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PIK3CA作为肾透明细胞癌预后和免疫浸润相关标志物的鉴定与验证

Identification and Validation of PIK3CA as a Marker Associated with Prognosis and Immune Infiltration in Renal Clear Cell Carcinoma.

作者信息

Li Ya, Wang Chong, Gao Yang, Zhou Liang

机构信息

Department of Clinical Medicine, Dalian Medical University, Dalian 116044, China.

Department of Obstetrics and Gynecology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

J Oncol. 2021 Jul 27;2021:3632576. doi: 10.1155/2021/3632576. eCollection 2021.

Abstract

BACKGROUND

Kidney renal clear cell carcinoma (KIRC) is the most prevalent renal malignancy. The therapeutic strategies for advanced KIRC are very few, with only sunitinib being widely approved. Mutations in the PIK3CA gene can affect tumor cell proliferation, metastasis, and patients' survival.

METHODS

Bioinformatics analysis was performed to explore the expression and clinical significance of PIK3CA in KIRC. Moreover, qRT-PCR was conducted to verify the result.

RESULTS

Subgroup analyses of KIRC tissue based on gender, tumor grade, and cancer stage indicated downregulation of PIK3CA mRNA expression. The KIRC patients with high PIK3CA expression indicated a better overall survival, progression-free survival, and disease-free survival. A predictive nomogram was constructed and demonstrated that the calibration plots for the 3-year and 5-year OS rates were predicted relatively well compared with an ideal model in the TCGA KIRC cohort. The validation study revealed that downregulation of PIK3CA in KIRC tissues and low PIK3CA expression had a poor overall survival with an AUC of 0.775 in the ROC curve. Moreover, Cox regression analysis revealed that PIK3CA expression and clinical stage were independent factors affecting the prognosis of KIRC patients. PIK3CA expression was found to be significantly associated with the abundance of immune cells and immune biomarker sets. PIK3CA and associated genes were found to be mainly associated with immune response and the JAK-STAT signaling pathway.

CONCLUSION

We identified PIK3CA as a potential biomarker for prognosis correlated with immune infiltrates in KIRC. Further studies should focus on the functions of PIK3CA in KIRC carcinogenesis.

摘要

背景

肾透明细胞癌(KIRC)是最常见的肾脏恶性肿瘤。晚期KIRC的治疗策略非常有限,只有舒尼替尼被广泛批准。PIK3CA基因的突变可影响肿瘤细胞的增殖、转移及患者的生存。

方法

进行生物信息学分析以探究PIK3CA在KIRC中的表达及临床意义。此外,进行qRT-PCR以验证结果。

结果

基于性别、肿瘤分级和癌症分期对KIRC组织进行亚组分析,结果表明PIK3CA mRNA表达下调。PIK3CA高表达的KIRC患者总体生存期、无进展生存期和无病生存期更佳。构建了预测列线图,结果显示在TCGA KIRC队列中,与理想模型相比,3年和5年总生存率的校准图预测效果相对较好。验证研究表明,KIRC组织中PIK3CA下调和PIK3CA低表达的患者总体生存期较差,ROC曲线下面积为0.775。此外,Cox回归分析显示,PIK3CA表达和临床分期是影响KIRC患者预后的独立因素。发现PIK3CA表达与免疫细胞和免疫生物标志物集的丰度显著相关。PIK3CA及相关基因主要与免疫反应和JAK-STAT信号通路相关。

结论

我们将PIK3CA鉴定为与KIRC中免疫浸润相关的潜在预后生物标志物。进一步的研究应聚焦于PIK3CA在KIRC致癌过程中的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc24/8337125/d26a9e08a357/JO2021-3632576.001.jpg

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