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Abstract：
Glioma pathogenesis related-2 (GLIPR2), an emerging Golgi membrane protein implicated in autophagy, has received limited attention in current scholarly discourse.
Leveraging extensive datasets, including The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Human Protein Atlas (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC), we conducted a comprehensive investigation into GLIPR2 expression across diverse human malignancies. Utilizing UALCAN, OncoDB, MEXPRESS and cBioPortal databases, we scrutinized GLIPR2 mutation patterns and methylation landscapes. The integration of bulk and single-cell RNA sequencing facilitated elucidation of relationships among cellular heterogeneity, immune infiltration, and GLIPR2 levels in pan-cancer. Employing ROC and KM analyses, we unveiled the diagnostic and prognostic potential of GLIPR2 across diverse cancers. Immunohistochemistry provided insights into GLIPR2 expression patterns in a multicenter cohort spanning various cancer types. In vitro functional experiments, including transwell assays, wound healing analyses, and drug sensitivity testing, were employed to delineate the tumor suppressive role of GLIPR2.
GLIPR2 expression was significantly reduced in neoplastic tissues compared to its prevalence in healthy tissues. Copy number variations (CNV) and alterations in methylation patterns exhibited discernible correlations with GLIPR2 expression within tumor tissues. Moreover, GLIPR2 demonstrated diagnostic and prognostic implications, showing pronounced associations with the expression profiles of numerous immune checkpoint genes and the relative abundance of immune cells in the neoplastic microenvironment. This multifaceted influence was evident across various cancer types, with lung adenocarcinoma (LUAD) being particularly prominent. Notably, patients with LUAD exhibited a significant decrease in GLIPR2 expression within practical clinical settings. Elevated GLIPR2 expression correlated with improved prognostic outcomes specifically in LUAD. Following radiotherapy, LUAD cases displayed an increased presence of GLIPR2+ infiltrating cellular constituents, indicating a notable correlation with heightened sensitivity to radiation-induced therapeutic modalities. A battery of experiments validated the functional role of GLIPR2 in suppressing the malignant phenotype and enhancing treatment sensitivity.
In pan-cancer, particularly in LUAD, GLIPR2 emerges as a promising novel biomarker and tumor suppressor. Its involvement in immune cell infiltration suggests potential as an immunotherapeutic target.
Leveraging extensive datasets, including The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Human Protein Atlas (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC), we conducted a comprehensive investigation into GLIPR2 expression across diverse human malignancies. Utilizing UALCAN, OncoDB, MEXPRESS and cBioPortal databases, we scrutinized GLIPR2 mutation patterns and methylation landscapes. The integration of bulk and single-cell RNA sequencing facilitated elucidation of relationships among cellular heterogeneity, immune infiltration, and GLIPR2 levels in pan-cancer. Employing ROC and KM analyses, we unveiled the diagnostic and prognostic potential of GLIPR2 across diverse cancers. Immunohistochemistry provided insights into GLIPR2 expression patterns in a multicenter cohort spanning various cancer types. In vitro functional experiments, including transwell assays, wound healing analyses, and drug sensitivity testing, were employed to delineate the tumor suppressive role of GLIPR2.
GLIPR2 expression was significantly reduced in neoplastic tissues compared to its prevalence in healthy tissues. Copy number variations (CNV) and alterations in methylation patterns exhibited discernible correlations with GLIPR2 expression within tumor tissues. Moreover, GLIPR2 demonstrated diagnostic and prognostic implications, showing pronounced associations with the expression profiles of numerous immune checkpoint genes and the relative abundance of immune cells in the neoplastic microenvironment. This multifaceted influence was evident across various cancer types, with lung adenocarcinoma (LUAD) being particularly prominent. Notably, patients with LUAD exhibited a significant decrease in GLIPR2 expression within practical clinical settings. Elevated GLIPR2 expression correlated with improved prognostic outcomes specifically in LUAD. Following radiotherapy, LUAD cases displayed an increased presence of GLIPR2+ infiltrating cellular constituents, indicating a notable correlation with heightened sensitivity to radiation-induced therapeutic modalities. A battery of experiments validated the functional role of GLIPR2 in suppressing the malignant phenotype and enhancing treatment sensitivity.
In pan-cancer, particularly in LUAD, GLIPR2 emerges as a promising novel biomarker and tumor suppressor. Its involvement in immune cell infiltration suggests potential as an immunotherapeutic target.
摘要：
■胶质瘤发病机制相关2（GLIPR2），一种新出现的与自噬有关的高尔基膜蛋白，在当前的学术话语中受到的关注有限。
■利用广泛的数据集，包括癌症基因组图谱（TCGA），基因型组织表达（GTEx），人蛋白质图谱(HPA),和临床蛋白质组学肿瘤分析联盟（CPTAC），我们对GLIPR2在不同人类恶性肿瘤中的表达进行了全面调查.利用UALCAN,OncoDB,MEXPRESS和cBioPortal数据库，我们仔细检查了GLIPR2突变模式和甲基化景观。整体和单细胞RNA测序的整合有助于阐明细胞异质性之间的关系，免疫浸润，和GLIPR2在泛癌症中的水平。采用ROC和KM分析，我们揭示了GLIPR2在不同癌症中的诊断和预后潜力.免疫组织化学提供了对跨越各种癌症类型的多中心队列中GLIPR2表达模式的见解。体外功能实验，包括transwell分析，伤口愈合分析，和药物敏感性测试，用于描述GLIPR2的肿瘤抑制作用。
■与在健康组织中的患病率相比，GLIPR2在肿瘤组织中的表达显着降低。拷贝数变异（CNV）和甲基化模式的改变显示出与肿瘤组织内GLIPR2表达的明显相关性。此外，GLIPR2具有诊断和预后意义，显示与许多免疫检查点基因的表达谱和肿瘤微环境中免疫细胞的相对丰度明显相关。这种多方面的影响在各种癌症类型中都很明显，肺腺癌（LUAD）尤为突出。值得注意的是,在实际临床环境中,LUAD患者的GLIPR2表达显著下降.升高的GLIPR2表达与改善的预后结果相关，特别是在LUAD中。放疗后，LUAD病例显示GLIPR2+浸润细胞成分的存在增加，表明与对辐射诱导的治疗方式的敏感性提高显着相关。一系列实验验证了GLIPR2在抑制恶性表型和增强治疗敏感性方面的功能作用。
■在泛癌症中，特别是在LUAD，GLIPR2作为一种有前途的新型生物标志物和肿瘤抑制剂出现。其参与免疫细胞浸润表明作为免疫治疗靶标的潜力。
■利用广泛的数据集，包括癌症基因组图谱（TCGA），基因型组织表达（GTEx），人蛋白质图谱(HPA),和临床蛋白质组学肿瘤分析联盟（CPTAC），我们对GLIPR2在不同人类恶性肿瘤中的表达进行了全面调查.利用UALCAN,OncoDB,MEXPRESS和cBioPortal数据库，我们仔细检查了GLIPR2突变模式和甲基化景观。整体和单细胞RNA测序的整合有助于阐明细胞异质性之间的关系，免疫浸润，和GLIPR2在泛癌症中的水平。采用ROC和KM分析，我们揭示了GLIPR2在不同癌症中的诊断和预后潜力.免疫组织化学提供了对跨越各种癌症类型的多中心队列中GLIPR2表达模式的见解。体外功能实验，包括transwell分析，伤口愈合分析，和药物敏感性测试，用于描述GLIPR2的肿瘤抑制作用。
■与在健康组织中的患病率相比，GLIPR2在肿瘤组织中的表达显着降低。拷贝数变异（CNV）和甲基化模式的改变显示出与肿瘤组织内GLIPR2表达的明显相关性。此外，GLIPR2具有诊断和预后意义，显示与许多免疫检查点基因的表达谱和肿瘤微环境中免疫细胞的相对丰度明显相关。这种多方面的影响在各种癌症类型中都很明显，肺腺癌（LUAD）尤为突出。值得注意的是,在实际临床环境中,LUAD患者的GLIPR2表达显著下降.升高的GLIPR2表达与改善的预后结果相关，特别是在LUAD中。放疗后，LUAD病例显示GLIPR2+浸润细胞成分的存在增加，表明与对辐射诱导的治疗方式的敏感性提高显着相关。一系列实验验证了GLIPR2在抑制恶性表型和增强治疗敏感性方面的功能作用。
■在泛癌症中，特别是在LUAD，GLIPR2作为一种有前途的新型生物标志物和肿瘤抑制剂出现。其参与免疫细胞浸润表明作为免疫治疗靶标的潜力。
