics GmbH, Penzberg). A complete set of tumor marker data for the calculation of TMI1 (CEA, CYFRA21-1) and TMI2 (CEA, CYFRA21-1, NSE) was available in n=13373 and n=13174 cases, respectively.

      Result

      The median value (range) for TMI1 and TMI2 was found to be 0.94 (0.01-1311.98) and 1.01 (0.01-201.67), respectively. Besides the validation of our originally published prognostic cut off value of 0.54 for TMI1 (Muley et al, Lung Cancer 2008, 60:408-415) in 1315 p-stage I NSCLC patients (figure), we found additional cut off values for the differentiation of prognostic groups in the data set of all patients. Up to 7 groups with patient number >1800 could be significantly differentiated by both indices (table).

      muley_fig_wclc2019.png

      TMI1
      cutoff

      Patients
      (n)

      Median
      (mos)

      HR

      TMI2
      cutoff

      Patients
      (n)

      Median
      (mos)
      HR
      0.42 2,014 62.4 1 0.55 1,989 82.1 1
      0.58 1,837 35.3 1.33 0.70 1,774 40.8 1.39
      0.79 1,891 26.3 1.61 0.89 1,913 23.5 1.92
      1.11 1,913 17.2 2.12 1.15 1,868 16.5 2.49
      1.76 1,916 13.3 2.70 1.64 1,871 13.7 3.09
      3.54 1,891 10.2 3.44 2.73 1,883 9.4 4.34
      >3.54 1,910 6.7 5.00 >2.73 1,871 6.6 5.97

      Conclusion

      The usefulness of our clinical data warehouse for assembling and structuring of clinical parameters and tumor marker data is warranted. The value of TMIs for the stratification of individual risk groups could be verified in one of the world wide largest series of tumor marker data in lung cancer.

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