Correlations of highly-expressed purinergic ligand-gated ion channel 7 purine receptor with clinicopathological features and prognosis in patients with resectable non-small cell lung cancer
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摘要:目的
分析嘌呤能型2受体家族X7嘌呤受体(P2X7R)表达与可切除非小细胞肺癌(NSCLC)患者临床病理特征及预后的关系。
方法选取120例NSCLC患者肿瘤组织标本, 其中67例组织标本包含癌旁正常肺组织。分析P2X7R表达情况与临床病理特征的相关性; 采用Logistic回归模型和Kaplan-Meier生存曲线评估P2X7R表达情况对NSCLC患者生存预后的预测价值。
结果NSCLC组织中P2X7R阳性表达率高于癌旁正常组织, 差异有统计学意义(P < 0.01);TNM分期Ⅲ期、淋巴结状态N1或N2期、肿瘤直径≥3 cm及CD8+肿瘤浸润性淋巴细胞(TILs)低密度的NSCLC患者的P2X7R高表达率更高, 差异有统计学意义(P < 0.05或P < 0.01);P2X7R低表达者5年无病生存率和总生存率均高于P2X7R高表达者, 差异有统计学意义(P < 0.01)。Cox回归分析显示, NSCLC组织P2X7R表达是5年无病生存率和总生存率的独立预后影响因子(P < 0.05)。NSCLC组织中P2X7R表达预测5年复发或转移、总生存期的受试者工作特征曲线的曲线下面积分别为0.850(95%CI: 0.770~0.930)、0.780(95%CI: 0.696~0.864)。
结论P2X7R可作为NSCLC可靠的预后指标和潜在的治疗靶点。
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关键词:
- 嘌呤能型2受体家族X7嘌呤受体 /
- 非小细胞肺癌 /
- 临床病理特征 /
- 总生存期 /
- 无病生存率
Abstract:ObjectiveTo analyze the correlations of highly-expressed purinergic ligand-gated ion channel 7 purine receptor (P2X7R) with clinicopathological features and prognosis in patients with resectable non-small cell lung cancer (NSCLC).
MethodsA total of 120 specimens of tumor tissue were selected in patients with NSCLC, of which 67 tissue specimens contained adjacent normal lung tissues.The correlation between P2X7R expression and clinicopathological features was analyzed; the Logistic regression model and Kaplan-Meier survival curve were used to evaluate the value of P2X7R expression in predicting the survival and prognosis of NSCLC patients.
ResultsThe positive expression rate of P2X7R in the NSCLC tissues was significantly higher than that in adjacent normal tissues (P < 0.01);the high expression rate of P2X7R was significantly higher in the NSCLC patients with phase Ⅲ of TNM staging, phase N1 or N2 of lymph node status, tumor diameter≥3 cm and low density of CD8+ tumour-infiltrating lymphocytes (TILs)(P < 0.05 or P < 0.01);the 5-year disease-free survival and overall survival of patients with low expression of P2X7R were significantly higher than those with high expression of P2X7R (P < 0.01).Cox regression analysis showed that the expression of P2X7R in NSCLC tissues was an independent prognostic influencing factor for 5-year disease-free survival and overall survival (P < 0.05).The areas under the curve of the receiver operating characteristic curve of P2X7R expression in NSCLC tissues for prediction of 5-year recurrence or metastasis and overall survival were 0.850(95%CI, 0.770 to 0.930) and 0.780(95%CI, 0.696 to 0.864) respectively.
ConclusionP2X7R can be used as a reliable prognostic index and potential therapeutic target for NSCLC.
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图 1 NSCLC组织中P2X7R及CD8+ TILs的免疫组化结果
A: P2X7R强阳性表达; B: P2X7R阴性表达; C: CD8+ TILs高密度; D: CD8+ TILs低密度。
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图 2 P2X7R表达与NSCLC患者生存情况的Kaplan-Meier生存曲线
A: P2X7R低表达与高表达者无病生存期的比较; B: P2X7R低表达与高表达者总生存期的比较。
表 1 NSCLC组织中P2X7R表达与临床病理特征的关系[n(%)]
指标 分类 n P2X7R表达 χ2 P 低表达(n=57) 高表达(n=63) 年龄 < 60岁 67 34(50.75) 33(49.25) 0.641 0.423 ≥60岁 53 23(43.40) 30(56.60) 性别 男 88 44(50.00) 44(50.00) 0.827 0.363 女 32 13(40.63) 19(59.38) TNM分期 Ⅰ~Ⅱ期 91 51(56.04) 40(43.96) 11.021 < 0.001 Ⅲ期 29 6(20.69) 23(79.31) 淋巴结状态 N0期 60 37(61.67) 23(38.33) 9.657 0.002 N1或N2期 60 20(33.33) 40(66.67) 分化程度 低或未分化 32 12(37.50) 20(62.50) 1.895 0.388 中 57 30(52.63) 27(47.37) 高 31 15(48.39) 16(51.61) 吸烟史 是 36 21(58.33) 15(41.67) 2.420 0.120 否 84 36(42.86) 48(57.14) 肿瘤直径 < 3 cm 51 31(60.78) 20(39.22) 6.277 0.012 ≥3 cm 69 26(37.68) 43(62.32) 病理类型 鳞癌 70 37(52.86) 33(47.14) 1.933 0.390 腺癌 50 20(40.00) 30(60.00) CD8+ TILs密度 低 88 27(30.68) 61(69.32) 37.431 < 0.001 高 32 30(93.75) 2(6.25) P2X7R: 2型嘌呤能受体家族嘌呤能离子通道型7受体; TILs: 肿瘤浸润性淋巴细胞。 
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表 2 单因素分析影响NSCLC患者预后不良的预后因素
变量 无病生存 总生存 OR(95%CI) P OR(95%CI) P 年龄 1.017(0.991~1.044) 0.205 1.009(0.985~1.034) 0.458 性别 0.404(0.150~1.085) 0.072 0.600(0.259~1.393) 0.235 吸烟史 0.629(0.277~1.428) 0.267 0.418(0.188~0.927) 0.032 组织学类型 0.832(0.383~1.809) 0.643 1.098(0.527~2.285) 0.803 组织分化程度 1.049(0.745~1.477) 0.786 1.199(0.868~1.658) 0.271 TNM分期 1.482(0.869~2.528) 0.149 4.136(2.230~7.673) < 0.001 淋巴结状态 1.362(0.629~2.949) 0.433 3.541(1.655~7.578) 0.001 肿瘤直径 2.957(1.336~6.546) 0.007 1.980(0.947~4.138) 0.069 癌旁正常组织P2X7R表达 0.954(0.630~1.445) 0.824 1.053(0.713~1.555) 0.796 NSCLC组织CD8+ TILs密度 3.616(1.546~8.459) 0.003 5.199(2.136~12.656) < 0.001 NSCLC组织P2X7R表达 15.048(5.258~43.069) < 0.001 7.737(3.403~17.590) < 0.001 联合化疗 1.046(0.470~2.328) 0.913 0.574(0.232~1.424) 0.231 NSCLC: 非小细胞肺癌; P2X7R: 2型嘌呤能受体家族嘌呤能离子通道型7受体; TILs: 肿瘤浸润性淋巴细胞。
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表 3 多因素分析NSCLC患者预后不良的影响因素
变量 无病生存 总生存 OR(95%CI) P OR(95%CI) P 吸烟史 — — 0.342(0.128~0.915) 0.033 TNM分期 — — 2.999(1.308~6.878) 0.010 淋巴结状态 — — 1.564(0.505~4.844) 0.438 肿瘤直径 2.242(0.890~5.644) 0.087 — — NSCLC组织CD8+ TILs密度 0.893(0.309~2.581) 0.893 2.246(0.647~7.800) 0.203 NSCLC组织P2X7R表达 14.486(4.350~48.241) < 0.001 3.094(1.065~8.987) 0.038 NSCLC: 非小细胞肺癌; P2X7R: 2型嘌呤能受体家族嘌呤能离子通道型7受体; TILs: 肿瘤浸润性淋巴细胞。
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