Clinical Significance of Tensin 4 Gene Expression in Patients with Gastric Cancer

Abstract

Gastric cancer is the fifth most common cancer in the world and the third leading cause of cancer-related death (1). The outcomes of gastric cancer have been improved by gastrectomy with D2 lymph-node dissection and advances in chemotherapy (2). The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that 1 year of adjuvant chemotherapy with S-1, an oral fluoropyrimidine, significantly improves outcomes in patients with stage II/III gastric cancer who undergo gastrectomy with D2 dissection (3). However, recurrence rates after curative resection and adjuvant chemotherapy remain high in gastric cancer. In the ACTS-GC study, the 5-year overall survival (OS) rate was 84.2% in those with stage II disease, 67.1% in those with stage IIIA disease, and 50.2% in those with stage IIIB disease, even after adjuvant chemotherapy with S-1 (4). Further improvements in outcomes are likely to require personalized therapy based on biomarker analysis.We have searched for biomarkers of gastric cancer using DNA microarray analysis in patients with stage II/III gastric cancer who underwent curative resection and received adjuvant chemotherapy with S-1. We found that expression of the human tensin 4 (TNS4) gene in gastric cancer tissue was 23.52-times higher than that in paired adjacent normal mucosa (unpublished data). We, thus, focused on the clinical significance of TNS4 gene expression in gastric cancer.TNS4 is a member of the tensin gene family (5) and is also known as COOH-terminus tensin-like molecule (CTEN) (6). This gene family comprises four members (TNS1, TNS2, TNS3, and TNS4) and their products are localized in the cytoplasmic tails of integrins at focal adhesions. Tensins play important roles in various biological processes, such as cell adhesion, migration, proliferation, differentiation, apoptosis, and invasion (6-9). TNS4 expression is up-regulated in many cancer types (10)(11)(12)(13)(14), suggesting that overexpression of TNS4 may play a critical role in tumorigenesis.In this study, we evaluated the clinical significance of the relative expression of TNS4 in patients with stage II/III gastric cancer who underwent curative resection followed by adjuvant chemotherapy with S-1.

Whole Transcriptome Analysis Identifies TNS4 as a Key Effector of Cetuximab and a Regulator of the Oncogenic Activity of KRAS Mutant Colorectal Cancer Cell Lines

“…Considering the distinct tumor microenvironment between human and mouse, we cannot exclude the possibility that the selected genes may not have a complete physiological relevance. To avoid this issue, we focused on TNS4, a member of the Tensin protein family member, involved in a key cellular process including cell adhesion, migration, and proliferation, for further functional studies to test our hypotheses because TNS4 was found to be upregulated in various types of cancer and its expression is significantly correlated with KRAS mutation status in CRC cell lines based on our analysis [30,32,34,37,38,39,40].…”

“…GAPDH was used as the internal standard for normalization. The primer sequences used are as follows; TNS4 primer set (forward: 5′-CACCATGAAGTTCGTGATG-3′; reverse: 5′-CGGTATGAAGAGCTGTCC-3′), GAPDH primer set (forward: 5′-GGTGTGAACCATGAGAAGTATGA-3′; reverse: 5′-GAGTCCTTCCACGATACCAAAG-3′) [30,31].…”

Tensins – emerging insights into their domain functions, biological roles and disease relevance

“…However, we did not observe the development of pancreatic cancer in our TNS3knockout mice (our unpublished data). High levels of CTEN are reported to be prognostic markers for patients with melanoma (Sjoestroem et al, 2013), breast cancer (Albasri et al, 2011b), gastric cancer (Aratani et al, 2017;Sakashita et al, 2008;Sawazaki et al, 2017), colorectal cancer (Albasri et al, 2011a), hepatocellular carcinoma (Chen et al, 2014) and lung adenocarcinoma (He et al, 2018;Misono et al, 2019).…”

Untitled

“…Upregulated in tumour tissues compared to adjacent normal mucosa. High TNS4 expression associated with poorer 5-year overall survival (Sawazaki et al, 2017).…”