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Chandra Goparaju

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    MA23 - Early Stage Lung Cancer: Present and Future (ID 926)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 10:30 - 12:00, Room 105
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      MA23.01 - Buffy Coat Immunooncologic Diagnosis and Prognosis of pStage I Lung Adenocarcinoma (ID 12453)

      10:30 - 10:35  |  Author(s): Chandra Goparaju

      • Abstract
      • Presentation
      • Slides


      Accurate diagnosis of CT detected pulmonary nodules is crucial to decrease futile minimally invasive resections. We hypothesize that the circulating cellular microenvironment (buffy coat [BC]) containing granulocytes, mononuclear cells, and platelets presents immunologic transcriptional profiles for distinguishing adenocarcinoma from granulomas, and can prognosticate pStage I adenocarcinomas.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      BC total RNA was extracted from 48 pStage I adenocarcinomas having R0 resection and 23 granuloma patients found at surgery. Of the cancers, 23 did not recur either systemically or locoregionally and were matched by age, gender, and pack-years to progressors. RNA was profiled using Nanostring PanImmune Oncology panel for 770 immune genes and cytokines. A machine learning algorithm based on Elastic Net using 1000 loops of cross validation was run to estimate AUC, and logistic regression models used for prognostic classification.

      4c3880bb027f159e801041b1021e88e8 Result

      wclc 18 final.pngThe figure depicts the results of the diagnostic profiling in the upper panel (A-C), and prognostication in lower panel (D-F). Unsupervised heat map separated adenocarcinomas (grey) from granulomas, and among the gene set analysis, differences in interleukins, microglial function, antigen processing, cytokines and macrophage functions were the most significant for cohort discrimination. A 33 gene set signature was able to separate granuloma from cancer with mean AUCs of 0.982. Expresion of BC immune related genes were remarkably different between the patients who recurred, and there were differences in profiles of locoregional recurrences compared to systemic recurrences (data not shown).Patients with elevated T-regs but decreased T-cells were characterized by distant progression, while decreased mast cells and increased CD-8 and total T-cells were associated with local recurrence. A three step prognostication index using 19 genes could stratify these patients by time to progression (E,F).

      8eea62084ca7e541d918e823422bd82e Conclusion

      These encouraging data offer the potential for immune transcriptional signatures to better select patients for diagnosis/management of early stage adenocarcinoma. Further validation studies are underway for possible presentation at WCLC18.


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