Overexpression of the Transmembrane Protein IQGAP3 Is Associated with Poor Survival of Patients with Gastric Cancer

Oue, Naohide; Yamamoto, Yuji; Oshima, Takashi; Asai, Ryuichi; Ishikawa, Akira; Uraoka, Naohiro; Sakamoto, Naoya; Sentani, Kazuhiro; Yasui, Wataru

doi:10.1159/000481890

Cited by 24 publications

(26 citation statements)

References 27 publications

(42 reference statements)

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“…As a member of B7 family, B7-H4 may provide negative signals to inhibit or reduce immune response [18]. So far no studies have been found demonstrating the relationship between IQGAP3 and CRC, our findings may verify the role of IQGAP3 played in tumorigenesis and tumor progression [40], and can further clarify the prognostic value of IQGAP3 in CRC patients.…”

Section: Discussionsupporting

confidence: 54%

Clinical value of detecting IQGAP3, B7-H4 and cyclooxygenase-2 in the diagnosis and prognostic evaluation of colorectal cancer

et al. 2019

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Background The IQ-motif-containing GTPase-activating protein (IQGAP) family comprises three members, IQGAP1, IQGAP2 and IQGAP3. IQGAP3 is the latest addition to the family. This study mainly investigated the novel marker IQGAP3 at serum and tumor tissue levels compared with the markers B7-H4 and cyclooxygenase-2 (COX-2) in patients with colorectal cancer (CRC) and in healthy individuals, aiming to evaluate the diagnostic and prognostic value of IQGAP3 for CRC. Materials and methods Serum samples were collected prior to any therapy in 118 CRC patients and as part of a routine examination in 85 healthy individuals. Serum IQGAP3, B7-H4 and COX-2 levels were measured using commercially available ELISA kits. Immunohistochemistry was performed to detect the IQGAP3, B7-H4 and COX-2 in tumor tissues and normal para-carcinoma tissues. The receiver operating characteristics (ROC) curve and the area under the curve (AUC) were used to evaluate and compare the diagnostic value of different serum tumor markers. Univariate and multivariate analyses were performed to identify the prognostic risk factors for CRC. Results IQGAP3, B7-H4 and COX-2 showed low or high expression in tumor tissues while no expression in normal para-carcinoma tissues. Serum levels of IQGAP3 in CRC group were significantly higher than those in healthy control group ( P < 0.001). The IQGAP3 AUC was 0.799, while the B7-H4 AUC was 0.795 and the COX-2 AUC was 0.796. IQGAP3 seemed to be superior to B7-H4 and COX-2 in detecting CRC, with the highest sensitivity among the three markers. Multivariate analysis showed that T stage, N stage, differentiation degree, TNM stage and both serum and tissue IQGAP3, B7-H4 and COX-2 levels were significant prognostic factors for CRC. Conclusions IQGAP3 has a better diagnostic efficacy than B7-H4 and COX-2 in detecting CRC and it has value in predicting the prognosis of patients with CRC. Electronic supplementary material The online version of this article (10.1186/s12935-019-0881-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 54%

Clinical value of detecting IQGAP3, B7-H4 and cyclooxygenase-2 in the diagnosis and prognostic evaluation of colorectal cancer

et al. 2019

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“…We previously analyzed the gene expression profile of spheroid colonies and parental cells derived from gastric cancer (GC) cell lines by microarray analysis [10]. We identified several genes upregulated in spheroid colonies, such as KIF11, KIFC1, and IQGAP3, that are required for spheroid colony formation in GC cell lines and are associated with poor survival of GC patients [10][11][12]. These genes are also required for spheroid colony formation in esophageal and colorectal cancer cells [13,14].…”

Section: Tdo2 Overexpression Is Associated With Cancer Stem Cells Andmentioning

confidence: 99%

TDO2 Overexpression Is Associated with Cancer Stem Cells and Poor Prognosis in Esophageal Squamous Cell Carcinoma

et al. 2018

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Objective: Esophageal cancer is one of the deadliest cancers in the world, and the main subtype is esophageal squamous cell carcinoma (ESCC), which comprises 90% of cases. Expression of tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan catabolism, has been linked with tumor survival and poor prognosis of brain and breast cancer. However, no studies have investigated the potential role of TDO2 in esophageal cancer. Here we explored the expression and biological significance of TDO2 in ESCC. Methods: TDO2 protein expression was evaluated in 90 ESCC tissue samples by immunohistochemistry. TDO2 function in ESCC cell lines and spheroid colony formation were evaluated by RNA interference (RNAi). Results: TDO2 overexpression was associated with tumor stage, recurrence status, and the CD44 cancer stem cell marker in ESCC. TDO2 overexpression was correlated with poor outcome of ESCC patients. Inhibition of TDO2 expression by RNAi in TE-10 and TE-11 cell lines reduced both the number and the size of spheroid colonies as well as cell proliferation. Knockdown of TDO2 expression also induced inactivation of the epidermal growth factor receptor signaling pathway. Conclusion: Our results imply that TDO2 could play an important role in the progression of ESCC. Furthermore, TDO2 may be a potential therapeutic target in ESCC.

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Section: Introductionmentioning

confidence: 99%

“…Overexpression of IQGAP3 has been observed in lung, liver, pancreatic and gastric cancer[8-11]. Recently, IQGAP3 expression was found to be related to clinical stage and was an independent prognostic classifier of gastric cancer patients: IQGAP3 knockdown reduced both the number and size of the spheres formed by the gastric cancer cell line MKN-74 and inhibited the phosphorylation of Akt and Erk1/2[11]. In hepatocellular carcinoma, IQGAP3 was reported to function as an important regulator of epithelial-mesenchymal transition (EMT) and metastasis by activating the transforming growth factor (TGF)-β signaling pathway[9].…”

Section: Introductionmentioning

confidence: 99%

IQGAP3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

Hua

Long

zhang

et al. 2018

Preprint

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Background: IQ motif-containing GTPase activating 24 protein 3 (IQGAP3), the latest found protein of IQGAP family, 25 may act as a crucial factor in the process of cancer development 26 and progression; however, its clinical value in breast cancer 27 remains unestablished so far. Our team explored the correlation 28 between IQGAP3 expression profile and the clinicopathological 29 features in breast cancer. Methods: IQGAP3 levels in breast 30 cancer cell lines and tumor tissues were detected by real-time 31 PCR and western blotting and compared to the normal control 32 groups. Protein expression of IQGAP3 was evaluated 33 immunohistochemically in specimens (archived paraffin 34 embedded) of 257 breast cancer patients. We also analyze the 35 association between IQGAP3 expression and the clinical 36 characters and prognosis. The relationship between IQGAP3 37 expression and sensitivity to radiation therapy was determined 38 by subgroup analysis. Results: There was significant 39 upregulation of IQGAP3 in breast cancer cell lines and human 40 tumor tissues at both the mRNA and protein level compared to 41 the normal ones. In addition, 110/257 (42.8%) of archived 42 paraffin embedded breast cancer specimens had high protein 43 expression of IQGAP3. High expression of IQGAP3 was 44 significantly related to clinical stage (P=0.001), T category 45 (P=0.002), N category (P=0.001), locoregional 46 recurrence(P=0.002), distant metastasis (P=0.001), and vital 47 status (P=0.001). Univariate and multivariate statistical analysis 48showed that IQGAP3 was an independent prognostic factor of 49 the whole cohort breast cancer patients (P=0.003, P=0.001). 50Subgroup analysis revealed IQGAP3 expression correlates with 51 radiation therapy resistance and was also an independent 52 predictor for radiation therapy outcome. Conclusions: Our 53 findings suggest that high IQGAP3 expression predicts poor 54 prognosis and radiation therapy resistance in breast cancer. In 55 addition, IQGAP3 may be a reliable novel biomarker to provide 56 personalized prognostication and identify patients who can 57 profit from more aggressive RT regimen for improving the 58 survival of breast cancer patients. 59 1. Introduction 62 Breast cancer is the most frequent malignancy in women and the 63 second leading cause of cancer-related deaths worldwide[1]. Radiation 64 therapy (RT) is an indispensable part of the systemic therapeutic regimen 65 of breast cancer. Despite great progress in RT over recent years, 66 locoregional recurrence and distant metastasis after RT remain key 67 problems decreasing the survival of breast cancer patients [2]. 68 Locoregional recurrence results from the presence or evolution of 69 radioresistant tumor cells for which standard fractionated RT doses are 70 sublethal[3]. Currently, there is a dearth of clinically available 71 predictive biomarkers to indicate the optimal radiation dosing in breast 72 cancer, which leads to suboptimal treatment of these patients[4]. 73 Therefore, further researches to identify novel biomarkers a...

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Overexpression of the Transmembrane Protein IQGAP3 Is Associated with Poor Survival of Patients with Gastric Cancer

Cited by 24 publications

References 27 publications

Clinical value of detecting IQGAP3, B7-H4 and cyclooxygenase-2 in the diagnosis and prognostic evaluation of colorectal cancer

Clinical value of detecting IQGAP3, B7-H4 and cyclooxygenase-2 in the diagnosis and prognostic evaluation of colorectal cancer

TDO2 Overexpression Is Associated with Cancer Stem Cells and Poor Prognosis in Esophageal Squamous Cell Carcinoma

IQGAP3 Overexpression Correlates with Poor Prognosis and Radiation Therapy Resistance in Breast Cancer

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