Increased Expression of PHGDH and Prognostic Significance in Colorectal Cancer.
Increased Expression of PHGDH and Prognostic Significance in Colorectal Cancer.
复制标题
PHGDH表达的增加和结直肠癌的预后意义。
DOI：
10.1016/j.tranon.2016.03.006
复制
发表时间：
2016-06
影响因子：
5
通讯作者：
Qiang JF
中科院分区：
文献类型：
--
作者：
Jia XQ;Zhang S;Zhu HJ;Wang W;Zhu JH;Wang XD;Qiang JF
磷酸甘油酸脱氢酶（PHGDH）在癌症特异性代谢重编程中起重要作用。据报道，它是几种人类恶性肿瘤（如乳腺癌和黑色素瘤）中假定的代谢性致癌基因。迄今为止，PHGDH在结直肠癌（CRC）中的表达及其与临床病理特征和预后的关系仍未确定。在本研究中，我们使用组织微阵列免疫组化（TMA-IHC）检测了193对福尔马林固定、石蜡包埋的结直肠癌及邻近组织标本、25例慢性结肠炎、41例低级别和19例高级别上皮内瘤变标本的PHGDH蛋白表达，并使用定量反转录PCR （qRT-PCR）检测了另外23对新鲜结直肠癌及邻近组织的PHGDH mRNA水平。我们发现，与匹配的邻近非肿瘤组织相比，肿瘤组织中PHGDH mRNA和蛋白均高表达，且PHGDH蛋白高表达与TNM分期晚期（P = 0.038）和肿瘤较大（P = 0.001）相关。多因素Cox回归分析显示，PHGDH蛋白表达（HR = 2.285, 95% CI = 1.18 ~ 4.41, P = 0.014）、肿瘤分化（HR = 0.307, 95% CI = 0.154 ~ 0.609, P = 0.001）、TNM分期（HR = 1.791, 95% CI = 1.125 ~ 2.85, P = 0.014）是结直肠癌的独立预后因素。Kaplan-Meier生存曲线和log rank检验显示，高PHGDH蛋白表达导致结直肠癌患者预后不良（P < 0.001）。总之，这些结果表明，评估PHGDH的表达可能有助于识别CRC的高危亚组。
Phosphoglycerate dehydrogenase (PHGDH) plays an essential role in cancer-specific metabolic reprogramming. It has been reported as a putative metabolic oncogene in several types of human malignant tumors, such as breast cancer and melanoma. To date, PHGDH expression in colorectal cancer (CRC) as well as its association with clinicopathological characteristics and prognostic implication remain undetermined. In this study, we determined the PHGDH protein expression using tissue microarray immunohistochemistry (TMA-IHC) on 193 pairs of formalin-fixed, paraffin-embedded specimens of CRC and adjacent tissues, 25 chronic colitis, 41 low-, and 19 high-grade intraepithelial neoplasia specimens, and we also determined PHGDH mRNA level using quantitative reverse transcription PCR (qRT-PCR) on additional 23 pairs of fresh CRC tissues and adjacent tissues. We found that both PHGDH mRNA and protein was highly expressed in tumor tissues in comparison with matched adjacent non-tumor tissues, and high PHGDH protein expression was correlated with advanced TNM stage (P = .038) and larger tumor (P = .001). Multivariate Cox regression analysis showed that PHGDH protein expression (HR = 2.285, 95% CI = 1.18 to 4.41, P = .014), tumor differentiation (HR = .307, 95% CI = .154 to 0.609, P = .001), and TNM stage (HR = 1.791, 95% CI = 1.125 to 2.85, P = .014) were independent prognostic factors in CRC. Kaplan-Meier survival curves and log rank test showed that high PHGDH protein expression contributed to poor outcome in CRC patients (P < .001). In conclusion, these results suggest that assessment of PHGDH expression could be useful in identifying a high-risk subgroup of CRC.