ABSTRACT
The expression of estrogen receptor alpha (ERα, encoded by ESR1) has been shown to be associated with the prognostic outcomes of patients in various cancers; however, its prognostic and mechanistic significance in hepatocellular carcinoma (HCC) remain unclear. Here, we evaluated the expression of ERα and its association with clinicopathological features in 339 HCC patients. ERα was expressed in 9.4% (32/339) of HCCs and was related to better overall survival (OS; hazard ratio [HR] = 0.11, p = 0.009, 95% C.I. = 0.016-0.82) and disease-free survival (DFS, HR = 0.4, p = 0.013, 95% C.I. = 0.18-0.85). ERα expression was also associated with features related to more favorable prognosis, such as older age, lower serum alpha-fetoprotein level, and less microvascular invasion (p < 0.05). In addition, to obtain mechanistic insights into the role of ERα in HCC progression, we performed integrative transcriptome data analyses, which revealed that yes-associated protein (YAP) pathway was significantly suppressed in ESR1-expressing HCCs. By performing cell culture experiments, we validated that ERα expression enhanced YAP phosphorylation, attenuating its nuclear translocation, which in turn suppressed the downstream signaling pathways and cancer cell growth. In conclusion, we suggest that ERα expression is an indicator of more favorable prognosis in HCC and that this effect is mediated by inactivation of YAP signaling. Our results provide new clinical and pathobiological insights into ERα and YAP signaling in HCC.
Subject(s)
Carcinoma, Hepatocellular , Cell Cycle Proteins/metabolism , Liver Neoplasms , Transcription Factors/metabolism , Carcinoma, Hepatocellular/metabolism , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Humans , Liver Neoplasms/metabolism , Phosphorylation , Signal TransductionABSTRACT
Involvement of central nervous system occasionally occurs as a form of aseptic meningitis in Kikuchi-Fujimoto disease (KFD). However, acute cerebellar symptoms are very rare in KFD. We describe a 42 year-old woman presenting kinetic tremor and gait ataxia preceding cervical lymphadenopathy. The diagnosis of KFD was made based on pathology. Lymphocyte-dominant pleocytosis was observed in cerebrospinal fluid. Brain and spinal magnetic resonance imaging showed no structural abnormalities. Acute cerebellar symptoms and cervical lymphadenopathy disappeared spontaneously within 2 months. This case of KFD involved unusual acute cerebellar symptoms. Selective involvement of the cerebellar system by viral or immunologic response may be attributed to acute cerebellar symptoms in KFD.