Sequential Serum Let-7 Is a Novel Biomarker to Predict Accelerated Reproliferation During Fractional Radiotherapy in Lung Cancer

Clin Lung Cancer. 2016 Sep;17(5):e95-e101. doi: 10.1016/j.cllc.2016.03.010. Epub 2016 Mar 29.

Abstract

Background: Accelerated reproliferation, usually deemed to occur late during the course of radiation therapy, is an important factor resulting in radiotherapy failure. The identification of strategies that accurately reflect accelerated reproliferation might help to determine radiotherapy strategy, and thus implementation of individualized treatment.

Patients and methods: Patients with lung cancer were enrolled from Shandong Cancer Hospital and Institute in China between March 2014 and March 2015. Tumor tissue and sequential peripheral blood samples were obtained before treatment and during radiotherapy to detect Ki-67 and let-7 expression.

Results: We found a strong correlation between serum let-7 and tissue Ki-67 before treatment (r = -0.773; P = .003). Patients with a high level of baseline serum let-7 expression level had significantly better overall survival (the overall survival were 100% and 27.3%, respectively; P = .024). For patients with a relatively low expression level of baseline serum let-7, there was a peak of expression levels at week 4 (the mean expression levels were 1.40, 5.01, and 1.36, respectively). However, for patients with relatively high expression levels of baseline serum let-7, the expression levels were constantly downregulated at week 4 and 6 compared with the original (the mean expression levels were 6.16 vs. 1.34 vs. 0.80, respectively).

Conclusion: The study showed that serum let-7 expression level could reflect the proliferation of tumor tissue reliably in patients with lung cancer. Furthermore, the study might change conventional views of accelerated reproliferation. We showed that initial accelerated proliferation exists in patients with a relatively slow proliferation rate before radiotherapy, and late course accelerated reproliferation exists in patients with relatively fast proliferation before radiotherapy.

Keywords: Bronchogenic; Carcinoma; MicroRNA; Prognosis; Proliferation; Radiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Cell Proliferation / genetics
  • China
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Ki-67 Antigen / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Reproducibility of Results
  • Survival Rate
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • MicroRNAs
  • mirnlet7 microRNA, human