PIK3CD与乳腺癌的预后、上皮-间质转化及肿瘤免疫浸润相关。

PIK3CD correlates with prognosis, epithelial-mesenchymal transition and tumor immune infiltration in breast carcinoma.

作者信息

He Wenxing, Zhang Haoyi, Cheng Hong, Wen Jianfeng, Li Dongmei

机构信息

Breast Cancer Center, Jiangxi Cancer Hospital of Nanchang Medical College, No. 519 East Beijing Road, Nanchang, 330029, People's Republic of China.

School of Public Health, Nanchang University, Nanchang, 330006, China.

出版信息

Discov Oncol. 2023 Oct 20;14(1):187. doi: 10.1007/s12672-023-00805-0.

BACKGROUND

Breast carcinoma (BRCA) is one of the most common, fatal, and aggressive cancers, with increasing morbidity that has a major impact on human health. PIK3CD appears to have important roles in the beginning and advancement of various forms of human cancer, according to mounting data. However,the particular role and mechanism of PIK3CD in BRCA remains not fully identified.

METHODOLOGY

The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/ ), Genotype-Tissue Expression (GTEx) data and the UCSC Xena browser ( https://xenabrowser.net ) data were used in this study's initial pan-cancer analysis of PIK3CD expression and prognosis. Circular RNAs (circRNAs) that regulated the expression of PIK3CD were subsequently found using a combination of in silico investigations of expression, correlation, and survival. Measurements of PIK3CD expression and an analysis of the in vitro function of PIK3CD in BRCA cells were performed using real-time RT-PCR, Western blotting and Transwell assays.

RESULTS

In BRCA GLI2, RAB32, LAMB1, MGAT2, ITGA8, CHF, COL6A3 and PRRX1-miR-30b-5p axis was identified as the most likely upstream CircRNA-related route of PIK3CD. PIK3CD was correlated with the expression of EMT markers. The PIK3CD cDNA improved the capacity for invasion and migration. The expression of PIK3CD was linked to some of the m1A/m5C/m6A regulators. Additionally, it was discovered that the expression of PIK3CD was found to be highly connected to the expression of immunological checkpoints, immune cell biomarkers, and tumor immune cell invasion.

CONCLUSIONS

Our findings reveal that PIK3CD expression is associated with prognosis, EMT, and tumor immune infiltration in BRCA patients.

背景

乳腺癌（BRCA）是最常见、致命且侵袭性强的癌症之一，其发病率不断上升，对人类健康产生重大影响。越来越多的数据表明，PIK3CD在各种人类癌症的发生和发展中似乎发挥着重要作用。然而，PIK3CD在BRCA中的具体作用和机制仍未完全明确。

方法

本研究最初对PIK3CD的表达和预后进行泛癌分析时，使用了癌症基因组图谱（TCGA，https://portal.gdc.cancer.gov/）、基因型-组织表达（GTEx）数据以及加州大学圣克鲁兹分校Xena浏览器（https://xenabrowser.net）的数据。随后，通过对表达、相关性和生存的计算机模拟研究相结合，发现了调控PIK3CD表达的环状RNA（circRNA）。使用实时RT-PCR、蛋白质免疫印迹法和Transwell实验对BRCA细胞中PIK3CD的表达进行测量，并分析其体外功能。

结果

在BRCA中，GLI2、RAB32、LAMB1、MGAT2、ITGA8、CHF、COL6A3和PRRX1-miR-30b-5p轴被确定为PIK3CD最可能的上游circRNA相关途径。PIK3CD与上皮-间质转化（EMT）标志物的表达相关。PIK3CD cDNA提高了侵袭和迁移能力。PIK3CD的表达与一些m1A/m5C/m6A调节因子有关。此外，还发现PIK3CD的表达与免疫检查点、免疫细胞生物标志物的表达以及肿瘤免疫细胞浸润高度相关。