CXCR4 is a Novel Biomarker Correlated With Malignant Transformation and Immune Infiltrates in Gastric Precancerous Lesions.
CXCR4 is a Novel Biomarker Correlated With Malignant Transformation and Immune Infiltrates in Gastric Precancerous Lesions.
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CXCR4是一种与胃癌前病变恶性转化和免疫浸润相关的新型生物标志物
DOI：
10.3389/fmolb.2021.697993
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发表时间：
2021
影响因子：
5
通讯作者：
Li P
中科院分区：
文献类型：
--
作者：
Jiang X;Zheng J;Liu L;Jiang K;Wen Y;Yan Y;Liu Y;Zhong L;Huang Y;Yao Z;Nie K;Zheng Z;Pan J;Liu P;Zhuang K;Liu F;Xu S;Li P
背景：由于早期胃癌（EGC）的预后远好于进展期胃癌（GC），因此早期诊断和治疗至关重要。然而，对胃癌前病变（GPL）发展为EGC的机制的研究进展甚微。此外，能够监测GPL向GC进展的生物标志物仍然非常不足。研究方法：通过使用WGCNA方法整合两个GPL相关数据集GSE 55696和GSE 130823，鉴定了与GPL进展为EGC相关的关键基因模块。结合TCGA-STAD队列，确定了枢纽基因。进行免疫荧光以验证表达。为探讨hub基因在GPL恶性转化中的意义，进行相关性检验，以鉴定hub基因共表达的基因、共表达的细胞因子和共表达的免疫细胞。应用最小绝对收缩和选择算子（LASSO）考克斯回归来收缩CXCR 4相关预测因子并构建预后模型。功能富集用于探索潜在的机制。结果如下：GSE 55696中的绿色模块和GSE 130823中的黄色模块被认为是与GPL向EGC进展相关的关键基因模块，其中219个交叉基因主要富集在关键免疫生物学过程中。结合TCGA-STAD队列，CXCR 4被确定为与GPL恶变相关的新生物标志物，根据免疫荧光，其阳性率随着GPL进展而增加。CXCR 4共表达基因主要参与肌动蛋白的调控。CXCR 4共表达细胞因子在调节趋化性、细胞趋化性、单核细胞迁移、白细胞趋化性等方面富集。在共表达免疫细胞中，CXCR 4表达水平与巨噬细胞丰度呈正相关，与效应记忆T细胞和NKT细胞呈负相关。此外，CXCR 4相关的预后模型能够预测GC的预后，并作为总生存期（OS）的独立预测因子。结论：CXCR 4是一种新的与GPL恶性转化相关的生物标志物，在肿瘤免疫调控中起重要作用。CXCR 4有可能成为GPL恶性转化的治疗靶点。
Background: As early gastric cancer (EGC) has a far better prognosis than advanced gastric cancer (GC), early diagnosis and treatment are essential. However, understanding the mechanism of the process from gastric precancerous lesion (GPL) becoming EGC has made little advances. Besides, biomarkers that can monitor the progression of GPL-to-GC are still much insufficient. Methods: Key gene modules associated with GPL progression to EGC were identified by integrating two GPL-related data sets, GSE55696 and GSE130823, using the WGCNA method. Combining with the TCGA-STAD cohort, hub genes were identified. Immunofluorescence was conducted to validate the expression. To explore the implication of hub genes in GPL malignant transformation, a correlation test was conducted to identify their co-expression genes, co-expression cytokines, and co-expression immune cells. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to shrink CXCR4-related predictors and construct a prognostic model. Functional enrichment was applied for exploring the potential mechanism. Results: The green module in GSE55696 and the yellow module in GSE130823 were regarded as key gene modules associated with GPL progression to EGC, and 219 intersection genes from them were mainly enriched in critical immune biological processes. Combining with the TCGA-STAD cohort, CXCR4 was identified as a novel biomarker correlated with the malignant transformation of GPL, the positive rate of which was increased with GPL progression according to immunofluorescence. CXCR4 co-expression genes were found mainly involved in regulation of actin. CXCR4 co-expression cytokines were enriched in regulation of chemotaxis, cell chemotaxis, mononuclear cell migration, leukocyte chemotaxis, etc. As for co-expression immune cells, the expression level of CXCR4 was positively correlated with the abundance of macrophages but negatively correlated with that of effector memory T cells and NKT cells during GPL malignant transformation. In addition, the CXCR4-related prognostic model was able to predict the prognosis of GC and serve as an independent predictor for overall survival (OS). Conclusions: CXCR4 was a novel biomarker correlated with malignant transformation of GPL and played a vital role in the control of tumor immunity. CXCR4 is possible to serve as a therapeutic target for malignant transformation of GPL.
影响因子：
3
作者：
Uloza V;Liutkevicius V;Pangonyte D;Lesauskaite V
通讯作者：
Lesauskaite V