Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

doi:10.1016/j.bbrc.2013.12.106

Biochemical and Biophysical Research Communications

Volume 443, Issue 4, 24 January 2014, Pages 1141-1147

https://doi.org/10.1016/j.bbrc.2013.12.106 Get rights and content

Highlights

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Most of the adenocarcinomas and bronchioloalveolar carcinomas were LIPH-positive.
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LIPH is necessary for the proliferation of lung cancer cells in vitro.
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A high level of LIPH in serum is correlated with better survival in early phase lung-cancer patients after surgery.

Abstract

Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma.

Introduction

Lung cancer is one of the most frequent causes of cancer-related death worldwide in both men and women [1]. By histology, lung cancer is classified into small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). NSCLC is further classified into several major subtypes, such as adenocarcinoma (AC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC). Among NSCLCs, AC is the most frequent subtype of lung cancer [2]. Many genetic alterations have been reported to be involved in the initiation and progression of lung cancer [3], [4], [5], [6]. Moreover, recent studies using DNA microarrays demonstrated that gene expression patterns were distinct for lung cancers of different histological types [7], [8]. However, molecular markers for various lung cancers have not yet been established.

In this study, we investigated novel biomarkers for lung cancer using a public microarray database. We identified lipase member H (LIPH) as one of the genes significantly upregulated in lung AC and bronchioloalveolar carcinoma (BAC). Moreover, we show that LIPH was associated with better survival in lung cancer patients.

Section snippets

Cell culture

Sixteen NSCLC cell lines including 9 AC cell lines (PC-3, PC-14, RERF-LC-KJ, RERF-LC-MS, ABC-1, RERF-LC-Ad1, RERF-LC-Ad2, VMRC-LCD, and LC-2/Ad) and 7 squamous cell carcinoma (SCC) cell lines (PC-1, LC-1 sq, RERF-LC-AI, RERF-LC-Sq1, EBC-1, HARA, and LK-2) were used in this study. PC-1 and PC-14 cells were purchased from Immuno-Biological Laboratories (Fujioka, Japan). The human small airway epithelial cells (SAECs) and normal human bronchial epithelial cells (NHBECs) were purchased from Takara

LIPH expression is upregulated in lung adenocarcinoma

To identify novel biomarker genes for lung cancer cells, we surveyed publicly available human lung cancer microarray data deposited in the NCBI GEO database. When gene expression in the lung AC and SCC was compared by bioinformatic analysis, 701 genes were identified as upregulated by more than 2-fold in AC compared to SCC (data not shown). Among these, we further selected genes encoding secretory proteins that could be detected in the sera of lung cancer patients. LIPH was identified as one of

Discussion

The LIPH gene is located within 3q.27 region of chromosome 3 long arm which is reported as one of the most frequent areas of gene amplification in NSCLC [6]. In SCC, some of the tumor driver genes such as those encoding p63, phosphatidylinositol 3-kinase C catalytic subunit isoform-α (PI3KCA), and sex-determining region Y-box 2 (Sox2) are located at 3q [10], [11], [12]. The frequency of 3q.27 amplification in SCC has been reported to be around 30% [13], [14]. In this study, we detected similar

Acknowledgments

Human lung cancer cell lines, LC-2/Ad, RERF-LC-KJ, RERF-LC-AI, EBC-1, LK-2, and Sq-1 cells were provided by the RIKEN BRC through the National Bio-Resource Project of the MEXT, Japan. ABC-1, HARA, PC-3, RERF-LC-Ad1, RERF-LC-Ad2, RERF-LC-MS, RERF-LC-Sq1, and VMRC-LCD cells were also provided from JCRB Cell Bank.

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Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

Highlights

Abstract

Introduction

Section snippets

Cell culture

LIPH expression is upregulated in lung adenocarcinoma

Discussion

Acknowledgments

J. Thorac. Oncol.

Lung Cancer

Cancer Genet. Cytogenet.

J. Biol. Chem.

Genomics

Biochim. Biophys. Acta