Zhuo Chuanjun, Shao Mingjing, Chen Ce, Lin Chongguang, Jiang Deguo, Chen Guangdong, Tian Hongjun, Wang Lina, Li Jie, Lin Xiaodong
Tianjin Anding Hospital, Tianjin, China.
Cell Physiol Biochem. 2016;39(4):1537-52. doi: 10.1159/000447856. Epub 2016 Sep 12.
Since gastric cancer (GC) cells exhibited higher grades of SHP-2 encoded by PTPN11 than normal cells, it would be intriguing to explore whether PTPN11 single nucleotide polymorphisms (SNPs) would influence chemotherapy effectiveness and GC prognosis among a Chinese population.
Altogether 430 late-stage GC patients and 960 healthy controls matched with age and sex were incorporated. Three PTPN11 SNPs (i.e. rs7958372, rs12229892 and rs2301756) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chemotherapies of cisplatin and 5-fluorouracil were performed for 4 cycles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the logistic regression. Survival curves were plotted with Kaplan-Meier method and the COX proportional hazard model was used to analyze independent factors for GC prognosis.
For rs12229892, AA and GA genotypes would cause 1.60-fold increase of GC risk in comparison to homozygote GG (OR = 1.60; 95% CI = 1.23-2.07; P < 0.001). The A allele of rs2301756 was significantly associated with a decrease in the risk of GC when compared with G allele (OR = 0.81; 95% CI = 0.65-0.99; P = 0.043). Results from both 2-cycle and 4-cycle chemotherapy suggested that chemotherapy was significantly more effective for GA and AA genotypes of rs2301756 compared with homozygote GG (P < 0.001). Besides, the joint impact of rs12229892 (AA) and environmental factors (i.e. smoking, family history, intake of processed food and H .pylori infection) on GC risk was considered as positive interaction, while that of rs2301756 (AA) and the above parameters was deemed as negative interaction. Finally, differentiation degree, axillary lymph node metastasis, rs12229892 and rs2301756 appeared as independent risk factors for GC development (all P < 0.05).
Since rs2301756 polymorphism of PTPN11 was associated with reduced risk of GC and better effects of chemotherapy on GC, it can be considered as a predictor of GC prognosis and the treatment target for GC.
由于胃癌（GC）细胞中由PTPN11编码的SHP-2水平高于正常细胞，因此探究PTPN11单核苷酸多态性（SNP）是否会影响中国人群的化疗效果和GC预后将是很有意思的。
纳入430例晚期GC患者和960例年龄和性别匹配的健康对照。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对3个PTPN11 SNP（即rs7958372、rs12229892和rs2301756）进行基因分型。采用顺铂和5-氟尿嘧啶进行4个周期的化疗。使用逻辑回归计算比值比（OR）和95%置信区间（CI）。用Kaplan-Meier法绘制生存曲线，并使用COX比例风险模型分析GC预后的独立因素。
对于rs12229892，与纯合子GG相比，AA和GA基因型会使GC风险增加1.60倍（OR = 1.60；95%CI = 1.23 - 2.07；P < 0.001）。与G等位基因相比，rs2301756的A等位基因与GC风险降低显著相关（OR = 0.81；95%CI = 0.65 - 0.99；P = 0.043）。2周期和4周期化疗的结果均表明，与纯合子GG相比，rs2301756的GA和AA基因型化疗效果显著更好（P < 0.001）。此外，rs12229892（AA）与环境因素（即吸烟、家族史、加工食品摄入和幽门螺杆菌感染）对GC风险的联合影响被认为是正相互作用，而rs2301756（AA）与上述参数的联合影响被认为是负相互作用。最后，分化程度、腋窝淋巴结转移、rs12229892和rs2301756是GC发生的独立危险因素（均P < 0.05）。
由于PTPN11的rs2301756多态性与GC风险降低及GC化疗效果较好相关，因此可将其视为GC预后的预测指标和GC的治疗靶点。
