49P - Numb serves as a prognostic biomarker and promotes lung adenocarcinoma brain metastasis

Background

Numb is a protein involved in asymmetric cell division determining cell fate across various research fields such as developmental neurobiology and cancer biology; however, its role remains poorly understood regarding brain metastases formation specifically within lung adenocarcinoma (LUAD).

Methods

In our previous study, five potential biomarkers for brain metastasis (BM) were identified using proteomic comparison of brain metastatic H1975-BrM cells and parent H1975 cells. We utilized the Cancer Genome Atlas Program (TCGA) database to analyze five genes expression at the level of mRNA in LUAD. Univariate and multivariate analyses were used to select independent risk factors that affect the prognosis of LUAD, and a nomogram model was established. The relationship between NUMB expression and LUAD immune infiltration was analyzed using TIMER, GEPIA database and TCGA data sets. In addition, clinical validation was performed using immunohistochemical (IHC) staining of lung tumor tissue from patients (n = 50) and investigated the relationship between NUMB and clinicopathology and prognosis in LUAD. The q-PCR and Western-blot assays were used to validate the expression of NUMB in vitro.

Results

After analyzing the prognostic value of those 5 differentially expressed genes, NUMB was the only gene associated with multiple prognostic indicators in LUAD patients using TCGA public database. Analysis of GEPIA datasets revealed that high NUMB expression in LUAD tissues correlates with poor patient survival. Multivariate analysis showed that Pathologic T stage, N stage, and high level of NUMB protein were independent prognostic factors of overall survival in patients with LUAD. These factors were used to construct the nomogram model. The analysis of TIMER, GEPIA database and TCGA data sets showed that the expression level of NUMB was negatively correlated with B cells, NK cells and Cytotoxic cells. Furthermore, NUMB was highly expressed in brain metastatic H1975-BrM cell line.

Conclusions

Our findings demonstrate that NUMB serves as an independent potential prognostic biomarker implicated not only in immune infiltration of LUAD, but also closely correlates with BM development.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University.

Funding

National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.