Protein Expression Linked to Poor Outcomes After Radiotherapy for Resected NSCLC


Upregulation of a specific protein may be an indicator of radiation resistance in patients with resected non-small cell lung cancer (NSCLC) who received radiotherapy, according to research published in Clinical Cancer Research (online December 14, 2017; doi:10.1158/1078-0432.CCR-17-1455).

Postoperative radiation is often used as a maintenance therapy after surgical resection and chemotherapy for locally advanced NSCLC. However, locoregional failure and distant metastasis still occur at a high rate in this population. Further research is needed to better understand the mechanisms of therapeutic resistance.

Yifan Wang, MD, University of Texas MD Anderson Cancer Center (Houston, TX), and colleagues conducted a study to analyze proteins in NSCLC cells and categorize pathways that may contribute to radiation resistance. Researchers utilized reverse-phase protein arrays (RPPA) to profile the baseline expression of 170 total and phosphorylated proteins in 70 NSCLC cell lines. The significant markers identified were further analyzed in tissue microarrays (TMA) of specimens from 127 patients who had undergone surgical resection before postoperative radiotherapy.

Cox regression analysis and log-rank tests were utilized to identify potential predictive factors.

Researchers reported that among the 170 proteins or phospho-proteins they analyzed, a subset of 12 proteins was determined to correlate with radiation response parameters. After examining the TMA analysis of the 12 proteins showing the greatest differences in expression in the RPPA analysis, researchers noted that RAD50 had the strongest correlation with distant relapse-free survival, locoregional relapse-free survival, and disease-free survival.


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In a further in vitro analysis, Dr Wang and colleagues found that knockdown of RAD50 resulted in sensitized NSCLC cells to radiation, and that upregulation of RAD50 resulted in increased radiation resistance.

In their concluding remarks, authors of the study wrote “Upregulated RAD50 may be a predictor of radioresistance in patients with lung cancer who received radiotherapy.” Further research is necessary to confirm the validity of this finding.—Zachary Bessette