Clinical implication of Tiam1 overexpression in the prognosis of patients with serous ovarian carcinoma

Abstract

Abstract. T lymphoma invasion and metastasis 1 (Tiam1), a guanine nucleotide exchange factor, was originally identified as an invasion-and metastasis-inducing gene in T lymphoma cells. High expression levels of the human Tiam1 gene have been found in numerous human malignancies, suggesting a potential role as a modifier of tumor initiation and progression. However, little is known about the status of Tiam1 in ovarian carcinoma. The present study aimed to investigate the clinicopathological significance of high Tiam1 expression in serous ovarian carcinoma. Immunohistochemical staining for Tiam1 was performed in 182 patients with serous ovarian carcinoma, in 76 patients with ovarian borderline tumors and in 72 patients with benign ovarian tumors. Immunofluorescence staining was also performed to detect the subcellular localization of Tiam1 protein in SK-OV-3 ovarian carcinoma cells. The correlations between high Tiam1 expression and the clinicopathological features of the ovarian carcinomas were evaluated by the χ 2 test and Fisher's exact test. The overall survival (OS) rates were calculated by the Kaplan-Meier method, and the association between prognostic factors and patient survival was analyzed by the Cox proportional hazard model. Tiam1 protein showed a cytoplasmic and nuclear staining pattern in ovarian carcinoma. Strongly-positive Tiam1 protein expression was observed in 59.3% (108/182) of ovarian carcinomas, which was significantly higher than in benign serous tumors (12.5%; 9/72). Moreover, the rate of strongly-positive Tiam1 expression in borderline serous tumors (31.6%; 24/76) was also significantly higher than that in benign serous tumors. High Tiam1 protein expression was closely associated with a high histological grade, metastasis, advanced clinical stage and lower OS rates in ovarian carcinoma. Multivariate analysis indicated that Tiam1 was an independent prognostic factor, along with metastasis and clinical stage, in patients with ovarian carcinoma. In conclusion, Tiam1 expression is strongly associated with grade and outcome in ovarian carcinoma, and may serve as a useful molecular marker for clinical management.

<p>High Tiam1 expression predicts positive lymphatic metastasis and worse survival in patients with malignant solid tumors: a systematic review and meta-analysis</p>

“…Finally, a total of 17 studies were included in our meta-analysis. 6,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Basic characteristics of included studies A total of 17 studies enrolling 2,228 patients with malignant solid tumors were included in this metaanalysis. The included studies were published from 2006 to 2018.…”

“…11,14,16,19,21,22 Besides, 15 studies reported the association between Tiam1 expression and lymph node metastasis. 6,[8][9][10][12][13][14][15][17][18][19][20][21][22][23] All the included studies detected the Tiam1 expression in protein level. More details about the main characteristics of the included studies were presented in Tables 1 and 2.…”

“…T-cell lymphoma invasion and metastasis-inducing factor 1 (Tiam1), a specific guanine nucleotide exchange factor, a member of the Rho GTPase family, was first discovered by Habets et al and identified as an invasion and metastasisrelated gene in mice with aggressive T-cell lymphoma. 4,5 The TIAM1 gene is located in the q22 band of chromosome 21 and the centromeric end of the AML 21 gene and contains 2 exons (~7.3 kb) separated by 1 intron (14 kb) 6 Tiam1 is mainly expressed in normal brain and testis tissues with only minimal or no expressions detected in other normal tissues 7 Additionally, Tiam1 is highly expressed in various cancers as well, 6,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] and its overexpression in cancer cells could contribute to proliferation, [24][25][26][27] invasion and metastasis, [28][29][30][31] angiogenesis 32 and chemo-resistance of cancer cells 33 Of note, Tiam1 expressed in tumor stromal microenvironment also plays a role in regulating tumor invasion, metastasis and chemo-resistance. Cancer-associated fibroblast (CAF) is a major stromal cell in cancer stromal microenvironment.…”

Elevated expression of Tiam1 is associated with poor prognosis and promotes tumor progression in pancreatic cancer

“…A number of roles in the regulation of cellular functions are exhibited by Tiam1, and these roles depend on the substratum, the specific cell type, and other factors. 15 Li et al and Ding et al confirmed that the overexpression of Tiam1 predicts poor prognosis in ovarian carcinoma and hepatocellular carcinomas, 16 , 17 and Yang et al indicated that upregulation of Tiam1 correlates with poor prognosis in head and neck squamous cell carcinoma. 18 In line with these results, in this study, we assessed the expression level of Tiam1 in PDAC and found for the first time that Tiam1 was upregulated significantly in PDAC compared with that in non-cancerous tissues.…”

microRNA-1271-5p/TIAM1 suppresses the progression of ovarian cancer through inactivating Notch signaling pathway

“…Extensive evidences have illustrated that TIAM1, as a guanine nucleotide exchange factor, is involved in the invasion and metastasis of various human tumors, such as gastric cancer [ 15 ], prostate cancer [ 16 ] and breast cancer [ 17 ]. A previous report uncovered that TIAM1 expression is closely related with the grade and prognosis in OC and might be helpful for the management of clinic [ 18 ]. TIAM1 has also been indicated to facilitate the growth and invasion of OC cells through negatively being regulated by miR-22, miR-183 and miR-31 [ 19 ].…”