长链非编码RNA MIR22HG表达模式的泛癌分析
[Pan-cancer analysis of the expression pattern of long non-coding RNA MIR22HG].
作者信息
Wang H, Li W, Zhang D
机构信息
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2022 Apr 20;42(4):473-485. doi: 10.12122/j.issn.1673-4254.2022.04.03.
OBJECTIVE
To conduct a pan-cancer analysis of the expression of long non-coding RNA (lncRNA) MIR22HG and explore its association with clinical characteristics.
METHODS
We analyzed the expression of MIR22HG in different tumors and its association with clinical staging, lymph node metastasis, tumor mutation burden (TMB) and microsatellite instability (MSI) using R package based on the Cancer Genome Atlas (TCGA) datasets. The relationship between MIR22HG expression and infiltrating immune cells was analyzed using TIMER algorithm. The association of MIR22HG gene alteration frequency with the clinical outcomes was examined using cBioPortal online software. Data form Genomics of Drug Sensitivity in Cancer (GDSC) were used to analyze the relationship between MIR22HG and the sensitivity of chemotherapy drugs. We specifically analyzed MIR22HG expression in hepatocellular carcinoma (HCC) and its correlation with sorafenib treatment using GEO database and verified the results in 12 pairs of HCC specimens. Kaplan-Meier analysis was performed to analyze the correlation of MIR22HG with the outcomes of sorafenib treatment. We also tested the effects of MIR22HG overexpression and knockdown on IC of sorafenib in HCC cells.
RESULTS
MIR22HG was downregulated in most tumors ( < 0.05), where its deletion mutations were frequent, and associated with a poor prognosis ( < 0.05). In many tumors, MIR22HG expression level was correlated with clinical stage, lymph node metastasis, TMB, MSI, immune cell infiltration, immune checkpoint-related genes, and sensitivity to common chemotherapeutic drugs ( < 0.05). Among the 6 common infiltrating immune cells in cancers, neutrophil infiltration had the strongest correlation with MIR22HG expression level, especially in breast cancer, rectal cancer and kidney renal papillary cell carcinoma ( < 0.05). MIR22HG was downregulated in HCC in association with HCC progression ( < 0.05). In HCC patients, a low MIR22HG expression was associated with a favorable outcome after sorafenib treatment (HR=2.94, =0.075) and was capable of predicting the response to sorafenib treatment (AUC=0.8095). Compared with the negative control, MIR22HG overexpression obviously reduced sorafenib sensitivity (with IC of 7.731 15.61) while MIR22HG knockdown increased sorafenib sensitivity of HCC cells (with IC of 7.986 5.085).
CONCLUSION
MIR22HG expression level is correlated with clinical stage, lymph node metastasis, TMB, MSI, immune cell infiltration, and chemosensitivity in most cancer, suggesting its potential as an immunotherapeutic target and also a prognostic biomarker for tumors.
目的
对长链非编码RNA（lncRNA）MIR22HG的表达进行泛癌分析，并探讨其与临床特征的关联。
方法
我们基于癌症基因组图谱（TCGA）数据集，使用R包分析了MIR22HG在不同肿瘤中的表达及其与临床分期、淋巴结转移、肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）的关联。使用TIMER算法分析MIR22HG表达与浸润性免疫细胞之间的关系。使用cBioPortal在线软件检查MIR22HG基因改变频率与临床结局的关联。利用癌症药物敏感性基因组学（GDSC）的数据来分析MIR22HG与化疗药物敏感性之间的关系。我们使用GEO数据库专门分析了肝细胞癌（HCC）中MIR22HG的表达及其与索拉非尼治疗的相关性，并在12对HCC标本中验证了结果。进行Kaplan-Meier分析以分析MIR22HG与索拉非尼治疗结局的相关性。我们还测试了MIR22HG过表达和敲低对HCC细胞中索拉非尼半数抑制浓度（IC）的影响。
结果
MIR22HG在大多数肿瘤中表达下调（<0.05），其缺失突变频繁，且与预后不良相关（<0.05）。在许多肿瘤中，MIR22HG表达水平与临床分期、淋巴结转移、TMB、MSI、免疫细胞浸润、免疫检查点相关基因以及对常用化疗药物的敏感性相关（<0.05）。在癌症中6种常见的浸润性免疫细胞中，中性粒细胞浸润与MIR22HG表达水平的相关性最强，尤其是在乳腺癌、直肠癌和肾肾乳头状细胞癌中（<0.05）。MIR22HG在HCC中表达下调，与HCC进展相关（<0.05）。在HCC患者中，低MIR22HG表达与索拉非尼治疗后的良好结局相关（HR=2.94，=0.075），并且能够预测对索拉非尼治疗的反应（AUC=0.8095）。与阴性对照相比，MIR22HG过表达明显降低了索拉非尼敏感性（IC为7.731±15.61），而MIR22HG敲低增加了HCC细胞对索拉非尼的敏感性（IC为7.986±5.085）。
结论
MIR22HG表达水平与大多数癌症的临床分期、淋巴结转移、TMB、MSI、免疫细胞浸润和化疗敏感性相关，表明其作为免疫治疗靶点以及肿瘤预后生物标志物具有潜力。
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