Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Harbin Medical University, Harbin, China.
HMU-UCCSM Centre for Infection and Genomics, Harbin Medical University, Harbin, China.
BMC Cancer. 2022 Jun 16;22(1):662. doi: 10.1186/s12885-022-09747-2.
Ovarian cancer (OC) is among the deadliest malignancies in women and the lack of appropriate markers for early diagnosis leads to poor prognosis in most cases. Previous studies have shown that KAZN is involved in multiple biological processes during development, such as cell proliferation, differentiation, and apoptosis, so defects or aberrant expression of KAZN might cause queer cell behaviors such as malignancy. Here we evaluated the KAZN expression and methylation levels for possible use as an early diagnosis marker for OC.
We used data from Gene Expression Omnibus (GEO) microarrays, The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to investigate the correlations between KAZN expression and clinical characteristics of OC by comparing methylation levels of normal and OC samples. The relationships among differentially methylated sites in the KAZN gene, corresponding KAZN mRNA expression levels and prognosis were analyzed.
KAZN was up-regulated in ovarian epithelial tumors and the expression of KAZN was correlated with the patients' survival time. KAZN CpG site cg17657618 was positively correlated with the expression of mRNA and the methylation levels were significantly differential between the group of stage "I and II" and the group of stage "III and IV". This study also presents a new method to classify tumor and normal tissue in OC using DNA methylation pattern in the KAZN gene body region.
KAZN was involved in ovarian cancer pathogenesis. Our results demonstrate a new direction for ovarian cancer research and provide a potential diagnostic biomarker as well as a novel therapeutic target for clinical application.
卵巢癌（OC）是女性最致命的恶性肿瘤之一，由于缺乏早期诊断的适当标志物，大多数情况下预后较差。先前的研究表明，KAZN 参与了发育过程中的多种生物学过程，如细胞增殖、分化和凋亡，因此 KAZN 的缺陷或异常表达可能导致异常细胞行为，如恶性肿瘤。在这里，我们评估了 KAZN 的表达和甲基化水平，以期将其用作 OC 的早期诊断标志物。
我们使用来自基因表达综合数据库（GEO）微阵列、癌症基因组图谱（TCGA）和临床蛋白质组肿瘤分析联盟（CPTAC）的数据，通过比较正常和 OC 样本的甲基化水平，研究 KAZN 表达与 OC 临床特征之间的相关性。分析了 KAZN 基因中差异甲基化位点与相应 KAZN mRNA 表达水平和预后之间的关系。
KAZN 在卵巢上皮性肿瘤中上调，并且 KAZN 的表达与患者的生存时间相关。KAZN CpG 位点 cg17657618 与 mRNA 的表达呈正相关，其甲基化水平在“I 期和 II 期”组和“III 期和 IV 期”组之间存在显著差异。本研究还提出了一种使用 KAZN 基因体区域的 DNA 甲基化模式对 OC 中的肿瘤和正常组织进行分类的新方法。
KAZN 参与了卵巢癌的发病机制。我们的结果为卵巢癌研究提供了一个新的方向，并为临床应用提供了一个潜在的诊断生物标志物和一个新的治疗靶点。
