Research Center of Clinical Laboratory Science, Bengbu Medical College, Bengbu, 233030, China.
Department of Genetics, School of Life Sciences, Bengbu Medical College, Bengbu, 233000, China.
Sci Rep. 2023 Apr 20;13(1):6459. doi: 10.1038/s41598-023-33404-8.
Lung adenocarcinoma is still cancer with the highest mortality. Hypoxia and immunity play an essential role in the occurrence and development of tumors. Therefore, this study is mainly to find new early diagnosis and prognosis markers and explore the relationship among the markers and immunity and hypoxia, to improve the prognosis of patients. Firstly, based on the clinical database in TCGA, we determined the most critical clinicopathological parameters affecting the prognosis of patients through a variety of analysis methods. According to pathological parameters, logistic most minor absolute contraction selection operator (lasso), univariate and multivariate regression analysis, the risk genes related to early prognosis were screened, and the risk model was established. Then, in different risk groups, GSEA and CIBERSORT algorithms were used to analyze the distribution and enrichment of the immune cells and hypoxia, to study the effects of early prognostic indicators on hypoxia and immunity. At the same time, we analyzed the different levels of risk genes in normal cells (BSEA-2B) and tumor cells (H1299, A549, PC9, and H1975). Finally, A549 and PC9 cells were induced by CoCl2 to establish a hypoxic environment, and the correlation between risk genes and HIF1A was analyzed. The risk model based on risk genes (CYP4B1, KRT6A, and FAM83A) was accurate and stable for the prognosis of patients. It is closely related to immunity and hypoxia. In BSEA-2B cells, the mRNA and protein expression of CYP4B1 was higher, while the expression of KRT6A and FAM83A was lower. Finally, we found that FAM83A and HIF1A showed a significant positive correlation when A549 and PC9 cells were exposed to hypoxia. The discovery of early diagnostic markers related to immunity, hypoxia, and prognosis, provides a new idea for early screening and prognostic treatment of lung adenocarcinoma.
肺腺癌仍然是死亡率最高的癌症。缺氧和免疫在肿瘤的发生和发展中起着至关重要的作用。因此,本研究主要是寻找新的早期诊断和预后标志物,并探讨这些标志物与免疫和缺氧之间的关系,以改善患者的预后。首先,基于 TCGA 的临床数据库,我们通过多种分析方法确定了影响患者预后的最关键的临床病理参数。根据病理参数,逻辑最小绝对收缩选择算子(lasso)、单变量和多变量回归分析筛选出与早期预后相关的风险基因,并建立风险模型。然后,在不同的风险组中,使用 GSEA 和 CIBERSORT 算法分析免疫细胞和缺氧的分布和富集情况,研究早期预后指标对缺氧和免疫的影响。同时,我们分析了正常细胞(BSEA-2B)和肿瘤细胞(H1299、A549、PC9 和 H1975)中不同风险基因的水平。最后,用 CoCl2 诱导 A549 和 PC9 细胞建立缺氧环境,分析风险基因与 HIF1A 的相关性。基于风险基因(CYP4B1、KRT6A 和 FAM83A)的风险模型对患者的预后准确且稳定,与免疫和缺氧密切相关。在 BSEA-2B 细胞中,CYP4B1 的 mRNA 和蛋白表达较高,而 KRT6A 和 FAM83A 的表达较低。最后,我们发现当 A549 和 PC9 细胞暴露于缺氧时,FAM83A 和 HIF1A 表现出显著的正相关。发现与免疫、缺氧和预后相关的早期诊断标志物,为肺腺癌的早期筛查和预后治疗提供了新的思路。