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Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome.

ABSTRACT: Integrins are cell-extracellular matrix adhesion molecules whose expression level undergoes quantitative changes upon neoplastic transformation and are considered functionally related to the development of cancer metastasis. We analyzed the largest mRNA-seq dataset available to determine the expression pattern of integrin family subunits in papillary thyroid carcinomas (PTC). ITGA2, 3, 6, V, and ITGB1 integrin subunits were overexpressed in PTC compared to normal thyroid tissue. The PTC histology variants "classical" and "tall cell" displayed a similar integrin expression profile with a higher level of ITGA3, ITGAV, and ITGB1, which differed from that of the "follicular" variant. Interestingly, compared to RAS mutations, BRAFV600E mutation was associated with a significantly higher expression of integrins. Some integrin subunits were associated with advanced disease stage, lymph node metastasis, extrathyroidal extension, and high-risk groups. Among them, ITGA3 expression displayed the highest correlation with advanced disease and was associated with a negative prognosis. In vitro scratch assay and Matrigel invasion assay in two different PTC cell lines confirmed α3β1 role in cell motility and invasion, supporting its involvement during tumor progression. These results demonstrate the existence of a PTC-specific integrin expression signature correlated to histopathology, specific driver gene mutations, and aggressiveness of the disease.

SUBMITTER: Mautone L

PROVIDER: S-EPMC8230752 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionPapillary thyroid carcinoma is a type of thyroid cancer that exhibits significant variability in prognosis. Extensive research indicates that the impaired signaling of 1,25(OH)2D3-VDR may be a crucial factor in the development and progression of PTC.MethodsTo investigate this further, Integrated analysis mRNA expression information from The Cancer Genome Atlas and GEO, we compared gene expression in cancer and normal tissues and identified differentially expressed genes (DEGs). Through this analysis, we identified DEGs and calculated risk estimates for seven genetic markers.ResultsSubsequently, we constructed predictive models using LASSO-Cox regression to test the predictive value of these markers. Our results revealed that 64 calcium metabolism-related genes showed significant differences between tumor and normal tissues. Ten of the identified DEGs were significantly associated with overall survival, indicating their potential role in disease progression. Using the average risk score for the seven genetic markers, we divided patients into high- and low-risk groups. We found that patients in the low-risk group had significantly better overall survival than those in the high-risk group, highlighting the importance of these genetic markers in predicting prognosis. Further analysis using Cox regression demonstrated that the risk levels had independent predictive power. Additionally, we conducted functional analysis of the identified genetic markers, which showed significant differences in immune status between the two patient groups. We also investigated the effect of these calcium metabolism-related genes on thyroid cancer biological functions, immune microenvironment, and drug resistance.DiscussionOur findings provide evidence of a novel genetic signature associated with calcium metabolism, which can predict prognosis in patients with PTC. These results may have significant implications for the development of new diagnostic and therapeutic approaches to improve outcomes for PTC patients.

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Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome.

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