Yamada Hideharu, Takahashi Masanobu, Watanuki Munenori, Watanabe Mika, Hiraide Sakura, Saijo Ken, Komine Keigo, Ishioka Chikashi
Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
Department of Medical Oncology, Tohoku University Hospital, Sendai, Miyagi 980-8574, Japan.
Oncol Lett. 2021 Jun;21(6):455. doi: 10.3892/ol.2021.12716. Epub 2021 Apr 8.
Bone and soft-tissue sarcomas are rare and are highly heterogeneous mesenchymal malignancies. It is therefore challenging to acquire the clinical data of patients with specific histological subtypes of sarcoma using large clinical trials, and there is a need to further establish the diagnosis and treatment of sarcomas. The results of the current study revealed that long non-coding RNA (lncRNA) highly accelerated region 1B () may serve as a predictive biomarker for pazopanib treatment in bone and soft-tissue sarcomas. Using multiplex reverse transcription-quantitative PCR and microarray analyses, the results demonstrated that and HOX transcript antisense RNA () were differentially expressed in pazopanib-sensitive cells and responders. It was further revealed that small interfering RNA-knockdown of led to an increased resistance to pazopanib in sarcoma cell lines. Gene expression profiles associated with pazopanib sensitivity included cellular molecular pathways, such as genes involved in von-Willebrand factor-related signaling. The current study demonstrated that lncRNA expression in sarcoma cell lines affected cellular sensitivity to pazopanib in patients with sarcoma.
骨肉瘤和软组织肉瘤较为罕见，是高度异质性的间充质恶性肿瘤。因此，通过大型临床试验获取特定组织学亚型肉瘤患者的临床数据具有挑战性，有必要进一步确立肉瘤的诊断和治疗方法。当前研究结果显示，长链非编码RNA（lncRNA）高加速区域1B（）可能作为骨肉瘤和软组织肉瘤中帕唑帕尼治疗的预测生物标志物。通过多重逆转录定量PCR和微阵列分析，结果表明在帕唑帕尼敏感细胞和有反应者中，和HOX转录本反义RNA（）存在差异表达。进一步研究发现，小干扰RNA敲低在肉瘤细胞系中导致对帕唑帕尼的耐药性增加。与帕唑帕尼敏感性相关的基因表达谱包括细胞分子途径，如参与血管性血友病因子相关信号传导的基因。当前研究表明，肉瘤细胞系中lncRNA的表达影响肉瘤患者对帕唑帕尼的细胞敏感性。
