Hu Pengbo, Zhang Xiuyuan, Li Yiming, Xu Liang, Qiu Hong
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Genet. 2022 Jul 6;13:882794. doi: 10.3389/fgene.2022.882794. eCollection 2022.
The function of olfactomedin-like 2B (OLFML2B), as a member of the olfactomedin domain-containing protein family, remains ambiguous, especially in tumors. The current study explores the possible correlation between OLFML2B, prognosis, and immune infiltration in pan-cancer. We applied a number of bioinformatics techniques to probe the prospective function of OLFML2B, consisting of its association with prognosis, clinicopathology, alteration, GSEA, tumor microenvironment (TME), immune-associated genes, immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and drug sensitivity in several cancer types. qPCR and immunohistochemistry were used to identify OLFML2B expression in LIHC cell lines and liver cancer tissues. We discovered that OLFML2B was overexpressed in 14 cancers and positively related to several cancer type prognoses. The expression of OLFML2B was further validated in the LIHC cell lines. OLFML2B expression was bound up with TMB in 13 cancers, MSI in 10 cancers, and TME in almost all cancers. Furthermore, OLFML2B was highly co-expressed with genes encoding immune activators and immune suppressors. We further found that OLFML2B played a role in infiltrating different types of immune cells, such as macrophages and cancer-associated fibroblasts. OLFML2B may influence various cancer and immune-related pathways, such as the PI3K-Akt signaling pathway, ECM-receptor interaction, focal adhesion, and leukocyte transendothelial migration. In addition, OLFML2B may increase drug resistance of binimetinib, cobimentinib, and trametinib. Our outcomes reveal that OLFML2B may act as a prognostic marker and a potential target in immunotherapy for diverse tumors due to its oncogenesis function and immune infiltration.
嗅觉介质样2B（OLFML2B）作为含嗅觉介质结构域蛋白家族的一员，其功能仍不明确，尤其是在肿瘤方面。当前研究探讨了泛癌中OLFML2B、预后和免疫浸润之间的可能关联。我们应用了多种生物信息学技术来探究OLFML2B的潜在功能，包括其与预后、临床病理、改变、基因集富集分析（GSEA）、肿瘤微环境（TME）、免疫相关基因、免疫浸润、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）以及几种癌症类型中药物敏感性的关联。采用定量聚合酶链反应（qPCR）和免疫组织化学方法来鉴定OLFML2B在肝癌细胞系和肝癌组织中的表达。我们发现OLFML2B在14种癌症中过表达，且与几种癌症类型的预后呈正相关。OLFML2B的表达在肝癌细胞系中得到了进一步验证。OLFML2B的表达在13种癌症中与TMB相关，在10种癌症中与MSI相关，并且在几乎所有癌症中都与TME相关。此外，OLFML2B与编码免疫激活剂和免疫抑制剂的基因高度共表达。我们进一步发现OLFML2B在不同类型免疫细胞（如巨噬细胞和癌症相关成纤维细胞）的浸润中发挥作用。OLFML2B可能影响各种癌症和免疫相关途径，如PI3K - Akt信号通路、细胞外基质 - 受体相互作用、粘着斑和白细胞跨内皮迁移。此外，OLFML2B可能增加比美替尼、考比替尼和曲美替尼的耐药性。我们的结果表明，由于其致癌作用和免疫浸润，OLFML2B可能作为多种肿瘤免疫治疗的预后标志物和潜在靶点。
