Sequential Serum Let-7a To Predict Accelerated Reproliferation Of Lung Cancer Cells During Chemotherapy And Long-Term Survival.

JOURNAL OF CLINICAL ONCOLOGY(2020)

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摘要
e21721 Background: Accelerated reproliferation during radiation is a classic theory in radiobiology. The long intervals between cycles of chemotherapy provides a better micro-circumstance to reproliferate of cancer cells. Few studies explored the accelerated reproliferation among cycles of chemotherapy. Methods: Patients with inoperable stage III and stage IV lung cancer from Shandong Cancer Hospital and Institute were enrolled prospectively. Tumor tissue and sequential peripheral blood were obtained before treatment and among cycles of chemotherapy to detect Ki-67 and let-7a expression. All patients were followed up to observe the occurrence and survival. Results: Fifty-two consecutive consenting patients were enrolled prospectively. The median follow-up was 13 months (range, 2–62 months). A strong correlation was found between serum let-7a and tissue Ki-67 before treatment (r = − 0.667, P < 0.001). The serum let-7a expression level was significantly upregulated at the time point after 2 and 4 cycles of chemotherapy, respectively, compared with the original. Then, at the time point after 6 cycles of chemotherapy, the expression levels of let-7a returned to relatively low level (F = 7.994, P < 0.001). Patients with high level of baseline serum let-7a had significantly better OS and PFS than patients with relatively low level of baseline serum let-7a (The 1-year OS and PFS rates were 80.6% VS 33.3%, X2 = 12.81, P < 0.001, and 54.2% VS 20%, X2 = 8.001, P = 0.005, respectively). Conclusions: The study showed that serum let-7a could reflect the proliferation of tumor tissue reliably in lung cancer, with high prognostic value. Furthermore, the study showed that accelerated reproliferation exists during treatment of cancer, not only in radiotherapy, but also in chemotherapy, which can give us a new perspective to overcome drug resistance of lung cancer, and would help in determining individual treatment strategy. This project was supported by National Natural Science Foundation of China (Grant No. 81502667) and Key Research and Development Plan of Shandong, China (Grant No. 2016GSF201167).
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