Expression and clinical implications of leucine-rich repeat containing 15 (LRRC15) in osteosarcoma
Expression and clinical implications of leucine-rich repeat containing 15 (LRRC15) in osteosarcoma
复制标题
DOI：
10.1002/jor.24848
复制
发表时间：
2020-09-19
影响因子：
2.8
通讯作者：
Duan, Zhenfeng
中科院分区：
文献类型：
--
作者：
Cui, Juncheng;Dean, Dylan;Duan, Zhenfeng
富含亮氨酸重复序列15 （Leucine-rich repeat containing 15, LRRC15）是富含亮氨酸重复序列超家族的成员，在多种癌症中过表达，与较高的肿瘤分级和侵袭性相关。尽管已知其致瘤性，但其在骨肉瘤中的作用尚不清楚，这促使我们评估其在这种罕见但侵袭性癌症中的表达和临床意义。Western blot结果显示LRRC15在骨肉瘤细胞系MNNG/HOS、KHOS、143B、MG63、Saos-2和U2OS中的表达存在差异。我们还用免疫荧光验证了这种阳性表达，以及亚定位到细胞膜上。从69例骨肉瘤患者组织中构建组织微阵列，免疫组织化学染色检测LRRC15表达，分层，并用于临床病理分析。公开的LRRC15表达数据库，包括来自骨肉瘤治疗应用研究（TARGET-OS）和正常和肿瘤组织基因表达数据库2 （GENT2）的RNA测序数据。我们发现69例患者组织中有63例（91.3%）表现出一定程度的LRRC15免疫染色，包括未染色（69例中6例，8.7%）、1+染色（69例中12例，17.4%）、2+染色（69例中25例，36.2%）和3+染色（69例中26例，37.7%）。LRRC15表达升高的骨肉瘤患者转移、化疗耐药相对增加，5年生存率较短。我们对TARGET-OS和GENT2数据库的分析也显示LRRC15基因在骨肉瘤中的表达增加。综上所述，我们的研究支持LRRC15作为骨肉瘤的预后生物标志物和新兴治疗靶点。
Leucine-rich repeat containing 15 (LRRC15) is a member of the leucine-rich repeat superfamily that is overexpressed in various cancers and associated with higher tumor grade and aggression. Despite its known tumorigenicity, its roles within osteosarcoma are unknown, prompting us to evaluate its expression and clinical significance within this rare yet aggressive cancer. Western blots showed differential expression of LRRC15 in the osteosarcoma cell lines MNNG/HOS, KHOS, 143B, MG63, Saos-2, and U2OS. We additionally validated this positive expression, as well as sublocalization to the cell membrane, with immunofluorescence. A tissue microarray constructed from 69 osteosarcoma patient tissues was immunohistochemically stained for LRRC15 expression, stratified, and used for clinicopathological analysis. Publicly available databases on LRRC15 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2) were also analyzed. We found 63 of the 69 (91.3%) patient tissues exhibited some degree of LRRC15 immunostaining, including no staining (6 of 69, 8.7%), 1+ staining (12 of 69, 17.4%), 2+ staining (25 of 69, 36.2%), and 3+ staining (26 of 69, 37.7%). The patients with osteosarcomas having elevated LRRC15 expression demonstrated comparatively increased metastasis, chemoresistance, and shorter 5-year survival rates. Our analysis of the TARGET-OS and GENT2 databases also showed increased LRRC15 gene expression in osteosarcoma. Taken together, our study supports LRRC15 as a prognostic biomarker and emerging therapeutic target in osteosarcoma.