Abstract
Human integrin receptors are important for cell-cell and cell-matrix adhesion in normal epithelial cells. Emerging evidences have indicated integrin members are involved in cancer development and progression as well. However, the expression patterns and clinical significance of the whole integrin family in ovarian cancer (OC) have not yet been well understood. In the present study, we utilized the public datasets including GEPIA, GEO, ONCOMINE, cBioPortal, Kaplan-Meier Plotter, TIMER databases, to analyze the expression and prognostic value of integrin members in OC. We found ITGA3/B4/B6/B7/B8 were abnormally overexpressed in OC; ITGA6 was good prognosis predictor in OC; ITGA3/ B4/B8 were poor prognosis predictor specially in advanced OC patients; elevated ITGA3/B4 might promote metastasis and elevated ITGA3/B8 might promote platinum resistance of OC; ITGA3 and ITGB4 might synergistically or independently regulate cell adhesion and proliferation; ITGA4/AL/AM/AX/B2/B7 showed strong correlations with various tumor immune infiltrates (TILs), especially with pro-tumor immunes cell types like monocyte, M2 macrophage and exhaustion T cells infiltration; ITGAL/AM/B2/B7 and residing memory CD8+ T cells marker ITGAE were specially associated with early OC patients outcome. Our results implied that ITGA3/B4 were important prognostic markers of advanced OC, ITGAL/AM/ B2/B7 were immune associated prognosis markers of early OC, together they might render important therapeutic targets for OC.
Highlights
Ovarian cancer (OC) as the most lethal gynecological cancer, its mortality rate ranks fifth in female’s death associated with cancer (Siegel et al, 2019)
The results indicated that ITGA3 and ITGB2/B4/B5/B6/B7/B8 transcriptional levels were significantly higher in ovarian cancer (OC) samples than in normal ovary tissue, while ITGA5/A7/A8/A10 expression levels were significantly lower and other integrins showed no statistic differences (Figure 1A)
This study demonstrates that the ITGA3 and ITGB4/B6/B7/B8 are highly expressed in OC when compared to normal ovary tissues
Summary
Ovarian cancer (OC) as the most lethal gynecological cancer, its mortality rate ranks fifth in female’s death associated with cancer (Siegel et al, 2019). Patients diagnosed with OC are at a median age of around 60 years, and majority of them are diagnosed at advanced stages, with companion of metastasis. Lacking of effective early stage detection greatly contributes the poor survival rate of OC. Surgical debulking and platinum-based chemotherapy are the first-line therapy strategy for OC treatment. Most patients show good responses to chemotherapy for the first time, recurrence probably develop within 18 months, and eventually result in succumbing to cancer (Jayson et al, 2014; Torre et al, 2018; Lheureux et al, 2019).
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