The prognostic value of ITGA and ITGB superfamily members in patients with high grade serous ovarian cancer.

ABSTRACT

BACKGROUND: 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. 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). METHODS: GSE26712 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). RESULTS: ITGA6 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. CONCLUSION: In conclusion, ITGB1, ITGA7 and ITGB8 added prognostic value to the traditional clinical risk factors used to assess the clinical outcomes of HGSOC.