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BRCA1 相互作用蛋白 C 端解旋酶 1(BRIP1)在人类肿瘤中的多分子特征和作用:泛癌分析。

Multimolecular characteristics and role of BRCA1 interacting protein C-terminal helicase 1 (BRIP1) in human tumors: a pan-cancer analysis.

机构信息

Department of Otolaryngology-Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong, 266000, China.

Qingdao Women and Children's Hospital, Qingdao University, Qingdao, Shandong, 266000, China.

出版信息

World J Surg Oncol. 2023 Mar 13;21(1):91. doi: 10.1186/s12957-022-02877-8.

Abstract

BACKGROUND

The aberrant expression of BRIP1 was associated with several cancers; however, the panoramic picture of BRIP1 in human tumors remains unclear. This study aims to explore the pan-cancerous picture of the expression of BRIP1 across 33 human cancers.

METHODS

Based on the data from TCGA and GTEx, a series of bioinformatic analyses were applied to systematically explore the genetic landscape and biologic function of BRIP1 in 33 human tumors.

RESULTS

We observed prognosis-related differential BRIP1 expressions between various carcinomas and the corresponding normal tissues. "Basal transcription factors," "homologous recombination," "nucleotide excision repair," and DNA metabolism pathways may play a role in the functional mechanisms of BRIP1. Patients with uterine corpus endometrial carcinoma presented with the highest alteration frequency of BRIP1 (nearly 10%). Single-nucleotide and copy number variations of BRIP1 were noticed in multiple cancers, and the expression of BRIP1 is significantly regulated by copy number variation in breast invasive carcinoma and lung squamous cell carcinoma. BRIP1 expression is negatively correlated with the DNA methylation levels in many tumors and is associated with the activation of apoptosis, cell cycle, DNA damage response, and inhibition of hormone ER and RNS/MARK signaling pathways. Moreover, a positive correlation was observed between BRIP1 expression and the immune infiltration levels of cancer-associated fibroblasts and CD8+ T cells in lung adenocarcinoma.

CONCLUSION

Our pan-cancer analysis of BRIP1 provides a valuable resource for understanding the multimolecular characteristics and biological function of BRIP1 across human cancers.

摘要

背景

BRIP1 的异常表达与多种癌症有关;然而,BRIP1 在人类肿瘤中的全景图仍不清楚。本研究旨在探讨 BRIP1 在 33 种人类肿瘤中的泛癌表达图谱。

方法

基于 TCGA 和 GTEx 的数据,应用一系列生物信息学分析方法系统地探讨了 BRIP1 在 33 种人类肿瘤中的遗传景观和生物学功能。

结果

我们观察到各种癌和相应正常组织之间与预后相关的 BRIP1 表达差异。“基础转录因子”、“同源重组”、“核苷酸切除修复”和 DNA 代谢途径可能在 BRIP1 的功能机制中发挥作用。子宫体子宫内膜癌患者的 BRIP1 改变频率最高(近 10%)。BRIP1 的单核苷酸和拷贝数变异在多种癌症中都有发现,并且在乳腺癌和肺鳞状细胞癌中,BRIP1 的表达受到拷贝数变异的显著调控。BRIP1 的表达与许多肿瘤中的 DNA 甲基化水平呈负相关,与细胞凋亡、细胞周期、DNA 损伤反应以及激素 ER 和 RNS/MARK 信号通路的抑制有关。此外,在肺腺癌中,BRIP1 表达与癌症相关成纤维细胞和 CD8+T 细胞的免疫浸润水平呈正相关。

结论

我们对 BRIP1 的泛癌分析为理解 BRIP1 在人类癌症中的多分子特征和生物学功能提供了有价值的资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaf3/10010046/f60d9d54b2d8/12957_2022_2877_Fig1_HTML.jpg

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