Present Address: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, No.419, Fangxie Road, Shanghai, 200011, People's Republic of China.
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China.
J Ovarian Res. 2021 Nov 22;14(1):166. doi: 10.1186/s13048-021-00915-9.
Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients.
The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset.
We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status.
In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.
淋巴血管空间侵犯（LVSI）是血行转移的第一步。探索 LVSI 阳性和 LVSI 阴性卵巢癌组织之间差异表达的 miRNA 图谱，可能有助于鉴定涉及卵巢癌血行转移的关键 miRNA。本研究旨在鉴定 LVSI 阳性和 LVSI 阴性卵巢癌组织之间差异表达的 microRNAs（miRNAs），并进一步探讨其与卵巢癌患者对贝伐珠单抗反应的关系。
使用癌症基因组图谱（TCGA）数据集鉴定 LVSI 阳性和 LVSI 阴性卵巢癌组织之间差异表达的 miRNAs。使用 GSE140082 数据集确定差异表达 miRNAs 的预后价值。
我们发现 miR-25 和 miR-142 在 LVSI 阳性和 LVSI 阴性卵巢癌肿瘤之间差异表达。Kaplan-Meier 分析表明，高 miR-25 表达与无进展生存期（PFS）延长和总生存期（OS）延长相关。此外，miR-25 低表达的患者在 PFS 方面从贝伐珠单抗治疗中获益显著。OS 也观察到类似的趋势，但没有达到统计学意义。相反，在 PFS 和 OS 方面，高 miR-25 表达的患者从贝伐珠单抗治疗中没有显著的生存获益。miR-142 表达与 PFS 之间没有显著相关性。相反，高 miR-142 表达与 OS 降低相关。此外，miR-142 高表达的患者在 PFS 和 OS 方面从贝伐珠单抗治疗中获益显著。然而，miR-142 低表达的患者接受贝伐珠单抗治疗在 PFS 和 OS 方面均无显著改善。PFS 列线图表明，miR-25 表达对 PFS 的贡献大于肿瘤减灭术状态和贝伐珠单抗治疗。OS 列线图表明，miR-25 表达和 miR-142 表达与贝伐珠单抗治疗和肿瘤减灭术状态相比，对 OS 的贡献更大。
总之，miR-25 表达与卵巢癌患者的 PFS 和 OS 相关。miR-25 低表达和 miR-142 高表达的患者可显著从贝伐珠单抗治疗中获益。
