PO.MCB10.01 · 分子与细胞生物学
microRNA编码基因特征在妇科癌症中的预后潜力
Prognostic potential of microRNA-encoding gene signatures in gynecologic cancers
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景/意义：为改善妇科癌症的预后，需要有效的早期生物标志物。microRNA（miRNA）是小的非编码RNA，在转录后基因调控中发挥作用，其功能失调可在癌症发生和进展中起关键作用。近年来，miRNA作为多种恶性肿瘤的循环生物标志物的作用日益受到关注。然而，针对高死亡率妇科癌症（如卵巢浆液性囊腺癌（OV）、子宫内膜癌（UCEC）和子宫癌肉瘤（UCS））的研究仍存在空白。本研究的目的是利用癌症基因组图谱（TCGA）数据集，分析选定的miRNA编码基因（如hsa-mir-6511b-1、hsa-mir-6820和hsa-mir-3198-2）在OV、UCEC和UCS癌症患者肿瘤标本中的表达谱。此外，我们通过将这些miRNA的表达水平与总生存期和临床结局相关联，评估了其预后意义。
方法：数据取自TCGA，一个用于分析肿瘤基因和生存曲线的在线门户。对OV与UCS、OV与UCEC、UCS与UCEC之间的共同miRNA编码基因进行了比较。获得了OV（n=474）与UCS（n=56）的生存曲线。临床试验信息通过clinicaltrials.gov获取。数据经分析后，统计学显著性通过Student's t检验（两组间比较）或单因素方差分析（多组间比较）评估，生存曲线采用Kaplan-Meier法结合log-rank检验分析。p值≤0.05被视为具有显著性。
结果：分析揭示了基于所关注的miRNA编码基因hsa-mir-6511b-1、hsa-mir-6820和hsa-mir-3198-2表达的患者生存差异，涉及OV和UCS。hsa-mir-6511b-1的高表达在OV（p=0.021）和UCS（p=0.035）患者中均与较短生存期相关。相反，hsa-mir-6820的高表达显示出相反的效应：在OV患者中与较短生存期相关（p=0.024），但在UCS患者中与较长生存期相关（p=0.028）。hsa-mir-3198-2的高表达在OV（p=0.027）和UCS（p=0.046）患者中均与较长生存期相关。数据提示miRNA在这些妇科癌症中的作用似乎复杂，同时显示出致癌和保护性效应。
结论：这些初步发现强调miRNA在妇科癌症中以情境依赖的方式发挥作用。应进一步研究miRNA的重要性，以验证其作为早期检测、预后和治疗策略生物标志物的潜力。本实验室正在开展转化研究，以精确理解miRNA编码基因对耐药性的作用，从而解决妇科癌症模型中的铂类耐药问题。
查看英文原文 English abstract
Background/Significance: Effective early-stage biomarkers are needed for improving outcomes in gynecologic cancers. Micro RNAs (miRNAs) are small non-coding RNAs that function in post-transcriptional gene regulation and their dysfunction can play key role in cancer development and progression. Recently, the role of miRNAs is gaining attention as circulating biomarkers for various malignancies. However, there is a gap in studies involving gynecologic cancers with high-mortality rates such as ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), and uterine carcinosarcoma (UCS). The objectives of this study are to analyze the expression profiles of selected miRNA-coding genes such as hsa-mir-6511b-1, hsa-mir-6820, and hsa-mir-3198-2 in tumor specimens from patients with OV, UCEC, and UCS cancers using The Cancer Genome Atlas (TCGA) datasets. Additionally, we evaluated the prognostic significance of these miRNAs by correlating their expression levels with overall survival and clinical outcomes.
Methods: Data were obtained from TCGA, an online portal for analyzing tumor genes and survival curves. A comparison was made between the common miRNA-coding genes in OV vs UCS, OV vs UCEC, and UCS vs UCEC. Survival curves were obtained for OV (n=474) vs UCS (n=56). Clinical trials information was accessed through clinicaltrials.gov. Data was analyzed and the statistical significance was assessed by Student's t-test (comparisons between two-groups), or one-way ANOVA (for multiple-groups), and survival curves were analyzed using Kaplan-Meier method with log-rank test. A p-value of 0.05 or less was considered significant.
Results: Analyses revealed differences in patient survival based on the expression of the miRNA-coding genes of interest, hsa-mir-6511b-1, hsa-mir-6820, and hsa-mir-3198-2, in OV and UCS. High expression of hsa-mir-6511b-1 was associated with a shorter survival period in both OV (p=0.021) and UCS (p=0.035) patients. In contrast, high expression of hsa-mir-6820 showed opposite effects: it was linked to shorter survival in OV patients (p=0.024) but longer survival in UCS patients (p=0.028). High expression of hsa-mir-3198-2 was associated with longer survival in both OV (p=0.027) and UCS (p=0.046) patients. Data suggest that the role of miRNAs in these gynecologic cancers appears to be complex, showing both oncogenic and protective effects.
Conclusions: These preliminary findings emphasize that miRNAs behave in a context-dependent manner in gynecologic cancers. Importance of miRNAs should be further studied to validate their potential as biomarkers for early detection, prognosis, and treatment strategies. Our laboratory is conducting translational studies to precisely understand the role of miRNA-coding genes on drug resistance to address platinum-resistance in gynecologic cancer models.
利益披露 Disclosure
E. Miller, None..
A. Hoskins, None..
N. Gierat, None..
R. Basha, None.