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Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
Prognostic significance of dynamin-related protein 1 expression in advanced lung adenocarcinoma
Yen-Lin Huang1, Yi-Jung Chen2, Yi-Hsiu Juan3
1Department of Pathology, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Background:
Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission and is activated by phosphorylation at serine 616. We previously demonstrated that DRP1 activation is regulated by epidermal growth factor receptor (EGFR) signaling and multiple kinases in lung adenocarcinoma, and is significantly associated with an increased risk of postoperative recurrence in early stage lung adenocarcinoma. However, it is unclear whether DRP1 activation is associated with worse prognosis in patients with advanced lung adenocarcinoma. This study is aimed to examine whether P(S616)-DRP1 expression is significantly related to the survival of patients with advanced lung adenocarcinoma.
Materials And Methods:
Biopsy samples were obtained from patients with stage IV lung adenocarcinoma. The activation status of DRP1 in cancer cells was quantified based on the immunohistochemical stain of phosphorylated DRP1 at serine 616 [P(S616)-DRP1]. Results of EGFR, ALK, ROS1, and KRAS mutations were retrieved from the medical records. The staining intensity and the histological scores (H-scores) of P(S616)-DRP1 were analyzed for association with progression-free survival (PFS) under first-line tyrosine-kinase inhibitors (TKIs) and with overall survival (OS).
Results:
Overall, 123 patients with stage IV lung adenocarcinoma constituted the study population, and 90 (73.2%) patients received TKIs as the first-line treatments. The median P(S616)-DRP1H-score was used to dichotomize the study population into the high (n = 61) and low (n = 62) DRP1 activation groups. DRP1 was significantly less phosphorylated in lung adenocarcinoma with EGFR, ALK, ROS1, and KRAS mutations. Importantly, in patients who received first-line TKIs, DRP1 phosphorylation was not significantly correlated with PFS and OS. Multivariate Cox proportional hazard models showed that high DRP1 activation in cancer cells was not significantly associated with worse OS in the study population (adjusted hazard ratio: 1.402, 95% confidence interval: 0.865-2.271, p = 0.170). Similar results were obtained in the analysis based on the intensities of P(S616)-DRP1 in cancer cells.
Conclusions:
Our data demonstrate that DRP1 phosphorylation is not related to the prognosis of patients with advanced lung adenocarcinoma.
