Significant elevation of CLDN16 and HAPLN3 gene expression in human breast cancer

Abstract

Abstract. Cancer development involves the destruction of tight junctions, deprivation of cell polarity, and increased cell mobility. Claudin 16 (CLDN16) is a tight junction protein and plays important roles in the maintenance of cell polarity, cellular arrangement, adhesion, paracellular transport, and ionic permeability of various epithelia. A novel link protein, HAPLN3, functions in hyaluronic acid binding and cell adhesion. Both genes are hypothesized to be related to cancer development and metastasis. The purpose of this study was to estimate the roles of the genes CLDN16 and HAPLN3 in breast cancer. A total of 146 samples were collected from breast cancer tissues and their adjacent normal breast tissues. Reverse transcription and real-time polymerase chain reaction were used to estimate gene expression levels. There were significantly increased gene expression of CLDN16 (p<0.0001) and HAPLN3 (p<0.0001) among breast cancer tissues compared with normal tissues, irrespective of clinical pathological parameters. The absolute increased gene expression level of CLDN16 was significantly negatively correlated with estrogen (r=-0.46; p<0.0001) and progesterone receptor (r=-0.384; p=0.001) staining density. However, a significantly positive correlation (r=0.24; p=0.04) between the absolute increased HAPLN3 gene level and human epidermal receptor 2 staining density was found. There was no significant association between overall survival and the two gene expression levels. The gene up-expression of both CLDN16 and HAPLN3 was suggested to be involved in the development of breast cancer and to be a biomarker and target treatment for breast cancer.

Genome-wide DNA methylome analysis identifies methylation signatures associated with survival and drug resistance of ovarian cancers

“…Our study identified 7 DMP-associated genes that could be a DNA methylation signature for determining high-grade and aggressive EOC. Of these 7 DMP-associated genes, hypomethylated CLDN16 is a member of the claudin family modulating cell polarity and is also a biomarker of breast cancer aggressiveness [ 55 ]. Additionally, hypermethylated LZTFL1 has been reported to be involved in maintaining cell differentiation [ 56 ], ABHD2 was found to control anoikis resistance in HGSOC [ 57 ], RNF144A was shown to be a tumor suppressor in governing breast cancer growth and metastasis [ 58 ], and HPS4 was shown to alter the functions of the small GTPases Rab32 and Rab38, which are associated with the recurrence of lung cancer [ 59 ], 60 .…”

Transcriptome Analysis Reveals MFGE8-HAPLN3 Fusion as a Novel Biomarker in Triple-Negative Breast Cancer

“…Besides, the expression of HAPLN3 was shown to be significantly higher in breast cancer tissues compared to the normal breast tissues. It was associated with the metabolism dysregulation, mobility, and migration of cancer cells in TNBC (42,43). These imply the value of MFGE8-HAPLN3 in guiding diagnosis and treatment choices in cancer.…”

Development of a Four-mRNA Expression-Based Prognostic Signature for Cutaneous Melanoma

“…HAPLN3 has been reported to play an important role in maintaining the stability of the extracellular matrix, thereby regulating the mobility and migration of tumor cells. Kuo et al (2010) found that HAPLN3 was significantly overexpressed in breast cancer tissues, but there was no correlation between HAPLN3 gene expression and overall survival. Ubiquinol cytochrome c reductase (UQCRFS1, also named as Rieske Fe-S protein) is a catalytic submit of complex III and plays an important role in the mitochondrial respiratory chain.…”