Data Sheet 1_Deregulated methylation and expression of PCDHGB7 in patients with non-small cell lung cancer: a novel prognostic and immunological biomarker.pdf

BackgroundsProtocadherin gamma subfamily B, 7 (PCDHGB7), a member of the protocadherin family, plays critical roles in neuronal connections and has been implicated in female reproductive system cancers. Its function in lung cancer has not been elucidated.
MethodsWe comprehensively investigated PCDHGB7 expression, prognosis, biological function, methylation patterns, and it’s relationship with immune infiltration and immunotherapy response through public datasets (HPA, TCGA, GEO, OncoDB and MEXPRESS). Two lung cancer immunotherapy cohorts from our clinical center were enrolled to detect the relationship between methylation and protein levels of PCDHGB7 in plasma and immunotherapy outcomes.
ResultsPCDHGB7 expression was downregulated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and associated with tumor prognosis. PCDHGB7 demonstrated a positive correlation with inhibitory immune cells and a negative correlation with tumor mutational burden (TMB) and homologous recombination deficiency (HRD). The methylation level of PCDHGB7 was upregulated in tumor tissue and negatively correlated with PCDHGB7 mRNA level. In immunotherapy cohort studies, patients with higher PCDHGB7 tissue expression showed worse prognosis. Patients with PCDHGB7 hypermethylation in baseline plasma had shorter progression-free survival (PFS) and overall survival (OS), while those with early reduction of PCDHGB7 methylation had the best prognosis. Plasma PCDHGB7 protein levels could predict responses to immune checkpoint inhibitors and function as a prognostic marker for PFS.
ConclusionPCDHGB7 expression and methylation are prognostic and immunological biomarkers in non-small cell lung cancer. Plasma PCDHGB7 methylation and protein levels can be used as novel biomarkers for predicting the efficacy of immunotherapy in lung cancer.

研究背景：原钙粘蛋白γ亚家族B7（Protocadherin gamma subfamily B, 7，PCDHGB7）属于原钙粘蛋白家族成员，在神经元连接过程中发挥关键作用，且已被证实与女性生殖系统癌症相关，但其在肺癌中的功能尚未阐明。研究方法：本研究通过公共数据集（人类蛋白质图谱HPA、癌症基因组图谱TCGA、基因表达综合数据库GEO、OncoDB以及MEXPRESS），全面分析了PCDHGB7的表达水平、预后价值、生物学功能、甲基化模式，以及其与肿瘤免疫浸润和免疫治疗应答的关联。本研究纳入本临床中心的两项肺癌免疫治疗队列，以检测血浆中PCDHGB7的甲基化与蛋白水平的关联，及其与免疫治疗结局的关系。研究结果：PCDHGB7在肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）中均呈低表达，且与肿瘤预后相关。PCDHGB7的表达与抑制性免疫细胞呈正相关，而与肿瘤突变负荷（TMB）和同源重组缺陷（HRD）呈负相关。肿瘤组织中PCDHGB7的甲基化水平升高，且与PCDHGB7的mRNA表达水平呈负相关。在免疫治疗队列分析中，肿瘤组织PCDHGB7高表达的患者预后更差。基线血浆中PCDHGB7高甲基化的患者无进展生存期（PFS）和总生存期（OS）更短，而血浆PCDHGB7甲基化水平早期下降的患者预后最佳。血浆PCDHGB7蛋白水平可预测免疫检查点抑制剂的治疗应答，并可作为无进展生存期的预后标志物。研究结论：PCDHGB7的表达与甲基化可作为非小细胞肺癌的预后及免疫学生物标志物。血浆PCDHGB7的甲基化水平与蛋白水平可作为预测肺癌免疫治疗疗效的新型生物标志物。