Background/Objectives: Prostate-specific membrane antigen (PSMA) is a well-established target in prostate cancer therapy that has shown potential as a theranostic target across non-central nervous system (CNS) and CNS tumor types. We aimed to investigate the pan-tissue expression pattern of the PSMA-encoding gene FOLH1 to assess whether transcriptome profiling can inform tumor diagnostic and theranostic probes. Methods: We assessed FOLH1 expression from the Open Pediatric Cancer Project (OpenPedCan,n= 2132 specimens), the Cancer Genome Atlas (TCGA,n= 10,411 specimens), and the Genotype Tissue Expression Project (GTEx,n= 17,382 specimens) in relation to published reports of PSMA radionuclide uptake in various tumors. Results: When comparing FOLH1 expression across tumor versus normal tissues, we found that non-CNS tumors exhibiting elevated expression of at least two-fold (FDR < 0.05) were reported to have significant PSMA radionuclide uptake in contrast to tumors with less than a two-fold elevation or with lower expression of FOLH1 relative to normal tissues. Notably, CNS tumors universally exhibited lower expression of FOLH1 relative to normal brain tissue, but we observed considerable variation in the expression of blood–tumor barrier (BTB) components associated with reports of BTB integrity and uptake of PSMA radiotracers. Conclusions: Large-scale transcriptomics data may help guide the application of PSMA-based radionuclide therapies in non-CNS tumors, but care should be taken to account for BTB effects in CNS tumors when assessing the potential for radionuclide success. This study demonstrates that FOLH1 showed a lack of tumor-specific expression for both adult and pediatric CNS tumors when compared to normal brain tissue, suggesting that PSMA is not a desirable target in brain tumors.
背景/目的：前列腺特异性膜抗原（PSMA）是前列腺癌治疗中一个公认的靶点，并已显示出作为非中枢神经系统（CNS）和CNS肿瘤类型诊疗一体化靶点的潜力。本研究旨在探究PSMA编码基因FOLH1的全组织表达模式，以评估转录组分析能否为肿瘤诊断和诊疗一体化探针的开发提供信息。方法：我们基于开放儿科癌症项目（OpenPedCan，n=2132例样本）、癌症基因组图谱（TCGA，n=10411例样本）和基因型-组织表达项目（GTEx，n=17382例样本）的数据，评估了FOLH1的表达情况，并将其与已发表的关于PSMA在不同肿瘤中放射性核素摄取的研究报告进行关联分析。结果：在比较肿瘤组织与正常组织的FOLH1表达时，我们发现，相对于正常组织，表达量至少升高两倍（错误发现率FDR < 0.05）的非CNS肿瘤，据报道具有显著的PSMA放射性核素摄取；而表达升高不足两倍或表达量低于正常组织的肿瘤则不然。值得注意的是，相对于正常脑组织，所有CNS肿瘤的FOLH1表达均较低，但我们观察到与血-肿瘤屏障（BTB）完整性及PSMA放射性示踪剂摄取相关的BTB成分表达存在显著差异。结论：大规模转录组学数据可能有助于指导基于PSMA的放射性核素疗法在非CNS肿瘤中的应用，但在评估CNS肿瘤中放射性核素治疗成功的潜力时，应谨慎考虑BTB效应。本研究表明，与正常脑组织相比，FOLH1在成人和儿童CNS肿瘤中均缺乏肿瘤特异性表达，这表明PSMA并非脑肿瘤的理想靶点。
肿瘤(癌症)患者之家