Abstract
BackgroundDeregulation of integrins signaling had been documented to participate in multiple fundamental biological processes, and the aberrant expression of integrin family members were linked to the prognosis of various cancers. However, the role of integrins in predicting progression and prognosis of ovarian cancer patients are still largely elusive. This study is aimed to explore the prognostic values of ITGA and ITGB superfamily members in high grade serous ovarian cancers (HGSOC).MethodsGSE26712 dataset was used to determine the differential expression of ITGA and ITGB superfamily member between HGSOC and normal counterparts. The Cancer Genome Altas (TGGA) and GSE9891 datasets were used to determine the prognostic values of ITGA and ITGB superfamily members in HGSOC, followed by the development of nomograms predictive of recurrence free survival (RFS) and overall survival (OS).ResultsITGA6 and ITGB5 expression were significantly downregulated in HGSOC compared with that in normal counterparts. In contrast, ITGA2, ITGA5, ITGA7, ITGA8, ITGA9, ITGA10, ITGB3, ITGB4, ITGB6, and ITGB8 were all significantly upregulated in HGSOC compared with that in normal counterparts. Both univariable and multivariable analysis indicated that ITGB1 was associated with extended RFS. The ITGB1-related nomogram indicated that ITGB1 had the largest contribution to RFS, followed by FIGO stage and debulking status. The C-index for predicting RFS was 0.55 (95% CI 0.50–0.59) in TCGA dataset (training dataset) and 0.65 (95% CI 0.59–0.72) in GSE9891 dataset (validation dataset), respectively. Regarding OS, ITGB8 was associated with reduced survival suggested by both univariable and multivariable analysis. ITGA7 appeared to be associated with improved survival though without reaching statistical significance. The ITGA7/ITGB8-based nomogram showed that age at initial diagnosis had the largest contribution to OS, followed by ITGB8 and ITGA7 expression. The C-index for predicting OS was 0.65 (95% CI 0.60–0.69) in TCGA dataset (training dataset) and 0.59 (95% CI 0.51–0.66) in GSE9891 dataset (validation dataset), respectively.ConclusionIn conclusion, ITGB1, ITGA7 and ITGB8 added prognostic value to the traditional clinical risk factors used to assess the clinical outcomes of HGSOC.
Highlights
Deregulation of integrins signaling had been documented to participate in multiple fundamental biological processes, and the aberrant expression of integrin family members were linked to the prognosis of various cancers
The prognostic value of ITGA and ITGB members for recurrence free survival (RFS) in high grade serous ovarian cancers (HGSOC) we determined the prognostic significance of ITGA and ITGB members in predicting RFS in patients with HGSOC using TCGA dataset (Table 1)
Both univariable and multivariable analysis indicated that ITGB1 and ITGB8 was an independent predictor of RFS and overall survival (OS) in HGSOC, respectively
Summary
Deregulation of integrins signaling had been documented to participate in multiple fundamental biological processes, and the aberrant expression of integrin family members were linked to the prognosis of various cancers. The role of integrins in predicting progression and prognosis of ovarian cancer patients are still largely elusive. This study is aimed to explore the prognostic values of ITGA and ITGB superfamily members in high grade serous ovarian cancers (HGSOC). High grade serous ovarian cancer (HGSOC) is an aggressive and incurable malignancy and most patients with newly diagnosed HGSOC presented with advanced stage [1]. In the era of precision medicine, an improved understanding of the molecular features of ovarian cancer had led to better stratification of the patient prognosis and subsequent identification of novel therapeutic targets [4]. Some patients with HGSOC still had a poor prognosis despite of novel treatments [8]. It is important to identify new biomarkers to predict HGSOC prognosis, which will subsequently facilitate the development of new personalized treatment strategies [4]
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