Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA 52245, USA.
Department of Gynecologic Oncology, University of Buffalo, Buffalo, NY 14203, USA.
Int J Mol Sci. 2021 Jan 22;22(3):1079. doi: 10.3390/ijms22031079.
Long non-coding RNA's (lncRNA) are RNA sequences that do not encode proteins and are greater than 200 nucleotides in length. They regulate complex cellular mechanisms and have been associated with prognosis in various types of cancer. We aimed to identify lncRNA sequences that are associated with high grade serous ovarian cancer (HGSC) and assess their impact on overall survival. RNA was extracted from 112 HGSC patients and 12 normal fallopian tube samples from our Biobank tissue repository. RNA was sequenced and the Ultrafast and Comprehensive lncRNA detection and quantification pipeline (UClncR) was used for the identification of lncRNA sequences. Univariate logistic and multivariate lasso regression analyses identified lncRNA that was associated with HGSC. Univariate and multivariate Cox proportional hazard ratios were used to evaluate independent predictors of survival. 1943 of 16,325 investigated lncRNA's were differentially expressed in HGSC as compared to controls ( < 0.001). Nine of these demonstrated association with cancer after multivariate lasso regression. Our multivariate analysis of survival identified four lncRNA's associated with survival in HGSC. Three out of these four were found to be independently significant after accounting for all clinical covariates. Lastly, seven lncRNAs were independently associated with initial response to chemotherapy; four portended a worse response, while three were associated with improved response. More research is needed, but there is potential for these lncRNAs to be used as biomarkers of HGSC or predictors of treatment outcome in the future.
长链非编码 RNA（lncRNA）是指不编码蛋白质且长度大于 200 个核苷酸的 RNA 序列。它们调节复杂的细胞机制，并与各种类型癌症的预后相关。我们旨在鉴定与高级别浆液性卵巢癌（HGSC）相关的 lncRNA 序列，并评估其对总生存期的影响。从我们的生物库组织库中提取了 112 例 HGSC 患者和 12 例正常输卵管样本的 RNA。对 RNA 进行测序，并使用 Ultrafast 和 Comprehensive lncRNA detection and quantification pipeline (UClncR) 鉴定 lncRNA 序列。单变量逻辑回归和多变量lasso 回归分析确定了与 HGSC 相关的 lncRNA。单变量和多变量 Cox 比例风险比用于评估生存的独立预测因子。与对照组相比，在 HGSC 中，16325 个研究的 lncRNA 中有 1943 个表达差异（<0.001）。在多变量 lasso 回归后，其中 9 个显示与癌症相关。我们对 HGSC 生存的多变量分析确定了与生存相关的四个 lncRNA。在考虑所有临床协变量后，这四个中有三个被发现具有独立意义。最后，有七个 lncRNA 与初始化疗反应独立相关；四个预示着反应较差，三个与改善的反应相关。需要进一步研究，但这些 lncRNA 有可能在未来被用作 HGSC 的生物标志物或治疗结果的预测因子。
