Journal of Cancer Therapeutics & Research

Journal of Cancer Therapeutics & Research

ISSN 2049-7962
Original Research

Aberrant NHERF1 expression as a biomarker in lung carcinoma

Deborah Belchis1*, Nathan Cuka2, Neeraj Sharma3, Rajni Sharma2 and Christopher D. Gocke2

*Corresponding author: Deborah Belchis

1. Johns Hopkins Bayview Medical Center 4940 Eastern Avenue, Baltimore MD 21224, USA.

Author Affiliations

2. Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.

3. McKusick-NathansInstitute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA.


Background: Na/H exchange regulator factor 1 (NHERF1/EBP50) isan adaptor/signaling protein that when aberrantly expressed has been associated with tumor development and progression. In some tumors this occurs through its interaction with the PIK3-PTEN-AKT pathway.

Objective: This study explores NHERF1 biomarker expression in lung cancers and, further, NHERF1 and PTEN expression and the PIK3CA-PTEN-AKT pathway in squamous cell lung carcinoma (SQCC).

Design: Phase 1: The immunohistochemical expression of NHERF1 was examined in a lung cancer microarray and correlated with histologic type of tumor and stage. Phase 2: NHERF1 and PTEN expression in 21 SQCC was correlated. Mutations in the PIK3CA/PTEN/AKT pathway were analyzed by NGS.

Results and conclusions: Phase 1: NHERF1 expression and histologic subtype strongly correlated (p<0.001). Small cell carcinomas were negative. SQCCs exhibited moderate to strong expression. Strong aberrant expression in adenocarcinomas correlated with lymph node metastases (p=0.005). Phase 2: 20 SQCC cases expressed NHERF1. PTEN was negative in 7 cases, heterogeneous in 2, and positive in 13. There was no correlation between NHERF1 and PTEN expression, arguing against cooperativity of the proteins in this setting. AKT, PTEN, and PIK3CA did not have detectable mutations. PTEN loss was not associated with an underlying genetic mutation, suggesting a different mechanism for deregulation.

Keywords: Lung cancer, NHERF1, PIK3CA-PTEN-AKT pathway

ISSN 2049-7962
Volume 5
Abstract Download