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Clinicopathological and prognostic values of fibronectin and integrin ?v?3 expression in primary osteosarcoma.

ABSTRACT: BACKGROUND:Osteosarcoma is a malignant bone tumor with a high potential for lung metastasis, and the prognosis for patients with metastatic disease is very poor. The interaction between fibronectin (FN) and integrin ?v?3 in soft-tissue sarcoma promotes cell migration, invasion, and lung metastasis. This study aimed to investigate the prognostic significance of FN and ?v?3 in osteosarcoma. METHODS:Immunohistochemistry and western blotting were used to detect the expression of FN and ?v?3 in 60 osteosarcoma specimens and in 30 osteochondroma specimens. Furthermore, correlations of FN and ?v?3 with the clinicopathological features of osteosarcoma patients were analyzed using the ?2 test and Fisher's exact test. Disease-free survival and overall survival of osteosarcoma patients were assessed using the Kaplan-Meier method and Cox proportional hazards model. The predictive accuracy of the model was determined by the Harrell concordance index. RESULTS:FN (P?

SUBMITTER: Shi K

PROVIDER: S-EPMC6350278 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Clinicopathological and prognostic values of fibronectin and integrin αvβ3 expression in primary osteosarcoma.

Shi Kai K Wang Sheng-Lin SL Shen Bin B Yu Feng-Qiang FQ Weng Dan-Feng DF Lin Jian-Hua JH

World journal of surgical oncology 20190128 1

<h4>Background</h4>Osteosarcoma is a malignant bone tumor with a high potential for lung metastasis, and the prognosis for patients with metastatic disease is very poor. The interaction between fibronectin (FN) and integrin αvβ3 in soft-tissue sarcoma promotes cell migration, invasion, and lung metastasis. This study aimed to investigate the prognostic significance of FN and αvβ3 in osteosarcoma.<h4>Methods</h4>Immunohistochemistry and western blotting were used to detect the expression of FN an ...[more]

PMID: 30691475

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Project description:The integrin α (ITGA) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in colon adenocarcinoma (COAD) remain elusive. The present study investigated the significance of the expression of ITGA genes in COAD from the perspective of diagnosis and prognosis. A COAD RNA‑sequencing dataset was obtained from The Cancer Genome Atlas. The present study investigated the biological function of the ITGA subfamily genes through bioinformatics analysis. Reverse transcription‑quantitative polymerase chain reaction was applied to investigate the distribution of integrin α8 (ITGA8) expression in COAD tumors and adjacent normal tissues. Bioinformatics analysis indicated that ITGA genes were noticeably enriched in cell adhesion and the integrin‑mediated signaling pathway, and co‑expressed with each other. It was also revealed through observation that the majority of gene expression was significantly low in tumor tissues (P<0.05), and diagnostic receiver operating characteristic curves revealed that most of the genes could serve as significant diagnostic markers in COAD (P<0.05), especially ITGA8 which had a high diagnostic value with an area under curve (AUC) of 0.989 [95% confidence interval (CI) 0.980‑0.997] in COAD (P<0.0001). In addition, ITGA8 expression was verified in clinical samples and it was revealed that it was higher in adjacent normal tissues (P=0.041) compared to COAD tissues, and the AUC was 0.704 (95% CI, 0.577‑0.831; P<0.0085). Multivariate survival analysis indicated that integrin α (ITGA5) may be an independent prognostic indicator for COAD overall survival. Gene set enrichment analysis indicated that ITGA5 may participate in multiple biological processes and pathways. The present study revealed that ITGA genes were associated with the diagnosis and prognosis of COAD. The mRNA expression of ITGA8 may be a potential diagnosis biomarker and ITGA5 may serve as an independent prognosis indicator for COAD.

Project description:BACKGROUND:Human epidermal growth factor receptor HER3 (ErbB3), especially in association with its relative HER2 (ErbB2), is known as a key oncogene in breast tumour biology. Nonetheless, the prognostic relevance of HER3 remains controversial. NEDD4-1 and NRDP1 are signalling molecules closely related to the degradation of HER3 via ubiquitination. NEDD4-1 and NRDP1 have been reported to contribute to HER3-mediated signalling by regulating its localization and cell membrane retention. We studied correlations between HER3, NEDD4-1, and NRDP1 protein expression and their association with tumour histopathological characteristics and clinical outcomes. METHODS:The prevalence of immunohistochemically detectable expression profiles of HER3 (n =?177), NEDD4-1 (n =?145), and NRDP1 (n =?145) proteins was studied in primary breast carcinomas on archival formalin-fixed paraffin-embedded (FFPE) samples. Clinicopathological correlations were determined statistically using Pearson's Chi-Square test. The Kaplan-Meier method, log-rank test (Mantel-Cox), and Cox regression analysis were utilized for survival analysis. RESULTS:HER3 protein was expressed in breast carcinomas without association with HER2 gene amplification status. Absence or low HER3 expression correlated with clinically aggressive features, such as triple-negative breast cancer (TNBC) phenotype, basal cell origin (cytokeratin 5/14 expression combined with ER negativity), large tumour size, and positive lymph node status. Low total HER3 expression was prognostic for shorter recurrence-free survival time in HER2-amplified breast cancer (p =?0.004, p =?0.020 in univariate and multivariate analyses, respectively). The majority (82.8%) of breast cancers demonstrated NEDD4-1 protein expression - while only a minor proportion (8.3%) of carcinomas expressed NRDP1. NEDD4-1 and NRDP1 expression were not associated with clinical outcomes in HER2-amplified breast cancer, irrespective of adjuvant trastuzumab therapy. CONCLUSIONS:Low HER3 expression is suggested to be a valuable prognostic biomarker to predict recurrence in HER2-amplified breast cancer. Neither NEDD4-1 nor NRDP1 demonstrated relevance in prognostics or in the subclassification of HER2-amplified breast carcinomas.

Project description:BackgroundVimentin is a member of the intermediate filament proteins and a canonical marker of the epithelial-mesenchymal transition (EMT), which is pivotal in tumorigenesis, metastasis and invasion in non-small cell lung cancer (NSCLC). The current meta-analysis aimed to investigate the associations between vimentin and prognosis and progression in NSCLC.MethodsDatabases with literature published in English, including PubMed, Web of Science, Embase, Science Direct, Wiley Online Library, Ovid, Cochrane Central Register of Controlled Trials, LILACS and Google Scholar, and the CNKI, VIP, CBM and WanFang databases in Chinese were used for the literature search. The key terms included (1) 'vimentin' OR 'vim' OR 'vmt' OR 'vm' OR 'hel113' OR 'ctrct30' and (2) 'pulmon*' OR 'lung' OR 'alveolar' and (3) 'cancer' OR 'carcinoma' OR 'tumor' OR 'adenocarcinoma' OR 'squamous' OR 'neoplas*' OR 'malignan*'. The data were combined by random effect model and the H value and I2 were used to assess the heterogeneity. All the meta-analysis was conducted using Stata 12.0.ResultsThirty-two qualified studies (4118 cases) were included in the current meta-analysis. Twelve studies with 1750 patients were included to assess the significance of vimentin in the overall survival (OS) of NSCLC; the pooled hazard ratio (HR) was 1.831 (confidence interval (CI): 1.315-2.550, P<0.001) in the univariate analysis and 1.266 (CI: 0.906-1.768, P = 0.167) in the multivariate analysis. Four studies with 988 cases were applicable to determine the significance of vimentin in the disease-free survival (DFS) of NSCLC; the pooled HR of the DFS was 1.224 (CI: 0.921-1.628, P = 0.164) in the univariate analysis and 1.254 (CI: 0.985-1.956, P = 0.067) in the multivariate analysis. Regarding the relationships between vimentin and clinicopathological factors, the pooled odds ratio (OR) with 3406 NSCLCs indicated that up-regulated vimentin was associated with smoking (OR = 1.359, CI: 1.098-1.683, P = 0.004), poor differentiation (OR = 2.133, CI: 1.664-2.735, P<0.001), an advanced TNM stage (OR = 3.275, CI: 1.987-5.397, P<0.001), vascular invasion (OR = 3.492, CI: 1.063-11.472, P = 0.039), lymph node metastasis (OR = 2.628, CI: 1.857-3.718, P<0.001), recurrence (OR = 1.631, CI: 1.052-2.528, P = 0.029) and pleural invasion (OR = 2.346, CI: 1.397-3.941, P = 0.001). There was no significant correlation between vimentin and age, gender, diameter, T stage, distant metastasis, or marginal invasion (P>0.05).ConclusionAn overexpression of vimentin may predict the progression and an unfavorable survival of NSCLC. Vimentin may represent a helpful biomarker and a potential target for the treatment strategies of NSCLC. Additional, prospective studies with large samples are necessary to confirm the significance of vimentin in NSCLC.

Dataset Information

Clinicopathological and prognostic values of fibronectin and integrin ?v?3 expression in primary osteosarcoma.

Publications

Clinicopathological and prognostic values of fibronectin and integrin αvβ3 expression in primary osteosarcoma.

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