Yu Mengsi, Zhang Kainan, Wang Song
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Department of Clinical Laboratory, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
Heliyon. 2024 Jul 31;10(15):e35532. doi: 10.1016/j.heliyon.2024.e35532. eCollection 2024 Aug 15.
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.
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.
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.
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.
研究证实，鞘氨醇激酶1（SPHK1）/1-磷酸鞘氨醇受体（S1PRs）和血小板衍生生长因子受体（PDGFRs）在肿瘤的发生和发展中起重要作用。然而，SPHK1/S1PRs和PDGFRs在结肠腺癌（COAD）中的表达及临床价值仍不清楚。本研究旨在探讨SPHK1/S1PRs和PDGFRs在COAD中的表达，并进一步研究它们在预测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SPHK1/S1PRs和PDGFRs的表达。采用Kaplan-Meier生存分析评估SPHK1/S1PRs和PDGFRs在COAD患者中的预后作用。进行Spearman相关性分析以评估COAD中SPHK1/S1PRs与PDGFRs之间的关系。然后，进行χ2检验以分析SPHK1/S1PR3/PDGFRB与患者临床病理特征之间的相关性。此外，使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）功能富集分析预测S1PR3和PDGFRB共同调控的可能信号通路。使用最小绝对收缩和选择算子（LASSO）回归来识别共同调控S1PR3和PDGFRB表达的枢纽基因。为COPD患者构建基于枢纽基因的预后模型。最后，研究枢纽基因与肿瘤免疫细胞浸润之间的关系。
COAD患者组织中SPHK1和PDGFRB的表达水平显著上调（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）短于低表达患者（分别为P = 0.013和P = 0.005）。Spearman相关性分析证实S1PR3和PDGFRB的表达之间存在强正相关（P < 0.001，r = 0.790）。此外，我们发现SPHK1和PDGGRB高表达水平与神经周围浸润相关（分别为P < 0.001和P = 0.011）。S1PR3和PDGGRB的高表达与N分期显著相关（分别为P = 0.002和P = 0.021）。SPHK1、S1PR3和PDGFRB的高水平与淋巴结浸润相关（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细胞外基质组织和细胞信号转导。使用LASSO回归鉴定出五个枢纽基因，即SFRP2、GPRC5B、RSPO3、FGF14和TCF7L1。生存分析表明，高风险组的OS明显短于低风险组。结果表明，与低风险组相比，高风险组中的肿瘤免疫细胞显著增加。
S1PR3和PDGFRB可能是预测COAD患者淋巴转移和预后不良的重要标志物。潜在机制可能涉及免疫细胞浸润。
