Thrombospondin-4 expression as a prognostic marker in hepatocellular carcinoma

Wu, Hong-Fen; Zhang, Guangcong; Li, Zhi; Ma, Jiamei; Huang, Xiangyang; Xiang, Tian; Jiang, Xuemei

doi:10.1016/j.gene.2019.02.049

Cited by 14 publications

(11 citation statements)

References 31 publications

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“…Like TSP-5, TSP-4 is reported to be associated with malignant potential, tumor growth, and progression in several cancers including gastric cancer, hepatocellular carcinoma, and gallbladder cancer (34)(35)(36)(37). However, our results showed no significant pathological role of TSP-4 expression in BC tissues.…”

Section: Discussioncontrasting

confidence: 68%

“…In short, although over 40% of patients were judged as positive for TSP-4 expression despite its lack of expression in normal urothelial cells, no significant role of TSP-4 was determined. Based on previous reports in other malignancies (34)(35)(36)(37), we speculate that TSP-4 might play significant roles in BC, except in cell survival and angiogenesis. In addition, TSP-4 expressed in stromal cells might play important roles in malignant aggressiveness, though the methods used in this study cannot detect such expression.…”

Section: Discussionsupporting

confidence: 54%

“…Overall, these studies suggest that TSP-4 expression in cancer cells plays a significant role in tumor growth and cancer cell progression. However, there are contrasting opinions regarding whether TSP-4 acts as a tumor-promoter or suppressor, based on different types of malignancies (34)(35)(36)(37)(39)(40)(41). Finally, we emphasize that further detailed studies using cancer cell lines, animal models, and clinicopathological data are necessary to discuss and conclude the clinical significance and pathological roles of TSP-4 in patients with BC.…”

Section: Discussionmentioning

confidence: 93%

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Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer

Harada

Miyata

Araki

et al. 2021

In Vivo

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Background/Aim: The pathological significance of thrombospondin (TSP)-1 and -2 in bladder cancer (BC) is well-known whereas that of 4 and 5 remains unclear. Our aim is to clarify the pathological significance and prognostic roles of TSP-3 to 5 expression in BC patients. Patients and Methods: TSP-3 to 5 expression, proliferation index (PI), apoptotic index (AI) and microvessel density (MVD) were evaluated in 206 BC patients by immunohistochemical techniques. Results: TSP-5 expression was positively associated with grade, T stage, metastasis, and worse prognosis. PI in TSP-5-positive tissues was significantly higher compared to negative tissues. In contrast, AI in TSP-5-positive tissues was significantly lower compared to negative tissues. Expressions of TSP-3 and 4 were not associated with any clinicopathological features, survival, PI, or AI. Conclusion: TSP-5 plays important roles in malignant behavior via cell survival regulation whereas the pathological significance of TSP-3 and TSP-4 in BC might be minimal.

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Section: Discussioncontrasting

confidence: 68%

Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 93%

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Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer

Harada

Miyata

Araki

et al. 2021

In Vivo

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“…Although it has been reported that THBS4 is highly expressed in cancer stroma, the significance of THBS4 in tumor stroma in the development of gastric cancer has been controversial. THBS4 was reported to stimulate the development of cancer [8, 10–13], whereas other studies found that THBS4 acts as a tumor suppressor [14, 15]. Few investigations have examined the clinicopathological significance of THBS4, and we conducted the present study to evaluate the clinicopathological significance of THBS4 expression in gastric cancer, especially in tumor stroma.…”

Section: Introductionmentioning

confidence: 98%

The clinicopathological significance of Thrombospondin-4 expression in the tumor microenvironment of gastric cancer

et al. 2019

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IntroductionThrombospondin-4 [1] is an extracellular glycoprotein involved in wound healing and tissue remodeling. Although THBS4 is reportedly frequently expressed in solid tumors, there are few reports of the clinicopathological features of carcinomas with THBS4 expression. We evaluated the clinicopathologic significance of THBS4 expression in gastric carcinoma (GC).Materials and methodsWe retrospectively analyzed the cases of 584 GC patients. The expression of THBS4 in each tumor was evaluated by immunohistochemistry. We then divided the patients into the THBS4-high (n = 223, 38.2%) group and THBS4-low (n = 361, 61.8%) group. THBS4 expression in cancer-associated fibroblasts (CAFs), normal-associated fibroblasts (NFs) and gastric cancer cell lines was examined by western blotting.ResultsTHBS4 is expressed on stromal cells with αSMA or Podoplanin expression in the GC microenvironment, but not expressed on cancer cells with cytokeratin expression. The western blot analysis results showed that CAFs (but not NFs and cancer cells) expressed THBS4. Compared to the THBS4-low expression status, the THBS4-high expression status was correlated with higher αSMA expression, higher invasion depth, lymph-node metastasis, lymphatic invasion, peritoneal cytology, peritoneal metastasis, larger tumor size, microscopic diffuse type, and the macroscopic diffuse infiltrating type. The THBS4-high group's 5-year overall survival rate was significantly poorer than that of the THBS4-low group. A multivariate analysis revealed that THBS4 expression was an independent prognostic factor.ConclusionTHBS4 is expressed on CAFs in the gastric cancer microenvironment. THBS4 from CAFs is associated with the metastasis of cancer cells, and is a useful prognostic indicator for gastric cancer patients.

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“…However, for the low resectable rate at the time of diagnosis the five-year survival rate is only 12.1% in all liver tumors patients ( Zeng et al, 2018 ). Some factors can predict the outcomes and prognosis of HCC, however, existed conventional prognostic indicators are poor at predicting the prognosis of HCC ( Wu et al, 2019 ; Sapisochin & Bruix, 2017 ). Therefore, discovering new marker for predicting the prognosis of HCC after surgical resection is crucial to improve its management and long-term survival.…”

Section: Introductionmentioning

confidence: 99%

Galectin-3 not Galectin-9 as a candidate prognosis marker for hepatocellular carcinoma

Kong

Jin

Cao

et al. 2020

PeerJ

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Background Galectins (Gal) are a family of protein that bind to the β-galactoside of glycoproteins. It modulates a variety of biological functions, such as tumor growth, angiogenesis and tumor metastasis. A series of experimental and clinical evidences have been reported to support a correlation between galectin expressions and neoplastic transformation, progression and prognosis. The objective of this study was to estimate the expression of Gal-3 and Gal-9 in order to evaluate their relation to hepatocellular carcinoma (HCC) -related clinical features and their prognostic values. Methods We evaluated Gal-3 and Gal-9 expression in 247 HCC patients by a tissue microarray immunohistochemistry method, then analyzed the relationship between expression levels of Gal-3 and Gal-9 protein and tumor parameters or clinical outcomes. Results The Gal-3 expression was significantly higher in tumor tissues compared with adjacent non-tumor tissues (P < 0.001), while no significant differences of Gal-9 was detected (P = 0.222). A higher Gal-3 expression was significantly associated with lymph-vascular invasion (P = 0.049), poor histological differentiation (P = 0.016), and no cirrhosis (P = 0.040). In contrast, a lower Gal-9 expression was related to lymph-vascular invasion (P = 0.012) and poor histological differentiation (P = 0.002). Survival analysis showed that patients with higher Gal-3 expression had worse overall survival (P = 0.012) , however no correlation was found between Gal-9 expression and survival (P = 0.185). Multivariate analysis showed that multiple tumor (HR = 1.94, 95% CI [1.36–2.78]), tumor size ≥ 5 cm (HR = 1.51, 95% CI [1.07–2.12]), Lymph-vascular invasion (HR = 1.45, 95% CI [1.00–2.10]) and Gal-3 expression (HR = 1.57, 95% CI [1.06–2.33]) were independent influencing factors of prognosis in patients with hepatocellular carcinoma. Conclusion Gal-3 was expected to serve as a novel prognostic marker of hepatocellular carcinoma, while Gal-9 expression was only related to tumor progression.

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Thrombospondin-4 expression as a prognostic marker in hepatocellular carcinoma

Cited by 14 publications

References 31 publications

Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer

Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer

The clinicopathological significance of Thrombospondin-4 expression in the tumor microenvironment of gastric cancer

Galectin-3 not Galectin-9 as a candidate prognosis marker for hepatocellular carcinoma

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