Ito Chie, Nishizuka Satoshi S, Ishida Kazuyuki, Uesugi Noriyuki, Sugai Tamotsu, Tamura Gen, Koeda Keisuke, Sasaki Akira
Molecular Therapeutics Laboratory, Iwate Medical University School of Medicine, Iwate, Japan; Department of Surgery, Iwate Medical University School of Medicine, Iwate, Japan.
Molecular Therapeutics Laboratory, Iwate Medical University School of Medicine, Iwate, Japan; Department of Surgery, Iwate Medical University School of Medicine, Iwate, Japan; Division of Biomedical Research and Development, Institute of Biomedical Science, Iwate Medical University, Iwate, Japan.
J Surg Res. 2017 May 15;212:195-204. doi: 10.1016/j.jss.2017.01.018. Epub 2017 Jan 30.
Although surgery and chemotherapy have extended advanced gastric cancer patient survival, some patients still experience relapse and metastasis. We postulated that PI3K pathway proteins could be prognostic biomarkers for the advanced gastric cancer patients.
A retrospective cohort of 160 advanced gastric cancer patients receiving potentially curative surgery with/without chemotherapy was investigated for PIK3CA mutation and PI3K pathway protein level in the context of overall survival and relapse-free survival.
Thirteen patients (13 of 111, 11.7%) had PIK3CA mutations in codon 545, whereas one patient (1 of 94, 1.1%) had a mutation in PIK3CA codon 1047. PI3K pathway protein immunohistochemistry demonstrated that phosphorylated AKT positive [p-AKT (+)] patients in the surgery-only group had a good prognosis in terms of overall survival and relapse-free survival. No significant association between PIK3CA mutations and PI3K pathway protein level was seen.
This study revealed that (1) PIK3CA hotspot mutations occurred with low frequency in gastric cancer; (2) PIK3CA hotspot mutations were not directly associated with PI3K pathway activation; and (3) p-AKT (+) may be a biomarker for better outcomes for gastric cancer patients undergoing gastrectomy regardless of the PIK3CA mutation status.
尽管手术和化疗延长了晚期胃癌患者的生存期，但仍有一些患者出现复发和转移。我们推测PI3K通路蛋白可能是晚期胃癌患者的预后生物标志物。
对160例接受了有/无化疗的潜在根治性手术的晚期胃癌患者进行回顾性队列研究，在总生存期和无复发生存期的背景下，研究PIK3CA突变和PI3K通路蛋白水平。
13例患者（111例中的13例，11.7%）在密码子545处发生PIK3CA突变，而1例患者（94例中的1例，1.1%）在PIK3CA密码子1047处发生突变。PI3K通路蛋白免疫组化显示，单纯手术组中磷酸化AKT阳性[p-AKT(+)]的患者在总生存期和无复发生存期方面预后良好。未观察到PIK3CA突变与PI3K通路蛋白水平之间存在显著关联。
本研究表明：（1）PIK3CA热点突变在胃癌中发生率较低；（2）PIK3CA热点突变与PI3K通路激活无直接关联；（3）无论PIK3CA突变状态如何，p-AKT(+)可能是接受胃切除术的胃癌患者预后较好的生物标志物。
