Genetic variations in the PI3K/PTEN/AKT/mTOR pathway predict tumor response and disease-free survival in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy and radical surgery.
Genetic variations in the PI3K/PTEN/AKT/mTOR pathway predict tumor response and disease-free survival in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy and radical surgery.
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PI3K/PTEN/AKT/mTOR 通路的遗传变异可预测接受术前放化疗和根治性手术的局部晚期直肠癌患者的肿瘤反应和无病生存期
DOI：
10.7150/jca.23538
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发表时间：
2018
影响因子：
3.9
通讯作者：
Pan Z
中科院分区：
文献类型：
--
作者：
Peng J;Ma W;Zhou Z;Gu Y;Lu Z;Zhang R;Pan Z
目的：虽然术前放化疗（CRT）后全直肠系膜切除术（TME）是局部晚期直肠癌（LARC）的标准治疗方法，但患者的临床疗效不同。本研究旨在确定PI 3 K/PTEN/AKT/mTOR通路的遗传变异与LARC患者临床结局之间的相关性。方法：对5个核心基因（PIK 3CA、PTEN、AKT 1、AKT 2和FRAP 1）的16个标签单核苷酸多态性（SNP）进行基因分型。确定这些SNP与术前CRT的肿瘤反应、术后无病生存期（DFS）和总生存期（OS）的相关性。根据年龄、性别、临床分期、肿瘤分化程度、肿瘤位置、术前化疗周期和CRT完成至手术的时间间隔调整粗比值比（OR）和风险比（HR）。结果如下：在对97例LARC患者的分析中，AKT 1：rs 2498804的G/T+G/G基因型与肿瘤缓解率增加相关（校正OR = 2.909，95%置信区间（CI），1.127-7.505，P = 0.027）。在中位随访65.7个月时，AKT 2：rs 8100018的G/C+C/C基因型与术后复发风险降低相关（校正HR = 0.414; 95%CI，0.187-0.914，P = 0.029）。携带AKT 2：rs 8100018 G/C+C/C基因型的患者5年DFS率高于携带野生型基因型的患者（79.2% vs. 62.3%，P = 0.038）。没有一个SNP与病理完全缓解（pCR）或5年OS显著相关。结论：目前的研究表明，PI 3 K/ PTEN/AKT/mTOR信号通路内的遗传变异与LARC患者接受术前CRT后根治性手术的临床结局相关。
Objective: Although preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer (LARC), the clinical efficacy differs among patients. This study was conducted to determine the association between genetic variations in the PI3K/PTEN/AKT/mTOR pathway and clinical outcomes in LARC patients. Methods: Sixteen tagging single-nucleotide polymorphisms (SNPs) in five core genes (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) were genotyped. The associations of these SNPs with tumor response to preoperative CRT, postoperative disease-free survival (DFS) and overall survival (OS) were identified. Crude odds ratios (ORs) and hazard ratios (HRs) were adjusted by age, sex, clinical stage, tumor differentiation, tumor location, cycles of preoperative chemotherapy and time interval from CRT completion to surgery. Results: In an analysis of 97 LARC patients, the G/T+G/G genotype of AKT1:rs2498804 was associated with an increased tumor response rate (adjusted OR = 2.909, 95% confidence interval (CI), 1.127-7.505, P = 0.027). At a median of 65.7 months of follow-up, the G/C+C/C genotype of AKT2:rs8100018 was associated with a reduced risk of postoperative recurrence (adjusted HR = 0.414; 95% CI, 0.187-0.914, P = 0.029). Patients carrying the G/C+C/C genotype in AKT2:rs8100018 presented a higher 5-year DFS rate than those with the wild-type genotype (79.2% vs. 62.3%, P = 0.038). None of the SNPs were significantly associated with pathological complete response (pCR) or 5-year OS. Conclusions: The current study indicates that genetic variations within the PI3K/ PTEN/AKT/mTOR signaling pathway are associated with the clinical outcomes of LARC patients undergoing preoperative CRT followed by radical surgery.
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影响因子：
3.4
作者：
Li, Jian;Dang, Yunzhi;Shen, Lin
通讯作者：
Shen, Lin
影响因子：
1.6
作者：
Lin, J. Z.;Zeng, Z. F.;Pan, Z. Z.
通讯作者：
Pan, Z. Z.
影响因子：
5.3
作者：
Kim, Jung-Sik;Xu, Xuehua;Waldman, Todd
通讯作者：
Waldman, Todd
影响因子：
--
作者：
Chappell WH;Steelman LS;Long JM;Kempf RC;Abrams SL;Franklin RA;Bäsecke J;Stivala F;Donia M;Fagone P;Malaponte G;Mazzarino MC;Nicoletti F;Libra M;Maksimovic-Ivanic D;Mijatovic S;Montalto G;Cervello M;Laidler P;Milella M;Tafuri A;Bonati A;Evangelisti C;Cocco L;Martelli AM;McCubrey JA
通讯作者：
McCubrey JA
影响因子：
--
作者：
McCubrey JA;Steelman LS;Chappell WH;Abrams SL;Franklin RA;Montalto G;Cervello M;Libra M;Candido S;Malaponte G;Mazzarino MC;Fagone P;Nicoletti F;Bäsecke J;Mijatovic S;Maksimovic-Ivanic D;Milella M;Tafuri A;Chiarini F;Evangelisti C;Cocco L;Martelli AM
通讯作者：
Martelli AM