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利用TCGA数据库对头颈部鳞状细胞癌微环境中的预后生物标志物进行探索。

Exploration of prognostic biomarkers in head and neck squamous cell carcinoma microenvironment from TCGA database.

作者信息

Li Ying, Bi Jianping, Pi Guoliang, He Hanping, Li Yanping, Han Guang

机构信息

Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Ann Transl Med. 2023 Feb 28;11(4):163. doi: 10.21037/atm-22-6481.

Abstract

BACKGROUND

Immune checkpoint blockade (ICB) therapies have redefined human cancer treatment, including for head and neck squamous cell carcinoma (HNSCC). However, clinical responses to various immune checkpoint inhibitors are often accompanied by immune-related adverse events (irAEs). Therefore, it is crucial to obtain a comprehensive understanding of the association between different immune tumor microenvironments (TMEs) and the immunotherapeutic response.

METHODS

The research data were obtained from The Cancer Genome Atlas (TCGA) database. We applied RNA-seq genomic data from tumor biopsies to assess the immune TME in HNSCC. As the TME is a heterogeneous system that is highly associated with HNSCC progression and clinical outcome, we relied on the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm to calculate immune and stromal scores that were evaluated based on the immune or stromal components in the TME. Then, the Tumor Immune Dysfunction and Exclusion algorithm (TIDE) was used to predict the benefits of ICB to each patient. Finally, we identified specific prognostic tumor-infiltrating immune cells (TIICs) by quantifying the cellular composition of the immune response in HNSCC and its association to survival outcome, using the CIBERSORT algorithm.

RESULTS

Utilizing the HNSCC cohort of the TCGA database and TIDE and ESTIMATE algorithm-derived immune scores, we obtained a list of microenvironment-associated lncRNAs that predicted different clinical outcomes in HNSCC patients. We validated these correlations in a different HNSCC cohort available from the TCGA database and provided insight into the prediction of response to ICB therapies in HNSCC.

CONCLUSIONS

This study confirmed that CD8 T cells were significantly associated with better survival in HNSCC and verified that the top five significantly mutated genes (SMGs) in the TCGA HNSCC cohort were and A high level of CD8 T cells and high immune and stroma scores corresponded to a better survival probability in HNSCC.

摘要

背景

免疫检查点阻断(ICB)疗法重新定义了人类癌症治疗,包括对头颈部鳞状细胞癌(HNSCC)的治疗。然而,对各种免疫检查点抑制剂的临床反应常伴有免疫相关不良事件(irAE)。因此,全面了解不同免疫肿瘤微环境(TME)与免疫治疗反应之间的关联至关重要。

方法

研究数据来自癌症基因组图谱(TCGA)数据库。我们应用肿瘤活检的RNA测序基因组数据来评估HNSCC中的免疫TME。由于TME是一个与HNSCC进展和临床结果高度相关的异质系统,我们依靠使用表达数据估计恶性肿瘤组织中的基质和免疫细胞(ESTIMATE)算法来计算基于TME中免疫或基质成分评估的免疫和基质评分。然后,使用肿瘤免疫功能障碍和排除算法(TIDE)来预测ICB对每位患者的益处。最后,我们通过使用CIBERSORT算法量化HNSCC中免疫反应的细胞组成及其与生存结果之间的关联,确定了特定的预后肿瘤浸润免疫细胞(TIIC)。

结果

利用TCGA数据库的HNSCC队列以及TIDE和ESTIMATE算法得出的免疫评分,我们获得了一份与微环境相关的lncRNA列表,这些lncRNA可预测HNSCC患者的不同临床结果。我们在TCGA数据库中另一个可用的HNSCC队列中验证了这些相关性,并深入了解了HNSCC中对ICB疗法反应的预测。

结论

本研究证实CD8 T细胞与HNSCC更好的生存率显著相关,并验证了TCGA HNSCC队列中前五个显著突变基因(SMG)是 和 。HNSCC中高水平的CD8 T细胞以及高免疫和基质评分对应着更好的生存概率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43e2/10009575/a49bb24b1367/atm-11-04-163-f1.jpg

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