CAVEOLIN-1 expression in brain metastasis from lung cancer predicts worse outcome and radioresistance, irrespective of tumor histotype

Abstract

Brain metastases develop in one-third of patients with non-small-cell lung cancer and are associated with a dismal prognosis, irrespective of surgery or chemo-radiotherapy. Pathological markers for predicting outcomes after surgical resection and radiotherapy responsiveness are still lacking. Caveolin 1 has been associated with chemo- and radioresistance in various tumors, including non-small-cell lung cancer. Here, caveolin 1 expression was assessed in a series of 69 brain metastases from non-small-cell lung cancer and matched primary tumors to determine its role in predicting survival and radiotherapy responsiveness. Only caveolin 1 expression in brain metastasis was associated with poor prognosis and an increased risk of death (log rank test, p = 0.015). Moreover, in the younger patients (median age of <54 years), caveolin 1 expression neutralized the favorable effect of young age on survival compared with the older patients. Among the radiotherapy-treated patients, an increased risk of death was detected in the group with caveolin 1-positive brain metastasis (14 out of 22 patients, HR=6.839, 95% CI 1.849 to 25.301, Wald test p = 0.004). Overall, caveolin 1 expression in brain metastasis from non-small-cell lung cancer is independently predictive of worse outcome and radioresistance and could become an additional tool for personalized therapy in the critical subset of brain-metastatic non-small-cell lung cancer patients.

Multifaceted Roles of Caveolin-1 in Lung Cancer: A New Investigation Focused on Tumor Occurrence, Development and Therapy

“…Nevertheless, in some cases, Cav-1 can also act as a positive predictor. Duregon et al identified that lung AC patients with proline-to-leucine mutations at codon 132 (P132L) of Cav-1 had a longer survival time than patients without such mutations [120]. A study may partly account for this situation.…”

Caveolin‐1, cancer and therapy resistance

“…In line with this idea, low CAV1 expression in pre-treatment biopsies from patients with locally advanced colorectal cancer has already been correlated with better rates of local control and overall survival. 107,108 Hossain et al then identified the mechanism that underlies the tyrosine kinase receptor TIE2 which regulates DNA repair machinery in human gliomas, as DNA repair pathways enable malignant gliomas to survive genotoxic-induced DNA damage, and thus foster radioresistance. 109,110 Herein, TIE2-mediated CAV1 phosphorylation and the formation of CAV1-TIE2 complexes was followed by caveolae-mediated endocytosis and nuclear translocation, finally resulting in enhanced DNA repair mechanism and radioresistance.…”

Common Prognostic Scoring Systems for Patients Presenting with Brain Metastases

“…The MRI characteristics were further studied in 65 patients with single BM for their predictive power on survival outcomes, and the preoperative diffusion-weighted imaging signal intensities were found to be significantly correlated with survival results [48]. In another study of 69 BM patients from non-small-cell lung cancer caveolin-1 was surveyed for its predictive role on survival and radiotherapy responsiveness as a pathologic marker [49]. The study outcomes convincingly demonstrated that caveolin-1 expressing BMs were linked with notable more dismal prognoses and an increased risk of death (p=0.015).…”