Department of Geriatric Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, 710061, People's Republic of China.
Department of Oncology Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, 710061, People's Republic of China.
BMC Cancer. 2019 Mar 13;19(1):227. doi: 10.1186/s12885-019-5406-x.
Gastric cancer (GC) is one of the most commonly occuring gastrointestinal tumor types, and early diagnosis and operation have a notable effect on the prognosis of patients. Although certain markers, including HER2, VEGER-2, ERCC1 and Bcl-2, have been utilized in clinical practise to screen out new patients with GC, the results of using these markers remains poor. The role of olfactomedin-like 2B (OLFML2B) in GC, as a member of the olfactomedin domain-containing proteins family, is remain unclear.
In the present study, we assessed the expression of OLFML2B, including mRNA and protein level, by using The Cancer Genome Atlas (TCGA) database and 13 pairs of clinical samples between GC and NG tissues. The correlation between expression of OLFML2B and prognosis of GC was evaculated by the Kaplan-Meier plotter and OncoLnc online tools. In addition, mechanism analysis of OLFML2B in GC was explored thought bioinformatic tools, including cBioPortal and FunRich software.
In our study, the mRNA expression of OLFML2B in GC both TCGA database and clinical samples was consistently revealed to be significantly higher compared with that in NG tissues (P < 0.0001 for TCGA database and P = 0.0034 for clinical samples), and high OLFML2B expression was found in 9 (69.23%) of 13 clinical GC by immunohistochemistry and was positively correlated with the depth of tumor invasion and clinical stage (TNM). In addition, the AUC for a ROC of 0.867 indicated a moderate diagnostic ability of OLFML2B for GC. Survival analysis from the Kaplan-Meier plotter (P = 2.6 × 10) and OncoLnc (P = 0.00276) revealed that the high expression of OLFML2B was associated with a short overall survival. Futhermore, 5% (24/478) alterations of OLFML2B were identified from cBioPortal, and among them, missense mutation (14/478) was the primary type. The results from FunRich revealed that OLFML2B participated in mediating multiple biological processes including cell growth and maintenance, regulation of the cell cycle, apoptosis and cell communication through multiple signaling pathways including the M/G1 transition pathway, post-translational protein modification and DNA replication pre-initiation.
Taken together, it could be deduced that OLFML2B may act as an oncogene in the development of GC and the overexpression of OLFML2B in GC may be used as a novel diagnostic and prognostic target for GC.
胃癌（GC）是最常见的胃肠道肿瘤类型之一，早期诊断和手术对患者的预后有显著影响。尽管某些标志物，包括 HER2、VEGER-2、ERCC1 和 Bcl-2，已被用于临床筛选新的 GC 患者，但这些标志物的应用效果仍不理想。嗅球蛋白样 2B（OLFML2B）作为嗅球蛋白域蛋白家族的成员，在 GC 中的作用尚不清楚。
本研究通过癌症基因组图谱（TCGA）数据库和 13 对 GC 和 NG 组织的临床样本评估了 OLFML2B 的表达，包括 mRNA 和蛋白水平。Kaplan-Meier plotter 和 OncoLnc 在线工具评估了 OLFML2B 表达与 GC 预后的相关性。此外，还通过 cBioPortal 和 FunRich 软件等生物信息学工具探索了 OLFML2B 在 GC 中的作用机制。
在本研究中，我们发现 OLFML2B 的 mRNA 表达在 TCGA 数据库和临床样本中均明显高于 NG 组织（TCGA 数据库 P<0.0001，临床样本 P=0.0034），免疫组化显示 13 例临床 GC 中有 9 例（69.23%）高表达 OLFML2B，且与肿瘤浸润深度和临床分期（TNM）呈正相关。此外，ROC 曲线的 AUC 为 0.867，表明 OLFML2B 对 GC 具有中等诊断能力。Kaplan-Meier plotter（P=2.6×10）和 OncoLnc（P=0.00276）的生存分析表明，OLFML2B 高表达与总生存期缩短相关。此外，从 cBioPortal 中鉴定出 OLFML2B 的 5%（24/478）改变，其中错义突变（14/478）是主要类型。FunRich 的结果表明，OLFML2B 通过 M/G1 转换途径、翻译后蛋白修饰和 DNA 复制起始前等多种信号通路，参与调节细胞生长和维持、细胞周期调控、细胞凋亡和细胞通讯等多种生物学过程。
综上所述，OLFML2B 可能在 GC 的发生发展中发挥癌基因作用，GC 中 OLFML2B 的过表达可作为 GC 的一种新型诊断和预后靶点。
