Department of Biomolecular Sciences (DiSB), University of Urbino "Carlo Bo", Via Arco d'Augusto, 2, 61032, Fano, PU, Italy.
Department of Onco-Hematology, Division of Oncology, Azienda Ospedaliera "Ospedali Riuniti Marche Nord", 61122, Pesaro, Italy.
Gastric Cancer. 2020 Nov;23(6):1064-1074. doi: 10.1007/s10120-020-01078-0. Epub 2020 May 5.
For energy production, cancer cells maintain a high rate of glycolysis instead of oxidative phosphorylation converting glucose into lactic acid. This metabolic shift is useful to survive in unfavorable microenvironments. We investigated whether a positive glycolytic profile (PGP) in gastric adenocarcinomas may be associated with unfavorable outcomes under an anticancer systemic therapy, including the anti-angiogenic ramucirumab.
Normal mucosa (NM) and primary tumor (PT) of 40 metastatic gastric adenocarcinomas patients who received second-line paclitaxel-ramucirumab (PR) were analyzed for mRNA expression of the following genes: HK-1, HK-2, PKM-2, LDH-A, and GLUT-1. Patients were categorized with PGP when at least a doubling of mRNA expression (PT vs. NM) in all glycolytic core enzymes (HK-1 or HK-2, PKM-2, LDH-A) was observed. PGP was also related to TP53 mutational status.
Mean LDH-A, HK-2, PKM-2 mRNA expression levels were significantly higher in PT compared with NM. 18 patients were classified as PGP, which was associated with significantly worse progression-free and overall survival times. No significant association was observed between PGP and clinical-pathologic features, including TP53 positive mutational status, in 28 samples.
Glycolytic proficiency may negatively affect survival outcomes of metastatic gastric cancer patients treated with PR systemic therapy. TP53 mutational status alone does not seem to explain such a metabolic shift.
为了产生能量，癌细胞维持着高糖酵解率，而不是将葡萄糖转化为乳酸的氧化磷酸化。这种代谢转变有助于在不利的微环境中存活。我们研究了胃腺癌中是否存在阳性糖酵解谱（PGP），这种谱是否与包括抗血管生成药物 ramucirumab 在内的抗癌系统治疗的不良结局有关。
分析了 40 例接受二线紫杉醇-ramucirumab（PR）治疗的转移性胃腺癌患者的正常黏膜（NM）和原发肿瘤（PT）的以下基因的 mRNA 表达：HK-1、HK-2、PKM-2、LDH-A 和 GLUT-1。当所有糖酵解核心酶（HK-1 或 HK-2、PKM-2、LDH-A）的 mRNA 表达（PT 与 NM）至少增加两倍时，患者被归类为 PGP。PGP 还与 TP53 突变状态有关。
与 NM 相比，PT 中的平均 LDH-A、HK-2 和 PKM-2 mRNA 表达水平显著更高。18 例患者被归类为 PGP，与无进展生存期和总生存期显著缩短相关。在 28 个样本中，PGP 与临床病理特征（包括 TP53 阳性突变状态）之间未观察到显著相关性。
糖酵解能力可能会对接受 PR 系统治疗的转移性胃腺癌患者的生存结果产生负面影响。TP53 突变状态似乎不能单独解释这种代谢转变。
