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Yan Zong



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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-62 - A New Method for Non-Invasive Prediction of Radiotherapy: SDH5 Depletion Enhances Radiosensitivity by Regulating P53 (ID 12871)

      12:00 - 13:30  |  Author(s): Yan Zong

      • Abstract

      Background

      Radiotherapy is an important and effective treatment for lung cancer. Some molecules can predict the effect of radiotherapy, but it is an invasive test that will cause trauma to patient. So the development of reliable non-invasive methods for predication of radiotherapy has become essential to guide therapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We initiated an analytical, observational, open, and retrospective study (ChiCTR1800014878) of 53 patients with stage III lung adenocarcinoma who were ready for radiotherapy. The performance status (PS) scores of the patients are all over 2. Blood and tumor tissue before treatment were collected to detect SDH5 concentration. We then evaluated the prognostic role of SDH5 expression in these patients. To further verify the effect of SDH5 on radiosensitivity, two mice models (orthotopic mice bearing lung cancer and SDH5 gene knock-out mice) were established and the internal mechanism between SDH5 and radiotherapy was explored.

      4c3880bb027f159e801041b1021e88e8 Result

      The patients whose tumor shrink significantly one month after radiotherapy had lower expression of SDH5 in tumor, and loss of SDH5 expression correlated with down regulation of DNA-PKcsThr2609 and ku86. More importantly, SDH5 can be directly detected in blood by qRT-PCR, and the result is consistent with that in tissue. And more exciting, patients with deficiency of SDH5 had longer PFS and OS after radiotherapy, and the results in blood and in tumor are consistent. To further verify the effect of SDH5 on radiosensitivity, in vivo experiments were carried out. In the orthotopic model, SDH5 knock down tumors showed higher radiation sensitivity with smaller volume. In SDH5 knock-out mice, lung epithelial cells exhibited elevated DNA damage after radiation. Moreover, our data indicated that SDH5 depletion causes P53 translocated from cytoplasm to nucleus, which enhances radiosensitivity of non-small cell lung cancer. Furthermore, consistent with in vivo data, the tumor growth was partially reversed when p53 was co-depleted with SDH5.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this experiment we found that SDH5 regulated radiosensitivity by P53 and it can be detected in tumor tissue. It is a suitable marker for predicting radiosensitivity. More than this, the expression of SDH5 can be directly measured by qRT-PCR in the blood, and it is consistent with that in the tumor tissue. This provides a novel non-invasive method for predicting the radiosensitivity of the patients unable to tolerant the biopsy.

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