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全面描绘卵巢癌中的可变剪接图谱揭示了与肿瘤免疫微环境相关的新事件。

Comprehensive characterization of the alternative splicing landscape in ovarian cancer reveals novel events associated with tumor-immune microenvironment.

机构信息

Department of Gynecology, Third Xiangya Hospital of Central South University, Changsha 410013, Hunan, China.

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China.

出版信息

Biosci Rep. 2022 Feb 25;42(2). doi: 10.1042/BSR20212090.

DOI:10.1042/BSR20212090
PMID:35137909
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8829021/
Abstract

BACKGROUND

Ovarian cancer (OV) is a serious threat to women's health. Immunotherapy is a new approach. Alternative splicing (AS) of messenger RNA (mRNA) and its regulation are highly relevant for understanding every cancer hallmark and may offer a broadened target space.

METHODS

We downloaded the clinical information and mRNA expression profiles of 587 tumor tissues from The Cancer Genome Atlas (TCGA) database. We constructed a risk score model to predict the prognosis of OV patients. The association between AS-based clusters and tumor-immune microenvironment features was further explored. The ESTIMATE algorithm was also carried out on each OV sample depending on the risk score groups. A total of three immune checkpoint genes that have a significant correlation with risk scores were screened.

RESULTS

The AS-events were a reliable and stable independent risk predictor in the OV cohort. Patients in the high-risk score group had a poor prognosis (P<0.001). Mast cells activated, NK cells resting, and Neutrophils positively correlated with the risk score. The number of Macrophages M1 was also more numerous in the low-risk score group (P<0.05). Checkpoint genes CD274, CTLA-4, and PDCD1LG2, showed a negative correlation with the risk score of AS in OV.

CONCLUSIONS

The proposed AS signature is a promising biomarker for estimating overall survival (OS) in OV. The AS-events signature combined with tumor-immune microenvironment enabled a deeper understanding of the immune status of OV patients, and also provided new insights for exploring novel prognostic predictors and precise therapy methods.

摘要

背景

卵巢癌（OV）严重威胁着女性健康。免疫疗法是一种新方法。信使 RNA（mRNA）的选择性剪接（AS）及其调控与理解每种癌症标志密切相关，可能提供更广泛的靶向空间。

方法

我们从癌症基因组图谱（TCGA）数据库下载了 587 个肿瘤组织的临床信息和 mRNA 表达谱。我们构建了一个风险评分模型来预测 OV 患者的预后。进一步探讨了基于 AS 的聚类与肿瘤免疫微环境特征之间的关联。还根据风险评分组对每个 OV 样本进行了 ESTIMATE 算法分析。总共筛选出与风险评分显著相关的三个免疫检查点基因。

结果

AS 事件是 OV 队列中可靠且稳定的独立风险预测因子。高风险评分组患者预后不良（P<0.001）。肥大细胞激活、NK 细胞静止和中性粒细胞与风险评分呈正相关。低风险评分组中巨噬细胞 M1 的数量也更多（P<0.05）。在 OV 中，CD274、CTLA-4 和 PDCD1LG2 等检查点基因与 AS 的风险评分呈负相关。

结论

提出的 AS 特征是估计 OV 总生存期（OS）的有前途的生物标志物。AS 事件特征与肿瘤免疫微环境相结合，使我们能够更深入地了解 OV 患者的免疫状态，并为探索新的预后预测因子和精确治疗方法提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/77d5cb4f9298/bsr-42-bsr20212090-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/a29ec45fae97/bsr-42-bsr20212090-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/026a14511f70/bsr-42-bsr20212090-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/12abeb524dab/bsr-42-bsr20212090-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/3d8235db4013/bsr-42-bsr20212090-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/e33dc17a0656/bsr-42-bsr20212090-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/77d5cb4f9298/bsr-42-bsr20212090-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/a29ec45fae97/bsr-42-bsr20212090-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/026a14511f70/bsr-42-bsr20212090-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/12abeb524dab/bsr-42-bsr20212090-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/3d8235db4013/bsr-42-bsr20212090-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/e33dc17a0656/bsr-42-bsr20212090-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6d0/8829021/77d5cb4f9298/bsr-42-bsr20212090-g6.jpg

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