Department of Tumor Pathology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Cancer Sci. 2013 Oct;104(10):1295-302. doi: 10.1111/cas.12221. Epub 2013 Jul 30.
The identification of cancer biomarkers is critical for target-linked cancer therapy. The overall level of phosphatidylcholine (PC) is elevated in colorectal cancer (CRC). To investigate which species of PC is overexpressed in colorectal cancer, an imaging mass spectrometry was performed using a panel of non-neoplastic mucosal and CRC tissues. In the present study, we identified a novel biomarker, PC(16:0/16:1), in CRC using imaging mass spectrometry. Specifically, elevated levels of PC(16:0/16:1) expression were observed in the more advanced stage of CRC. Our data further showed that PC(16:0/16:1) was specifically localized in the cancer region when examined using imaging mass spectrometry. Notably, because the ratio of PC(16:0/16:1) to lyso-PC(16:0) was higher in CRC, we postulated that lyso-PC acyltransferase (LPCAT) activity is elevated in CRC. In an in vitro analysis, we showed that LPCAT4 is involved in the deregulation of PC(16:0/16:1) in CRC. In an immunohistochemical analysis, LPCAT4 was shown to be overexpressed in CRC. These data indicate the potential usefulness of PC(16:0/16:1) for the clinical diagnosis of CRC and implicate LPCAT4 in the elevated expression of PC(16:0/16:1) in CRC.
癌症生物标志物的鉴定对于靶向癌症治疗至关重要。磷脂酰胆碱 (PC) 的总水平在结直肠癌 (CRC) 中升高。为了研究哪种 PC 物种在结直肠癌中过度表达,使用非肿瘤性黏膜和 CRC 组织的面板进行了成像质谱分析。在本研究中,我们使用成像质谱法鉴定了结直肠癌中的一种新型生物标志物 PC(16:0/16:1)。具体而言,在 CRC 的更晚期观察到 PC(16:0/16:1)表达水平升高。我们的数据进一步表明,当使用成像质谱法检查时,PC(16:0/16:1)特异性定位于癌症区域。值得注意的是,由于 CRC 中 PC(16:0/16:1)与溶血磷脂酰胆碱 (16:0) 的比值更高,我们推测 LPCAT 活性在 CRC 中升高。在体外分析中,我们表明 LPCAT4 参与了 CRC 中 PC(16:0/16:1)的失调。在免疫组织化学分析中,显示 LPCAT4 在 CRC 中过度表达。这些数据表明 PC(16:0/16:1)在 CRC 的临床诊断中具有潜在的用途,并暗示 LPCAT4 参与了 CRC 中 PC(16:0/16:1)的高表达。