Cui Rong, Shi Xing-Yao
Department of Gastrointestinal Surgery, Jiading Hospital of Traditional Chinese Medicine Shanghai 201800, P. R. China.
Int J Clin Exp Pathol. 2015 Sep 1;8(9):11393-9. eCollection 2015.
Reprogrammed metabolism is a hallmark of cancer cells. Pyruvate kinase isozyme type M2 (PKM2), which is frequently up-regulated in multiple human malignancies, has been demonstrated to play a critical function in glucose metabolism, gene transcription and tumorigenesis. However, limited knowledge is known about the expression pattern and prognostic value of PKM2 in colorectal cancer (CRC). In this study, we first observed that the mRNA level of PKM2 is commonly up-regulated in CRC tissues compared with their normal counterparts as demonstrated by data derived from Oncomine database. Similar results were also found in 32 paired CRC tumor and non-tumor specimens in our cohort and 4 CRC cell lines. Furthermore, by a large scale of immunohistochemical analysis in a tissue microarray containing 345 cases of CRC specimens, we demonstrated that the protein expression of PKM2 expression is up-regulated in 79.4% (274/345) samples detected and elevated PKM2 expression is closely correlated with enhanced TNM stage and higher serum CEA level. Meanwhile, Kaplan-Meier survival analysis showed that CRC patients with a higher PKM2 expression have a poorer clinical outcome than those with a lower PKM2 expression. Multivariate Cox regression analysis revealed that PKM2 and TNM stage are two independent prognostic factors for overall survival rate of CRC patients. Taken together, our studies reveal the prognostic value of PKM2 in CRC and support that PKM2 may act as a molecular target for CRC treatment.
代谢重编程是癌细胞的一个标志。丙酮酸激酶M2型同工酶(PKM2)在多种人类恶性肿瘤中经常上调,已被证明在葡萄糖代谢、基因转录和肿瘤发生中起关键作用。然而,关于PKM2在结直肠癌(CRC)中的表达模式和预后价值的了解有限。在本研究中,我们首先观察到,根据Oncomine数据库的数据,与正常组织相比,PKM2的mRNA水平在CRC组织中普遍上调。在我们队列中的32对CRC肿瘤和非肿瘤标本以及4种CRC细胞系中也发现了类似结果。此外,通过对包含345例CRC标本的组织芯片进行大规模免疫组化分析,我们证明在检测的样本中,79.4%(274/345)的PKM2蛋白表达上调,并且PKM2表达升高与TNM分期增加和血清CEA水平升高密切相关。同时,Kaplan-Meier生存分析表明,PKM2表达较高的CRC患者的临床结局比PKM2表达较低的患者更差。多变量Cox回归分析显示,PKM2和TNM分期是CRC患者总生存率的两个独立预后因素。综上所述,我们的研究揭示了PKM2在CRC中的预后价值,并支持PKM2可能作为CRC治疗的分子靶点。