■研究证实,鞘氨醇激酶1(SPHK1)/鞘氨醇1-磷酸受体(S1PRs)和血小板衍生生长因子受体(PDGFR)在肿瘤的发生和发展中起重要作用。然而,SPHK1/S1PRs和PDGFR在结肠腺癌(COAD)中的表达和临床价值尚不清楚.本研究旨在探讨SPHK1/S1PRs和PDGFRs在COAD中的表达,并进一步探讨其在预测COAD患者预后中的作用。
使用癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库分析COAD患者组织中的SPHK1/S1PRs和PDGFR表达。Kaplan-Meier生存分析用于评估SPHK1/S1PRs和PDGFRs在COAD患者中的预后作用。采用Spearman相关分析评价COAD中SPHK1/S1PRs与PDGFRs的关系。然后,采用χ2检验分析SPHK1/S1PR3/PDGFRB与患者临床病理特征的相关性。此外,使用基因本体论(GO)和京都基因和基因组百科全书(KEGG)功能富集分析预测了S1PR3和PDGFRB共同调节的可能信号通路。使用最小绝对收缩和选择算子(LASSO)回归来鉴定共调节S1PR3和PDGFRB表达的hub基因。构建了基于hub基因的COPD患者预后模型。最后,研究了hub基因与肿瘤免疫细胞浸润的关系。
■COAD患者组织中SPHK1和PDGFRB的表达水平显着上调(分别为P<0.001和P<0.001)。此外,Kaplan-Meier分析显示,SPHK1和S1PR3高表达的COAD患者的总生存期(OS)短于低表达水平的COAD患者(P=0.013和P=0.005)。Spearman相关分析证实,S1PR3与PDGFRB的表达呈显著正相关(P<0.001,r=0.790)。此外,我们发现高SPHK1和PDGGRB表达水平与神经周侵袭相关(分别为P<0.001和P=0.011)。S1PR3和PDGGRB的高表达与N期显著相关(分别为P=0.002和P=0.021)。高水平的SPHK1、S1PR3和PDGFRB与淋巴结浸润相关。(分别为P=0.018,P=0.004和P=0.001)。GO和KEGG结果显示S1PR3和PDGFRB可能参与COAD细胞细胞外基质组织和细胞信号转导。五个枢纽基因,SFRP2,GPRC5B,使用LASSO回归鉴定RSPO3、FGF14和TCF7L1。生存分析显示,高危组的OS明显短于低危组。结果表明,与低危组相比,高危组的肿瘤免疫细胞显着增加。
■S1PR3和PDGFRB可能是预测COAD患者淋巴转移和不良预后的重要标志物。潜在的机制可能涉及免疫细胞浸润。
UNASSIGNED: Studies verified that sphingosine kinase 1 (SPHK1)/sphingosine 1-phosphate receptors (S1PRs) and platelet-derived growth factor receptors (PDGFRs) play important roles in tumor occurrence and progression. However, the expression and clinical value of SPHK1/S1PRs and PDGFRs in colon adenocarcinoma (COAD) remains unclear. This study aimed to explore the expression of SPHK1/S1PRs and PDGFRs in COAD and further investigate their roles in predicting the prognosis of patients with COAD.
UNASSIGNED: SPHK1/S1PRs and PDGFRs expression in tissues from patient with COAD were analyzed using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Kaplan-Meier survival analysis was used to evaluate the prognostic roles of SPHK1/S1PRs and PDGFRs in patients with COAD. Spearman\'s correlation analysis was performed to assess the relationship between SPHK1/S1PRs and PDGFRs in COAD. Then, χ2 test was performed to analyze the correlation between SPHK1/S1PR3/PDGFRB and clinicopathological characteristics of the patients. Additionally, possible signaling pathways co-regulated by S1PR3 and PDGFRB were predicted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Least absolute shrinkage and selection operator (LASSO) regression was used to identify hub genes that co-regulated S1PR3 and PDGFRB expression. A prognostic model based on hub genes was constructed for patients with COPD. Finally, the relationship between the hub genes and tumor immune cell infiltration was investigated.
UNASSIGNED: The expression levels of SPHK1 and PDGFRB were significantly upregulated in COAD patient tissues (P < 0.001 and P < 0.001, respectively). Moreover, Kaplan-Meier analysis showed that patients with COAD with high expression levels of SPHK1 and S1PR3 had shorter overall survival (OS) than those with low expression levels (P = 0.013 and P = 0.005, respectively). Spearman\'s correlation analysis verified a strong positive correlation (P < 0.001, r = 0.790) between the expression of S1PR3 and PDGFRB. In addition, we found that high SPHK1 and PDGGRB expression levels were associated with perineural invasion (P < 0.001 and P = 0.011, respectively). High expression of S1PR3 and PDGGRB was prominently associated with N stage (P = 0.002 and P = 0.021, respectively). High levels of SPHK1, S1PR3, and PDGFRB were associated with lymph node invasion. (P = 0.018, P = 0.004, and P = 0.001, respectively). GO and KEGG results revealed that S1PR3 and PDGFRB may participate in COAD cell extracellular matrix organization and cellular signal transduction. Five hub genes, SFRP2, GPRC5B, RSPO3, FGF14, and TCF7L1, were identified using LASSO regression. Survival analysis showed that the OS in the high-risk group was remarkably shorter than that in the low-risk group. The results indicated that tumor immune cells were significantly increased in the high-risk group compared to those in the low-risk group.
UNASSIGNED: S1PR3 and PDGFRB may be important markers for predicting lymphatic metastasis and poor prognosis in patients with COAD. The underlying mechanisms may involve immune cell infiltration.