丙酮酸激酶 M2 同工酶的过表达是印戒细胞胃癌的不良预后因素。
Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer.
机构信息
Department of Medical Oncology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul 135-720, South Korea.
出版信息
World J Gastroenterol. 2012 Aug 14;18(30):4037-43. doi: 10.3748/wjg.v18.i30.4037.
AIM
To investigate M2 isoform of pyruvate kinase (PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.
METHODS
All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment. Clinical and pathological information were obtained from the medical records. Gene expression microarray data from 60 cancer and 19 non-cancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA. Tissue microarrays were constructed from 368 gastric cancer patients. Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity. Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated.
RESULTS
PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients (log transformed expression level: 7.6 ± 0.65 vs 6.3 ± 0.51, P < 0.001). Moreover, differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers (log transformed expression level: 7.8 ± 0.70 vs 6.7 ± 0.71, P < 0.001). PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368 (39.1%) human gastric cancer cases. PKM2 expression was not related with stage (P = 0.811), but strongly correlated with gastric cancer differentiation (P < 0.001). Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones. Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells; in contrast, signet-ring cell cancers showed only 17.7% PKM2-positive cells. Importantly, PKM2 expression was correlated with shorter overall survival (P < 0.05) independent of stage only in signet-ring cell cancers.
CONCLUSION
PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas. Its function and potential as a prognostic marker should be further verified in gastric cancer.
目的
研究丙酮酸激酶 M2 同工酶（PKM2）在胃癌中的表达，评估其作为预后生物标志物和抗癌靶点的潜力。
方法
所有组织样本均来自接受根治性胃切除术作为主要治疗的胃癌患者。临床和病理信息来自病历。分析来自 60 例癌症和 19 例非癌症胃组织的基因表达微阵列数据，以评估 PKM2 mRNA 的表达水平。从 368 例胃癌患者中构建组织微阵列。免疫组织化学用于测量 PKM2 表达，通过 PKM2 阳性肿瘤细胞的比例和染色强度确定 PKM2 阳性癌症。评估 PKM2 表达与临床病理因素的相关性，并评估 PKM2 与癌症预后的相关性。
结果
与同一患者的相邻正常组织相比，原发性胃癌中 PKM2 mRNA 水平增加了两倍以上（对数转换表达水平：7.6 ± 0.65 对 6.3 ± 0.51，P < 0.001）。此外，分化型癌症的 PKM2 mRNA 水平明显高于未分化型癌症（对数转换表达水平：7.8 ± 0.70 对 6.7 ± 0.71，P < 0.001）。PKM2 蛋白主要定位于原发性癌细胞的细胞质中，在 368 例人类胃癌病例中的 144 例（39.1%）中检测到。PKM2 表达与分期无关（P = 0.811），但与胃癌分化密切相关（P < 0.001）。分化型癌症表达的 PKM2 蛋白多于未分化型癌症。高分化腺癌显示 63.6%的 PKM2 阳性细胞；相比之下，印戒细胞癌仅显示 17.7%的 PKM2 阳性细胞。重要的是，仅在印戒细胞癌中，PKM2 表达与较短的总生存期相关（P < 0.05），与分期无关。
结论
PKM2 表达可能是印戒细胞癌的不良预后因素。其功能和作为预后标志物的潜力应在胃癌中进一步验证。
Zotero 插件