Prognostic significance of aquaporins in human biliary tract carcinoma

Sekine, Satoshi; Shimada, Yutaka; Nagata, Takuya; Moriyama, Makoto; Omura, Tetsuya; Watanabe, Tomoko; Hori, Reiji; Yoshioka, Isaku; Okumura, Tomoyuki; Sawada, Shigeaki; Fukuoka, Junya; Tsukada, Kazuhiro

doi:10.3892/or.2012.1747

Cited by 20 publications

(21 citation statements)

References 36 publications

(40 reference statements)

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“…In order to avoid epithelial cell contamination during venipuncture, all samples were collected after discarding the first 2 ml blood. Red blood cells (RBCs) were mixed with 45 ml lysis buffer (155 mM NH 4 Cl, 10 mM KHCO 3 , 0.1 mM EDTA), followed by rotation for 8 min and centrifugation (600 x g for 5 min) to remove RBCs. Resulting cell pellet was resuspended in PBS and subsequently incubated with 0.5 ml of antileukocyte surface marker CD45 monoclonal antibody coated magnetic beads for 30 min, followed by separation of magnetic beads using a magnetic stand (Promega, Madison, WI, USA).…”

Section: Isolation Of Normal Colon Cells and Culture Of Colorectal Camentioning

confidence: 99%

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AQP5: A novel biomarker that predicts poor clinical outcome in colorectal cancer

Shan

Cui

et al. 2014

Oncology Reports

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Abstract. The aquaporins (AQPs) are water channel proteins that exhibit several properties related to tumor development. However, the expression and clinical significance of AQP5 in colorectal cancer, particularly the correlation with circulating tumor cells (CTCs), has not been elucidated. The aim of the present study was to determine whether or not the expression of AQP5 is a strong prognostic biomarker for colorectal cancer. The results showed that of 45 tumor specimens, 14 (31.1%) had high levels of expression of AQP5, 29 (64.4%) exhibited a moderate (intermediate) level of staining, and 2 (4.4%) had an absence of AQP5 staining. AQP5 was only occasionally detected in para-neoplastic [3/45 (6.67%)] and normal tissues [3/45 (6.67%)]. AQP5 protein overexpression frequently accompanied gene amplification detection with fluorescence in situ hybridization (FISH). Moreover, AQP5 expression in colorectal cancer cells was upregulated compared to normal colon cells. AQP5 overexpression was also associated with TNM stage (P=0.002), lymph node metastasis (P=0.016), and distant metastasis (P=0.000). The relationships between age, gender, histologic grade and tumor size with expression of AQP5 were not significant (P>0.05). A positive correlation between the number of CTCs and AQP5 expression (P<0.05) was demonstrated. In addition, patients who did not express AQP5 had a superior cumulative survival rate compared to patients with AQP5 positivity. AQP5 may be used as a novel biomarker for colorectal cancer aggressiveness and metastasis, but it does not reflect drug resistance.

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Section: Isolation Of Normal Colon Cells and Culture Of Colorectal Camentioning

confidence: 99%

“…Water molecules play a significant role in the progression of malignant epithelial tumors, an understanding of which is thus important in anticancer treatment strategy (4). Aquaporins (AQPs) are a family of membrane water channels that are required for the transport of water through many secretory and absorptive epithelia.…”

Section: Introductionmentioning

confidence: 99%

AQP5: A novel biomarker that predicts poor clinical outcome in colorectal cancer

Shan

Cui

et al. 2014

Oncology Reports

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“…These data indicate that KLF4 . On the basis of the total score (the sum of the intensity and distribution scores), each patient was classified into one of two groups: The low expression group (total score, 0-2) or the high expression group (total score, 3-5) (17,18).…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of KLF4 expression in gastric cancer

et al. 2016

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Abstract.To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients. IntroductionGastric cancer is a malignant tumor with a poor prognosis, and the various treatments available at present, including surgery, chemotherapy and radiotherapy, remain unsatisfactory (1). Development of gastric cancer is associated with a number of molecular abnormalities, the majority of which affect the downstream signal transduction pathways involved in cell growth and differentiation (2,3). Investigation into such molecules is expected to provide useful prognostic biomarkers of gastric cancer that will aid in determining the treatment plan for individual patients. For example, methylation of the XIAP-associated factor 1 promoter (4), and expression of 14-3-3σ (5) and miR-200c (6) have been reported to be important for the prediction of poor prognosis in gastric cancer patients; however, further investigation is required.Induced pluripotent stem (iPS) cells are cells that have acquired pluripotency following the introduction of various factors; octamer-binding transcription factor (Oct)3/4 and sex-determining region Y-box 2 (SOX2) plus Krüppel-like factor 4 (KLF4) and avian myelocytomatosis viral oncogene homolog (c-Myc), or Nanog and LIN28 have been shown to induce pluripotency in various murine and human cells (e.g., fibroblasts) (7,8). These pluripotency-inducing factors have been detected in embryonic stem cells, as well as in normal cells and cancer cells, including gastric cancer (9). Although these factors are necessary in order for stem cells to acquire pluripotency, it has been suggested that they may have oncogenic potential in normal cells (10).Expression of SOX2 has been reported to be important for tumorigenicity and chemoresistance (11). However, the inhibition of gastric cancer cell growth and the induction of apoptosis by SOX2 has also been rep...

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“…We previously reported that AQP-5 may be involved in the differentiation of human gastric carcinoma cells [6]. We also analyzed AQP-1, -4, -5, and -8 expression immunohistochemically using tissue microarray (TMA) in 81 biliary tract carcinoma samples [15]. Our results suggested that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma, although gallbladder and bile duct slightly differ in generation and organ function.…”

Section: Introductionmentioning

confidence: 99%

Role of Aquaporin-5 in Gallbladder Carcinoma

et al. 2013

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Background/Purpose: Aquaporins (AQPs) are important in controlling bile formation. However, the exact role in human gallbladder carcinogenesis has not yet been defined. Methods: AQP-5-expressing gallbladder carcinoma (GBC) cell lines (NOZ) were transfected with anti-AQP-5 small interfering RNA (siRNA). Growth, migration, invasion assay, and drug susceptibility tests were performed. Next, microRNA (miRNA) expression was analyzed by miRNA oligo chip (3D-Gene®). AQP-5 and AQP-5-related miRNA target gene expressions were also analyzed using tissue microarray (TMA) in 44 GBC samples. Results: Treatment with AQP-5 siRNA decreased cell proliferation, migration, and invasion. On the other hand, those cells increased IC₅₀ of gemcitabine. By performing miRNA assays, miR-29b, -200a, and -21 were shown to be highly overexpressed in cells treated with AQP-5 siRNA NOZ. When focusing on miR-21, phosphatase and tensin homolog (PTEN) was found to be a target of miR-21. In the TMA, AQP-5/PTEN coexpression was significantly associated with the depth of invasion and MIB-1 index (p = 0.003, 0.010). Survival of patients with a high AQP-5/PTEN coexpression was longer than that of patients with a low coexpression (p = 0.003). Conclusions: Our result suggested that miR-21 and PTEN may contribute to the role of AQP-5 in GBC. AQP-5 and PTEN cascades are favorable biomarkers of GBC.

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Prognostic significance of aquaporins in human biliary tract carcinoma

Cited by 20 publications

References 36 publications

AQP5: A novel biomarker that predicts poor clinical outcome in colorectal cancer

AQP5: A novel biomarker that predicts poor clinical outcome in colorectal cancer

Prognostic significance of KLF4 expression in gastric cancer

Role of Aquaporin-5 in Gallbladder Carcinoma

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