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MRTO4 作为一个独立的预后和免疫生物标志物,与肝癌的肿瘤微环境相关。

MRTO4 acts as an independent prognostic and immunological biomarker and is correlated with tumor microenvironment in hepatocellular carcinoma.

机构信息

Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Department of Breast Surgery, Shaanxi Provincial Cancer Hospital, Xi'an, Shaanxi, China.

出版信息

Braz J Med Biol Res. 2024 Nov 4;57:e13780. doi: 10.1590/1414-431X2024e13780. eCollection 2024.

Abstract

Liver cancer is a malignant tumor found worldwide. mRNA turnover 4 homolog (MRTO4) is highly expressed in hepatocellular carcinoma (HCC) tissues, and we explored its relationship with HCC. All cancer data were downloaded from the Cancer Genome Atlas (TCGA), the Cancer Immune Atlas (TCIA), and the Human Protein Atlas (THPA). Stromal scores, immune scores, and ESTIMATE scores were calculated by "ESTIMATE" R package. Single sample gene set enrichment analysis and CIBERSORT were used to evaluate the immune status and infiltration of cancer tissues. pRRophetic R package was used to predict the half-maximal inhibitory concentration (IC50) of different drugs in each sample. MRTO4 overexpression was associated with poor prognosis in HCC, and positively correlated with the stage and grade of HCC patients. The average immunophenoscore (IPS) of the low MRTO4 group was significantly higher than that of the high MRTO4 group. Tumor microenvironment (TME) scores were significantly higher in the low MRTO4 group than in the high MRTO4 group in HCC. MRTO4 expression was positively correlated with tumor mutation burden (TMB) and was positively correlated with most immune checkpoint gene expressions in HCC. Drug sensitivity analysis showed significantly higher IC50 values for 5-fluorouracil, gemcitabine, and sorafenib in patients with low MRTO4 expression than in those with high MRTO4 expression. MRTO4 acts as an independent prognostic and immunological biomarker and is correlated with clinical stage, tumor grade, and drug sensitivity in HCC. It may serve as a putative therapeutic target and potential biomarker for prognosis of HCC.

摘要

肝癌是一种在全球范围内发现的恶性肿瘤。mRNA 周转率 4 同源物 (MRTO4) 在肝细胞癌 (HCC) 组织中高度表达,我们探讨了它与 HCC 的关系。所有癌症数据均从癌症基因组图谱 (TCGA)、癌症免疫图谱 (TCIA) 和人类蛋白质图谱 (THPA) 下载。基质评分、免疫评分和 ESTIMATE 评分通过 "ESTIMATE" R 包计算。单样本基因集富集分析和 CIBERSORT 用于评估癌症组织的免疫状态和浸润情况。pRRophetic R 包用于预测每个样本中不同药物的半最大抑制浓度 (IC50)。MRTO4 过表达与 HCC 的不良预后相关,并与 HCC 患者的分期和分级呈正相关。低 MRTO4 组的平均免疫表型评分 (IPS) 明显高于高 MRTO4 组。低 MRTO4 组的肿瘤微环境 (TME) 评分明显高于高 MRTO4 组。MRTO4 表达与肿瘤突变负担 (TMB) 呈正相关,与 HCC 中大多数免疫检查点基因表达呈正相关。药物敏感性分析显示,低 MRTO4 表达患者对 5-氟尿嘧啶、吉西他滨和索拉非尼的 IC50 值明显高于高 MRTO4 表达患者。MRTO4 作为独立的预后和免疫生物标志物,与 HCC 的临床分期、肿瘤分级和药物敏感性相关。它可能成为 HCC 预后的潜在治疗靶点和候选生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08df/11540254/44f558ef204e/1414-431X-bjmbr-57-e13780-gf001.jpg

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