Development and Validation of a Liquid-Liquid Phase Separation-Related Gene Signature as Prognostic Biomarker for Low-Grade Gliomas.

Aim: To explore whether the liquid-liquid phase separation- (LLPS-) related genes were potential prognostic markers that could contribute to the further classification of low-grade gliomas (LGGs). Methods: The LLPS-related genes were subjected to functional enrichment analysis. The univariable, least absolute shrinkage and selection operator, and multivariable stepwise Cox regression analyses were performed to develop an LLPS-related gene signature (GS) in the discovery data set. The biological characteristics of the high-risk LGG were explored using gene set enrichment analysis. Two independent external data sets were used to validate the LLPS-related GS. Results: LLPS-related genes are involved in multiple important cancer-related biological processes and pathways in LGG. Nine LLPS-related genes were identified to construct the LLPS-related GS, which was significantly associated with the prognosis of LGG patients. The LLPS-related GS could successfully divide patients with LGG into high- and low-risk groups, and the high-risk group showed a poorer prognosis than the low-risk group. Furthermore, the LLPS-related GS was independent of IDH and 1p19q status. Several cancer-related pathways may be more active in high-risk LGGs, such as IL6 JAK STAT3 signaling pathway. The LLPS-related GS was successfully validated with two independent external data sets. Conclusion: We developed and validated a novel LLPS-related GS for risk stratification of LGG. Our findings may provide more precise management for LGGs and a useful reference for LLPS mechanism to link LGG studies.

Expression profile of ACTL8, CTCFL, OIP5 and XAGE3 in glioma and their prognostic significance: a retrospective clinical study.

BACKGROUND: Cancer/testis antigens (CTAs) are attractive therapeutic targets for tumor immunotherapy due to their restrictive expression in normal testis but excessive in majority of tumor types. ACTL8, CTCFL, OIP5 and XAGE3 are members of the CTAs family. Currently, the data of ACTL8, CTCFL, OIP5 and XAGE3 expression in glioma is limited. Methods: ACTL8, CTCFL, OIP5 and XAGE3 mRAN and protein expressions were detected in 108 glioma samples by Reverse Transcriptase-PCR (RT-PCR) and immunohistochemistry and the correlations between their expressions and clinical indexes were analyzed. Furthermore, their clinical significance on glioma prognosis was determined by follow-up data. Results: The mRNA positive rate of ACTL8, CTCFL, OIP5 and XAGE3 was 15.74% (17/108), 22.22% (24/108), 13.89% (15/108) and 37.96% (41/108), respectively. At least one CTA mRNA was expressed by 61.11% of glioma tissues, while 2 or more by 29.63%. For protein expression, the positive rate of them was 21.30% (23/108), 34.26% (37/108), 19.44% (21/108) and 23.15% (25/108), respectively. At least one CTA protein was expressed by 58.33% of glioma tissues and 2 or more by 29.63%. Although there were no correlations between their mRNA expressions and clinicopathological parameters, the protein expression of ACTL8, OIP5 and XAGE3 was positively correlated with KPS; while the ACTL8 protein was correlated with gender, and OIP5 protein with gender and WHO grade. Kaplan-Meier analysis revealed a significant negative correlation between the CTCFL protein expression, combined ACTL8 and/or CTCFL protein expression and survival. Conclusions: The results suggest that the cohort of glioma does express ACTL8, CTCFL, OIP5 and XAGE3 at both mRNA and protein levels indicating glioma is CTAs-rich tumors. CTCFL protein and the combined ACTL8 and/or CTCFL protein might act as poor prognostic markers for glioma and as potential ideal combined antigens for glioma immunotherapy.