肝细胞癌患者长链非编码 RNA LINC01116 及其相关蛋白编码基因的候选特征综合分析。
Comprehensive analysis of candidate signatures of long non-coding RNA LINC01116 and related protein-coding genes in patients with hepatocellular carcinoma.
机构信息
Departments of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Henan Province, Zhengzhou, 450052, P. R. China.
出版信息
BMC Gastroenterol. 2023 Jun 20;23(1):216. doi: 10.1186/s12876-023-02827-y.
BACKGROUND
Hepatocellular carcinoma (HCC) is a long-term malignancy that causes high morbidities and mortalities worldwide. Notably, long non-coding RNAs (LncRNAs) have been identified as candidate targets for malignancy treatments.
METHODS
LncRNA LINC01116 and its Pearson-correlated genes (PCGs) were identified and analyzed in HCC patients. The diagnostic and prognostic value of the lncRNA was evaluated using data from The Cancer Genome Atlas (TCGA). Further, we explored the target drugs of LINC01116 for clinical application. Relationships between immune infiltration and PCGs, methylation and PCGs were explored. The diagnostic potentials were then validated by Oncomine cohorts.
RESULTS
LINC01116 and the PCG OLFML2B are differentially and highly expressed in tumor tissues (both P ≤ 0.050). We found that LINC01116, TMSB15A, PLAU, OLFML2B, and MRC2 have diagnostic potentials (all AUC ≥ 0.700, all P ≤ 0.050) while LINC01116 and TMSB15A have prognostic significance (both adjusted P ≤ 0.050). LINC01116 was enriched in the vascular endothelial growth factor (VEGF) receptor signaling pathway, mesenchyme morphogenesis, etc. After that, candidate target drugs with potential clinical significance were identified: Thiamine, Cromolyn, Rilmenidine, Chlorhexidine, Sulindac_sulfone, Chloropyrazine, and Meprylcaine. Analysis of immune infiltration revealed that MRC2, OLFML2B, PLAU, and TMSB15A are negatively associated with the purity but positively associated with the specific cell types (all P < 0.050). Analysis of promoter methylation demonstrated that MRC2, OLFML2B, and PLAU have differential and high methylation levels in primary tumors (all P < 0.050). Validation results of the differential expressions and diagnostic potential of OLFML2B (Oncomine) were consistent with those obtained in the TCGA cohort (P < 0.050, AUC > 0.700).
CONCLUSIONS
Differentially expressed LINC01116 could be a candidate diagnostic and an independent prognostic signature in HCC. Besides, its target drugs may work for HCC therapy via the VEGF receptor signaling pathway. Differentially expressed OLFML2B could be a diagnostic signature involved in HCC via immune infiltrates.
背景
肝细胞癌（HCC）是一种长期存在的恶性肿瘤，在全球范围内导致高发病率和死亡率。值得注意的是，长链非编码 RNA（LncRNA）已被确定为恶性肿瘤治疗的候选靶点。
方法
在 HCC 患者中鉴定并分析 LncRNA LINC01116 及其 Pearson 相关基因（PCG）。使用来自癌症基因组图谱（TCGA）的数据评估 LncRNA 的诊断和预后价值。此外，我们还探索了 LINC01116 的靶向药物在临床应用中的应用。探讨了免疫浸润与 PCG、甲基化与 PCG 的关系。然后通过 Oncomine 队列验证诊断潜力。
结果
LINC01116 和 PCG OLFML2B 在肿瘤组织中差异表达且高度表达（均 P≤0.050）。我们发现 LINC01116、TMSB15A、PLAU、OLFML2B 和 MRC2 具有诊断潜力（均 AUC≥0.700，均 P≤0.050），而 LINC01116 和 TMSB15A 具有预后意义（均调整 P≤0.050）。LINC01116 在血管内皮生长因子（VEGF）受体信号通路、间质形态发生等方面富集。之后，确定了具有潜在临床意义的候选靶向药物：硫胺素、色甘酸钠、利美尼定、氯己定、舒林酸磺酰胺、氯吡嗪、美普卡因。免疫浸润分析表明，MRC2、OLFML2B、PLAU 和 TMSB15A 与纯度呈负相关，但与特定细胞类型呈正相关（均 P<0.050）。启动子甲基化分析表明，MRC2、OLFML2B 和 PLAU 在原发性肿瘤中具有差异高甲基化水平（均 P<0.050）。OLFML2B 的差异表达和诊断潜力的验证结果（Oncomine）与 TCGA 队列的结果一致（P<0.050，AUC>0.700）。
结论
差异表达的 LINC01116 可能是 HCC 的候选诊断和独立预后标志物。此外，其靶向药物可能通过 VEGF 受体信号通路对 HCC 治疗有效。差异表达的 OLFML2B 可能通过免疫浸润参与 HCC 的诊断。
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