Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value

• We demonstrate that the plasma proteome of lung squamous cell carcinoma patients are changed during radiotherapy.
• We demonstrate that using a combination LRG1 and CRP proteins patient survival can be predicted.Research in ContextLung cancer is the most frequent cause of cancer-related death world-wide. The main curative treatment is surgery but due to diagnosis at a late stage or complicating factors this is not an option for the majority of patients, and so radiotherapy is common. Radiotherapy is known to cause severe toxicity which can be life threatening but there is no markers which can be used to guide treatment. Therefore we have studied the changes in blood during radiotherapy, identifying two proteins which predict survival. These proteins may allow radiotherapy of lung cancer patients to be guided early during treatment.

Lung cancer is the most frequent cause of cancer-related death world-wide. Radiotherapy alone or in conjunction with chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Currently there is no predictive marker with clinical utility to guide treatment decisions in NSCLC patients undergoing radiotherapy. Identification of such markers would allow treatment options to be considered for more effective therapy. To enable the identification of appropriate protein biomarkers, plasma samples were collected from patients with non-small cell lung cancer before and during radiotherapy for longitudinal comparison following a protocol that carries sufficient power for effective discovery proteomics. Plasma samples from patients pre- and during radiotherapy who had survived > 18 mo were compared to the same time points from patients who survived < 14 mo using an 8 channel isobaric tagging tandem mass spectrometry discovery proteomics platform. Over 650 proteins were detected and relatively quantified. Proteins which showed a change during radiotherapy were selected for validation using an orthogonal antibody-based approach. Two of these proteins were verified in a separate patient cohort: values of CRP and LRG1 combined gave a highly significant indication of extended survival post one week of radiotherapy treatment.