Background: Large tumor suppressor (LATS) proteins are putative tumor suppressors and poorly expressed associated with poor outcome in many cancers. A recent immunohistochemistry study showed that LATS protein expression correlated with poor outcome in serous ovarian cancer.
Materials and methods: We analyzed LATS expression in various ovarian cancer transcriptomic data sets and immunohistochemically assessed LATS protein expression in a Swiss ovarian tumor cohort. Results were compared to clinicopathological characteristics and outcome. We also compared LATS protein expression in serous ovarian cancer cell lines to their EMT status (Western blotting) and drug sensitivity (MTT assay).
Results: The analysis of 15 different transcriptomic data sets showed that LATS2 was associated with poorer outcome, while LATS1 was irrelevant (HR = 1.19 and HR = 1.00, respectively). The TCGA-RNASeqV2 data set showed that low LATS1 and LATS2 were associated with better survival in serous ovarian carcinoma. Despite heterogeneity among the different data sets, LATS expression is not an indicator of survival in serous ovarian cancer and LATS2 expression may even be tumorigenic. LATS expression was neither associated with survival nor with the stage and grade in the Swiss cohort. It was low in cystadenoma, intermediate in carcinoma, and high in borderline tumors and was higher in serous than mucinous ovarian carcinoma. LATS protein expression extent was comparable in epithelial-, intermediate-, and mesenchymal-type ovarian cancer cells and was not associated with drug sensitivity.
Conclusion: These results are largely incompatible with a tumor-suppressive function of LATS in ovarian cancer, and LATS protein level is also not an indicator for drug sensitivity and EMT status of ovarian cancer cells.
Keywords: Drug sensitivity; Epithelial–mesenchymal transition (EMT); Large tumor suppressor (LATS); Outcome; Ovarian cancer; Transcriptomics.