Predictive Value of Let-7A for Cancer Cell Repopulation Between Chemotherapy and Long-Term Survival: A Prospective Study.

OBJECTIVE:Repopulation during radiation is a classic theory in radiobiology. The long intervals between cycles of chemotherapy provide better micro-circumstance than radiation for the repopulation of cancer cells.METHODS:Patients with inoperable stage III and stage IV lung cancer were enrolled prospectively. Peripheral blood and tumor tissues were obtained before treatment and each cycle of chemotherapy to detect the serum let-7a expression and Ki-67 index.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 the Ki-67 index and serum let-7a before treatment (r =-0.667, P<0.001). The serum let-7a expression levels were upregulated or downregulated significantly during chemotherapy. Patients with relatively low baseline let-7a expression levels had significantly worse overall survival (OS) and progression-free survival (PFS) than patients with relatively high baseline serum let-7a levels (P<0.001, P=0.005, respectively).CONCLUSION:This prospective study demonstrated that let-7a was correlated with tumor proliferation in lung cancer, with high prognostic value. Furthermore, it showed that repopulation, as correlated with let-7a, may exist during chemotherapy, which would give us a new perspective in overcoming the chemoresistance of lung cancer and would help in determining individual treatment strategies.