整合多数据库分析NFKBIA在SKCM预后和免疫浸润中的价值

Analysis of the value of NFKBIA in prognosis and immune infiltration of SKCM based on multiple public databases

目的:探讨核因子κB抑制因子a(NFKBIA)表达与皮肤黑色素瘤(SKCM)患者预后及其与肿瘤微环境免疫浸润的相关性。方法:利用GEPIA2数据库分析正常皮肤和SKCM组织中NFKBIA的表达差异,GEPIA2和Ualcan数据库分析NFKBIA与SKCM预后关系,TIMER和TISIDB数据库分析NFKBIA与SKCM中TIL和免疫调节基因的关系。选用TISCH和CancerSEA数据库从单细胞水平分析NFKBIA与SKCM细胞亚群及其相关的功能状态关联性。选取湖北省荆门市第二人民医院保存的14例SKCM患者的石蜡组织标本,通过免疫组织化学染色法验证SKCM组织和癌旁组织中NFKBIA蛋白的表达水平。结果:NFKBIA在SKCM组织中呈低表达,并且低表达的SKCM患者预后差(P<0.05)。NFKBIA表达与B细胞、CD8+T细胞、CD4+T细胞、巨噬细胞、中性粒细胞和DC浸润水平呈正相关关系(均P<0.01)。NFKBIA表达与SKCM中TIL丰度和免疫调节基因呈正相关关系(均P<0.01)。NFKBIA在SKCM单细胞免疫细胞中表达,且与肿瘤微环境中细胞分化和炎症呈正相关关系(R=0.28、0.23,均P<0.05)。免疫组织化学染色结果证实,NFKBIA蛋白在SKCM组织中阳性表达率显著低于癌旁组织(35.71%vs 85.71%,P<0.05)。结论:NFKBIA在SKCM组织中呈低表达,与SKCM免疫细胞浸润相关,可作为SKCM预后的标志物及治疗靶点。

Objective:To evaluate the association between the expression of NF-kB inhibitor alpha(NFKBIA)gene and the prognosis and immune infiltration of the tumor microenvironment in patients with skin cutaneous melanoma(SKCM). Methods:GEPIA2database was used to analyze the differential expression of NFKBIA in SKCM tissues and normal skin tissues. GEPIA2 and Ualcan databases were utilized to analyze the association between NFKBIA expression and SKCM prognosis. TIMER and TISIDB were used to investigate the correlation between NFKBIA and tumor-infiltrating lymphocytes(TIL)and immune regulator genes in SKCM. The association between NFKBIA and subsets of SKCM cells as well as their functional states were analyzed at single-cell level in TISCH and Cancer SEA databases. The paraffin embedded tissues from 14 SKCM patients preserved in Jingmen No.2 People′s Hospital were obtained for this study, and immunohistochemical staining was used to detect the NFKBIA protein expression in SKCM tissues and para-cancerous tissues. Results:NFKBIA was lowly expressed in SKCM tissues, and SKCM patients with low NFKBIA expression had a poor prognosis(P<0.05). NFKBIA expression level was positively correlated with the infiltration of B cells, CD8+T cells, CD4+T cells, macrophages, neutrophils and dendritic cells(all P<0.01). What’s more, the expression of NFKBIA was positively correlated with TIL abundance and immunoregulatory genes(all P<0.01). NFKBIA was expressed in SKCM immune cells and positively correlated with cell differentiation and inflammation in tumor microenvironment(R=0.28, 0.23, all P<0.05). Immunohistochemical staining results demonstrated that the protein expression of NFKBIA was significantly lower in SKCM tissues than that in para-cancerous tissues(35.71% vs 85.71%, P<0.05). Conclusions:NFKBIA has a low expression in SKCM tissues, and it is correlated with immune infiltration in SKCM, which can be used as a prognostic marker and treatment target for SKCM.