Li Yan, Miao Li-Yun, Xiao Yong-Long, Cai Hou-Rong, Zhang De-Ping
Department of Respiratory Medicine, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China E-mail :
Asian Pac J Cancer Prev. 2014;15(1):139-43. doi: 10.7314/apjcp.2014.15.1.139.
Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration . Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets (81.7±0.45% vs 41.0±3.50%, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, 4.33±0.33 vs 0.33±0.33, P=0.01; in SPC-A1, 2.67±0.33 vs 0.00±0.00, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (>200x109/L, 3 months versus ≤200x109/L, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.
尽管血小板与肺癌之间的相关性已得到认可,但血小板对非小细胞肺癌(NSCLC)转移的影响仍有待详细确定。在本研究中,伤口愈合试验揭示了血小板在NSCLC细胞迁移中的作用。因此,肺腺癌A549细胞与血小板共培养后的平均迁移率显著升高(81.7±0.45%对41.0±3.50%,P<0.01)。通过逆转录-聚合酶链反应检测甘油醛-3-磷酸脱氢酶(GAPDH)的表达,以研究血小板对NSCLC细胞增殖的影响。结果显示,A549和SPC-A1细胞的增殖未受影响。通过将A549细胞和SPC-A1细胞注入小鼠侧尾静脉建立小鼠模型。我们发现,与血小板共输注后,肺内肿瘤转移结节显著增加(A549组,4.33±0.33对0.33±0.33,P=0.01;SPC-A1组,2.67±0.33对0.00±0.00,P=0.01)。此外,对2009年1月至2011年12月期间连续收治的新诊断为NSCLC(TNM分期III或IV期)且无法手术的患者进行回顾性分析。采用Kaplan-Meier法,血小板计数高的NSCLC患者的无进展生存期明显短于血小板计数低的患者(>200×10⁹/L,3个月对≤200×10⁹/L,5个月,P=0.001)。通过Cox回归分析,血小板计数升高也被确定为无进展生存期的独立预后因素(校正风险比:1.69;95%可信区间:1.16,2.46;P=0.006)。本研究表明,血小板可能通过促进癌细胞迁移而有助于血行转移过程,最终影响NSCLC的预后。