Reduced expression of the claudin-7 gene correlates with venous invasion and liver metastasis in colorectal cancer

Abstract

Abstract. Claudins, members of a large family of adherent junction proteins, regulate the integrity and function of tight junctions and influence tumorigenesis. Studies have suggested that altered levels of different claudins are related to carcinoma-cell invasion and disease progression. This study examined the relationship between the relative expression of claudin genes and clinicopathological factors, especially invasion and metastasis, in patients with colorectal cancer. We studied surgical specimens of cancer tissue and adjacent normal mucosa from 205 patients with untreated colorectal carcinoma. The relative expression levels of claudin-1, -3, -4 and -7 mRNA in cancer and in normal adjacent mucosa were measured by quantitative real-time, reverse-transcription polymerase chain reaction. The relative expression levels of the claudin-1, -3 and -4 genes were higher in cancer than in normal adjacent mucosa, whereas the relative expression of the claudin-7 gene was similar. An analysis of the relationship between the clinicopathological features and gene expression showed that reduced expression of claudin-7 correlated with venous invasion and liver metastasis. There was also a correlation between claudin-3 and -4 gene expression. Our results suggested that a reduced expression of the claudin-7 gene might lead to venous invasion and liver metastasis in colorectal cancer. Reduced expression of the claudin-7 gene may thus be a useful predictor of liver metastasis in patients with colorectal cancer.

Claudin-1 Acts through c-Abl-Protein Kinase Cδ (PKCδ) Signaling and Has a Causal Role in the Acquisition of Invasive Capacity in Human Liver Cells

“…Recent studies have provided evidence that claudins are aberrantly expressed in diverse types of human cancers, including hepatocellular carcinomas (HCCs) (9 -11), and are associated with the development and progression of cancer. In this context, it has been shown that decreased or abnormal expression of claudin-4 (CLD4) or claudin-7 (CLD7) is correlated with liver metastases (12)(13)(14). Moreover, downregulation of claudin-2 (CLD2) has been implicated in the development and progression of breast carcinomas (4).…”

Reduced expression of claudin-7 is associated with poor outcome in non-small cell lung cancer

“…A reduced claudin-7 expression correlates with a high tumor grade in prostatic adenocarcinoma (8). Oshima et al reported that a reduced claudin-7 expression correlates with venous invasion and liver metastasis in colorectal cancer (9). In contrast, an increased claudin-7 expression was reported in various cancer types, such as intestinal-type gastric adenocarcinomas (10), ovarian cancer (11) and cervical carcinoma (12).…”

Claudins and germ cell tumors

“…Claudin 16 expression, on the other hand, is associated with a better prognosis (26). Moreover, claudin 7 is downregulated in many cancers, such as breast and colon carcinoma, where its diminished expression is also associated with a poor prognosis (21,27).…”

“…In cancers derived from epithelial cells claudin expression may be increased or decreased (17).The expression of claudins varies in tumors at different sites (7) and is different in head and neck (18), pancreatic (19), colonic (20,21), ovarian (22), and breast cancers (23) as well as within the same site like in gastric cancer, where there is lower expression of claudins in diffuse carcinoma compared to the intestinal type (24). In breast cancer claudin 4 expression is increased and its expression is found in more aggressive types of tumors (25).…”