Haque Razaul, Lee Jaebon, Chung Joon-Yong, Shin Ha-Yeon, Kim Hyosun, Kim Jae-Hoon, Yun Jae Won, Kang Eun-Suk
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Seoul, Republic of Korea.
School of Medicine, Sungkyunkwan University, Suwon, Republic of Korea.
Front Oncol. 2023 Jun 5;13:1152991. doi: 10.3389/fonc.2023.1152991. eCollection 2023.
BACKGROUND/OBJECTIVE: High-grade serous ovarian carcinoma (HGSOC) is the most common histologic type of epithelial ovarian cancer (EOC). Due to its poor survival outcomes, it is essential to identify novel biomarkers and therapeutic targets. The hippo pathway is crucial in various cancers, including gynaecological cancers. Herein, we examined the expression of the key genes of the hippo pathway and their relationship with clinicopathological significance, immune cells infiltration and the prognosis of HGSOC.
The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data were curated to analyse the mRNA expression as well as the clinicopathological association and correlation with immune cell infiltration in HGSOC. The protein levels of significant genes in the HGSOC tissue were analysed using Tissue Microarray (TMA)-based immunohistochemistry. Finally, DEGs pathway analysis was performed to find the signalling pathways associated with VGLL3.
VGLL3 mRNA expression was significantly correlated with both advanced tumor stage and poor overall survival (OS) (p=0.046 and p=0.003, respectively). The result of IHC analysis also supported the association of VGLL3 protein with poor OS. Further, VGLL3 expression was significantly associated with tumor infiltrating macrophages. VGLL3 expression and macrophages infiltration were both found to be independent prognostic factors (p=0.003 and p=0.024, respectively) for HGSOC. VGLL3 was associated with four known and three novel cancer-related signalling pathways, thus implying that VGLL3 is involved in the deregulation of many genes and pathways.
Our study revealed that VGLL3 may play a distinct role in clinical outcomes and immune cell infiltration in patients with HGSOC and that it could potentially be a prognostic marker of EOC.
背景/目的：高级别浆液性卵巢癌（HGSOC）是上皮性卵巢癌（EOC）最常见的组织学类型。由于其生存结果较差，识别新的生物标志物和治疗靶点至关重要。河马通路在包括妇科癌症在内的各种癌症中都起着关键作用。在此，我们研究了河马通路关键基因的表达及其与HGSOC临床病理意义、免疫细胞浸润和预后的关系。
整理癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的数据，以分析HGSOC中的mRNA表达以及临床病理关联和与免疫细胞浸润的相关性。使用基于组织微阵列（TMA）的免疫组织化学分析HGSOC组织中重要基因的蛋白质水平。最后，进行差异表达基因（DEG）通路分析以找到与VGLL3相关的信号通路。
VGLL3 mRNA表达与晚期肿瘤分期和较差的总生存期（OS）均显著相关（分别为p = 0.046和p = 0.003）。免疫组织化学分析结果也支持VGLL3蛋白与较差的OS相关。此外，VGLL3表达与肿瘤浸润巨噬细胞显著相关。VGLL3表达和巨噬细胞浸润均被发现是HGSOC的独立预后因素（分别为p = 0.003和p = 0.024）。VGLL3与四个已知和三个新的癌症相关信号通路相关，这意味着VGLL3参与了许多基因和通路的失调。
我们的研究表明，VGLL3可能在HGSOC患者的临床结果和免疫细胞浸润中发挥独特作用，并且它可能是EOC的一个预后标志物。
