Yoon Shinkyo, Kim Jong Gwang, Seo An Na, Park Soo Yeun, Kim Hye Jin, Park Jun Seok, Choi Gyu Seog, Jeong Ji Yun, Jun Do Youn, Yoon Ghil Suk, Kang Byung Woog
Department of Oncology/Hematology, Kyungpook National University School of Medicine, Daegu, South Korea.
Oncology. 2015;89(6):351-9. doi: 10.1159/000439571. Epub 2015 Oct 7.
Recently, enzymes of the serine synthetic pathway (SSP) have been suggested as key player in the metabolic adaptation of oncogenesis. We assessed the expression of enzymes of the SSP in colonic tumor tissue (TT) and paired normal tissue (pNT) and the prognostic implications.
From 2006 to 2010, we included 486 patients with colon cancer who underwent curative surgery at Kyungpook National University Hospital. Phosphoglycerate dehydrogenase (PHGDH), pyruvate dehydrogenase kinase (PDK) 1, PDK2, pyruvate kinase M2 (PKM2), and phosphoserine aminotransferase (PSAT) expression were investigated by immunohistochemical staining (IHC) in TT and pNT. The IHC values were calculated by multiplying intensity by proportion. The final score was classified as follows: 0-2 as negative and 3-12 as positive.
During the median follow-up duration of 55.5 months (37.4-90.6), 78 patients experienced recurrence. The expression of PHGDH, PDK1, and PSAT was significantly higher in TT than pNT (p < 0.001 for each). The univariate analysis for relapse-free survival revealed that TT PDK2 positivity was the only positive prognostic factor (p = 0.023). However, the expression of TT PDK2 did not represent a prognostic value in multivariate analysis.
In conclusion, PHGDH, PDK1, and PSAT were significantly increased in colonic TT compared with pNT. The prognostic implication of these enzymes needs to be further investigated.
最近，丝氨酸合成途径（SSP）的酶被认为是肿瘤发生代谢适应的关键参与者。我们评估了SSP的酶在结肠肿瘤组织（TT）和配对正常组织（pNT）中的表达及其预后意义。
2006年至2010年，我们纳入了486例在庆北国立大学医院接受根治性手术的结肠癌患者。通过免疫组织化学染色（IHC）研究TT和pNT中磷酸甘油酸脱氢酶（PHGDH）、丙酮酸脱氢酶激酶（PDK）1、PDK2、丙酮酸激酶M2（PKM2）和磷酸丝氨酸转氨酶（PSAT）的表达。IHC值通过强度乘以比例来计算。最终评分分类如下：0-2分为阴性，3-12分为阳性。
在中位随访期55.5个月（37.4-90.6）内，78例患者出现复发。TT中PHGDH、PDK1和PSAT的表达明显高于pNT（每项p<0.001）。无复发生存的单因素分析显示，TT中PDK2阳性是唯一的阳性预后因素（p=0.023）。然而，在多因素分析中，TT中PDK2的表达不具有预后价值。
总之，与pNT相比，结肠TT中PHGDH、PDK1和PSAT明显升高。这些酶的预后意义需要进一步研究。
