Dipartimento di Scienze Biomediche per la Salute, Università degli Studi Di Milano, Via F.lli Cervi 93, Segrate, Milan 20090, Italy; IRCCS Policlinico San Donato, Piazza Edmondo Malan, San Donato Milanese, Milan 20097, Italy.
Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica, via Fantoli 16/15, Milan 20138, Italy.
Clin Chim Acta. 2015 Jan 15;439:42-9. doi: 10.1016/j.cca.2014.10.003. Epub 2014 Oct 12.
Prostate cancer (PCa) is the second cause of mortality in men worldwide. The prostate-specific antigen (PSA) test is routinely adopted in diagnosis; nevertheless more reliable biomarkers are continuously under investigation by monitoring the release of molecules into the bloodstream. The serum protein profiles appear to provide cancer-specific fingerprints that help to discriminate patients (especially with low PSA level) from controls, improving the performance of existing clinical tests.
Samples from healthy controls and PCa patients with low (≤4 ng/mL) and high PSA (>4 ng/mL) levels were analyzed by MALDI profiling, and by a multi fractionation approach coupled to ESI-MS for peaks identification.
MALDI profiling achieved to detect 10 and 14 changed peaks (p-value <0.05), respectively, in PCa patients with low and high PSA versus controls. In particular, a peak identified as C3f fragment, resulted overexpressed in low PSA PCa patients.
PSA test, coupled to MALDI profiling, is able to detect changes, specifically related to PCa, in low molecular weight protein range. Furthermore, for the first time in prostate cancer research, the identification and quantification of the small peptide C3f appears to be relevant for the detection of false negatives, providing an additive diagnostic power to PSA (p<0.01) and suggesting its use in clinical tests.
前列腺癌(PCa)是全球男性死亡的第二大原因。前列腺特异性抗原(PSA)检测被常规用于诊断;然而,人们一直在通过监测分子在血液中的释放来寻找更可靠的生物标志物。血清蛋白谱似乎提供了有助于区分患者(尤其是 PSA 水平较低的患者)与对照的癌症特异性指纹,从而提高了现有临床检测的性能。
通过 MALDI 分析和与 ESI-MS 耦合的多馏分方法对健康对照者和 PSA 水平较低(≤4ng/mL)和较高(>4ng/mL)的 PCa 患者的样本进行分析,以确定峰的鉴定。
MALDI 分析分别在 PSA 水平较低和较高的 PCa 患者与对照者中检测到 10 和 14 个变化峰(p 值<0.05)。特别是,鉴定为 C3f 片段的峰在 PSA 水平较低的 PCa 患者中过度表达。
PSA 检测与 MALDI 分析相结合,能够检测到低分子量蛋白质范围内与 PCa 特异性相关的变化。此外,在前列腺癌研究中首次发现,小肽 C3f 的鉴定和定量似乎与假阴性的检测有关,为 PSA 提供了附加的诊断能力(p<0.01),并提示其在临床检测中的应用。