Abstract 583P
Background
Non-small cell lung cancer (NSCLC) is a highly malignant form of cancer, distinguished by prompt metastasis, restricted response to chemotherapy, and unfavorable prognosis. As a result, there is an imperative requirement to investigate novel therapeutic approaches for NSCLC. Rhomboid-like protein 2 (RHBDL2) is overexpressed in various tumor cells and is associated with poor prognosis. However, the relevance of RHBDL2 to NSCLC remains unclear. This study aims to investigate the potential role of RHBDL2 as a diagnostic and prognostic biomarker for NSCLC, as well as its biological functions and molecular mechanisms in NSCLC.
Methods
TCGA, GEO, CTPAC, and HPA datasets were used to compare differential expression and pathological stratification of RHBDL2. Its prognostic and diagnostic role was evaluated using Kaplan-Meier curves and univariate and multivariate Cox regression analysis. In molecular biology experiments, protein expression was measured by immunohistochemical analyses and Western blot analyses. Protein-protein interactions were detected by co-immunoprecipitation assay and GST-pulldown assay. Cell proliferation was assessed by CCK8 assay and colony formation assay. Cell migration was performed by Transwell assays and wound healing assays.
Results
We found that RHBDL2 was highly expressed in human NSCLC cells and tissues, and was significantly correlated with distant metastasis and poor survival of NSCLC patients. Gain- and loss-of-function assays showed that RHBDL2 could accelerate NSCLC metastasis in vitro and in vivo. CO-IP/MS results suggested that RHBDL2 interacted with FGFR. RHBDL2 could directly interact with FGFR and affect its phosphorylation, and promote NSCLC cell migration by activating the downstream RAS/MEK/ERK signaling pathway. In addition, we also found that RHBDL2 was involved in osimertinib resistance through FGFR/RAS pathway.
Conclusions
Our study results indicate that RHBDL2 promotes NSCLC cell migration and osimertinib resistance by interacting with FGFR and thereby activating the RAS/MEK/ERK signaling pathway. Moreover, it can serve as a novel diagnostic and prognostic biomarker for NSCLC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study was funded by National Natural Science Foundation of China (81702887), Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province (2020E10021), Zhejiang Provincial Natural Science Foundation(LY19H310004,LTY21H160001), Scientific and Technological Developing Scheme of Hangzhou City (20191203B49), Science Research Foundation of Zhejiang Health Bureau (2020RC026).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
451P - The real-world efficacy and safety of anamorelin hydrochloride for Japanese unresectable non-small cell lung cancer patients with cachexia
Presenter: Daisuke Arai
Session: Poster Display
Resources:
Abstract
452P - The relationship between BCG immunotherapy and oxidative stress parameters in patients with non-muscle invasive bladder cancer
Presenter: Mukul Singh
Session: Poster Display
Resources:
Abstract
453P - Palonosetron plus megestrol acetate verses palonosetron plus dexamethasone in preventing moderately emetogenic chemotherapy-induced nausea and vomiting: A randomized, multicenter, crossover, phase II trial
Presenter: Qiaoqi Li
Session: Poster Display
Resources:
Abstract
454P - A multicenter randomized open-label phase II study investigating optimal antiemetic therapy for patients with advanced/recurrent gastric cancer treated with trastuzumab deruxtecan (T-DXd): EN-hance study
Presenter: Akira Ooki
Session: Poster Display
Resources:
Abstract
455P - Assessing model-predicted neurokinin-1 (NK1) receptor occupancy (RO) of netupitant to support efficacy over an extended time period
Presenter: Matti Aapro
Session: Poster Display
Resources:
Abstract
456P - Oxycodone/naloxone in moderate-to-severe cancer pain: A phase III study in China
Presenter: Ping Lu
Session: Poster Display
Resources:
Abstract
457P - Anticoagulation for terminal cancer patients with cancer associated venous thromboembolism
Presenter: Sang Bo Oh
Session: Poster Display
Resources:
Abstract
458P - Association between TSPAN15 and SLC44A2 genetic polymorphisms and venous thromboembolism in cancer patients
Presenter: Alshimaa Al Hanafy
Session: Poster Display
Resources:
Abstract
459P - Association between national health screening program and undertreatment of dyslipidemia in cancer survivors: A cross-sectional study
Presenter: Sujeong Shin
Session: Poster Display
Resources:
Abstract
460P - Group to grow: A systematic review of group-based interventions for post-traumatic growth on cancer patients
Presenter: Dyta William
Session: Poster Display
Resources:
Abstract