血清 S100 钙结合蛋白 A4 作为肺癌手术后间质性肺炎急性加重的新型预测标志物。
Serum S100 calcium-binding protein A4 as a novel predictive marker of acute exacerbation of interstitial pneumonia after surgery for lung cancer.
机构信息
Department of Surgical Oncology, Hiroshima University, 1-2-3, Kasumi, Hiroshima, 734-8551, Japan.
Department of Pathology, Hiroshima University, 1-2-3, Kasumi, Hiroshima, 734-8551, Japan.
出版信息
BMC Pulm Med. 2021 Jun 2;21(1):186. doi: 10.1186/s12890-021-01554-y.
BACKGROUND
Acute exacerbation (AE) of interstitial pneumonia (IP) is the most fatal complication after lung resection for lung cancer. To improve the prognosis of lung cancer with IP, the risk factors of AE of IP after lung resection should be assessed. S100 calcium-binding protein A4 (S100A4) is a member of the S100 family of proteins and is a known marker of tissue fibrosis. We examined the usefulness of S100A4 in predicting AE of IP after lung resection for lung cancer.
METHODS
This study included 162 patients with IP findings on preoperative high-resolution computed tomography scan who underwent curative-intent lung resection for primary lung cancer between April 2007 and March 2019. Serum samples were collected preoperatively. Resected lung tissue from 76 patients exhibited usual IP (UIP) pattern in resected lung were performed immunohistochemistry (IHC). Relationship between S100A4 and the incidence of AE of IP and short-term mortality was analyzed.
RESULTS
The receiver operating characteristic area under the curve for serum S100A4 to predict postoperative AE of IP was 0.871 (95% confidence interval [CI], 0.799-0.943; P < 0.001), with a sensitivity of 93.8% and a specificity of 75.3% at the cutoff value of 17.13 ng/mL. Multivariable analysis revealed that a high serum S100A4 level (> 17.13 ng/mL) was a significant risk factor for AE of IP (odds ratio, 42.28; 95% CI, 3.98-449.29; P = 0.002). A 1-year overall survival (OS) was significantly shorter in patients with high serum levels of S100A4 (75.3%) than in those with low serum levels (92.3%; P = 0.003). IHC staining revealed that fibroblasts, lymphocytes, and macrophages expressed S100A4 in the UIP area, and the stroma and fibrosis in the primary tumor expressed S100A4, whereas tumor cells did not.
CONCLUSIONS
Serum S100A4 had a high predictive value for postoperative AE of IP and short-term mortality after lung resection.
背景
间质性肺炎（IP）急性加重（AE）是肺癌肺切除术后最致命的并发症。为改善 IP 合并肺癌患者的预后，应评估肺切除术后 IP AE 的危险因素。S100 钙结合蛋白 A4（S100A4）是 S100 蛋白家族的成员，是组织纤维化的已知标志物。我们检测了 S100A4 在预测肺癌肺切除术后 IP AE 中的作用。
方法
本研究纳入了 2007 年 4 月至 2019 年 3 月间因原发性肺癌接受根治性肺切除术且术前高分辨率 CT 扫描显示有 IP 表现的 162 例患者。采集术前血清样本。对 76 例切除肺组织显示 UIP 模式的患者进行免疫组织化学（IHC）染色。分析 S100A4 与 IP AE 发生率和短期死亡率的关系。
结果
血清 S100A4 预测术后 IP AE 的受试者工作特征曲线下面积为 0.871（95%CI，0.799-0.943；P<0.001），截断值为 17.13ng/ml 时，其灵敏度为 93.8%，特异度为 75.3%。多变量分析显示，高血清 S100A4 水平（>17.13ng/ml）是 IP AE 的显著危险因素（比值比，42.28；95%CI，3.98-449.29；P=0.002）。高血清 S100A4 水平患者 1 年总生存率（OS）明显短于低血清 S100A4 水平患者（75.3% vs. 92.3%；P=0.003）。IHC 染色显示 UIP 区域的成纤维细胞、淋巴细胞和巨噬细胞表达 S100A4，而原发肿瘤的基质和纤维化表达 S100A4，而肿瘤细胞不表达。
结论
血清 S100A4 对肺切除术后 IP AE 和短期死亡率具有较高的预测价值。
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