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过表达的假基因MT1L与肿瘤免疫浸润相关,并提示膀胱癌预后较差。

Overexpressed pseudogene MT1L associated with tumor immune infiltrates and indicates a worse prognosis in BLCA.

作者信息

Ding Yanpeng, Liu Nuomin, Chen Mengge, Xu Yulian, Fang Sha, Xiang Wenbin, Hua Xinying, Chen Gaili, Zhong Yahua, Yu Haijun

机构信息

Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

Department of Oncology, First People's Hospital of Zaoyang, Zaoyang, 441200, China.

出版信息

World J Surg Oncol. 2021 Apr 22;19(1):133. doi: 10.1186/s12957-021-02231-4.

Abstract

BACKGROUND

BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined.

METHODS

Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function.

RESULTS

The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA.

CONCLUSION

Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.

摘要

背景

膀胱癌是全球常见的癌症,具有侵袭性且致命。免疫疗法(ICT)在膀胱癌中取得了优异的治疗效果;然而,只有部分膀胱癌患者能从ICT中获益。MT1L是一个假基因,先前的一项研究表明MT1L可作为结直肠癌预后的指标。然而,MT1L在膀胱癌中的作用尚未确定。

方法

从TCGA收集数据,进行逻辑回归、Kaplan-Meier绘图分析和多变量Cox分析,以证明假基因MT1L与膀胱癌预后之间的相关性。为确定MT1L与肿瘤浸润免疫细胞的关联,使用了TIMER和TISIDB。此外,进行基因集富集分析(GSEA)以阐明潜在的生物学功能。

结果

MT1L在膀胱癌中的表达降低。此外,MT1L与免疫细胞呈正相关,如调节性T细胞(ρ = 0.708)和骨髓来源的抑制性细胞(MDSCs,ρ = 0.664)。我们还证实MT1L与免疫细胞的典型标志物相关,如程序性死亡受体1(PD-1)和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)。此外,MT1L高表达水平与膀胱癌的晚期T和N分期以及高级别相关。MT1L表达增加与膀胱癌患者较短的总生存期显著相关(p < 0.05)。多变量Cox分析显示,MT1L表达可能是膀胱癌的独立预后因素。

结论

总体而言,我们的研究结果表明,假基因MT1L调节免疫微环境,与不良生存相关,是膀胱癌的独立预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4f6/8063461/ad942d03e990/12957_2021_2231_Fig1_HTML.jpg

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