SPP1 与不良预后相关，并可预测阴茎癌的免疫治疗疗效。
SPP1 is associated with adverse prognosis and predicts immunotherapy efficacy in penile cancer.
机构信息
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
State Key Laboratory of Oncology in Southern China, Guangzhou, 510060, China.
出版信息
Hum Genomics. 2023 Dec 19;17(1):116. doi: 10.1186/s40246-023-00558-5.
BACKGROUND
The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC.
METHOD
Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer.
RESULTS
Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer.
CONCLUSION
Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.
背景
SPP1 在阴茎鳞癌（PSCC）中的作用尚不清楚。我们试图阐明 SPP1 基因在 PSCC 中的功能。
方法
对 8 对阴茎癌标本（包括阴茎癌组织、癌旁组织和阳性淋巴结组织）进行全转录组测序分析，以鉴定差异表达基因。我们使用免疫组织化学检测 SPP1 蛋白和免疫细胞相关蛋白在阴茎癌组织中的表达。然后，我们进行加权基因共表达网络分析（WGCNA），以鉴定阴茎癌组织和阳性淋巴结组织中与 SPP1 相关的基因。基于 GSE57955 数据集，采用 CIBERSORT 和 ssGSEA 算法分析 PSCC 的免疫环境。GSVA 分析用于鉴定与 SPP1 亚组相关的信号通路。采用酶联免疫吸附试验（ELISA）法检测 60 例阴茎癌患者血清中 SPP1 水平。
结果
差异分析表明，SPP1 是阴茎癌组织和阳性淋巴结组织中差异上调最明显的基因。生存分析表明，低 SPP1 组的预后明显差于高 SPP1 组。随后，免疫相关的生物信息学显示，SPP1 与 B 细胞、CD8+T 细胞、CD4+T 细胞、巨噬细胞、辅助 T 细胞、中性粒细胞和树突状细胞显著相关。免疫组化结果显示，高 SPP1 组的 CD16 表达较高，CD4 表达较低。GSVA 分析表明，高 SPP1 组与 PD-L1 表达和癌症中的 PD-1 检查点通路以及 TNF 信号通路等免疫相关通路显著相关。ELISA 显示，阴茎癌阳性淋巴结转移患者的血清 SPP1 水平明显高于阴茎癌阴性淋巴结转移患者。
结论
本研究表明，SPP1 基因可能是预测 PSCC 患者预后和免疫治疗疗效的有效生物标志物。
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