Lung cancer remains the most common cancer worldwide, with a limited prognosis despite personalized treatment regimens. Low-dose computed tomography (CT) scanning as a means of early diagnosis has been disappointing due to the high false positive rate. Other non-invasive means of testing need to be developed that offer both timely diagnosis and predict prognosis.Methods: In the course of stool testing in large-scale testing of 2922 patients at increased risk of CRC, we were able to ascertain 112 patients documented to have prospectively been diagnosed with lung cancer. Stool and colonic effluents were tested for p87 with anti-adenoma antibody (Adnab-9) reactivity by ELISA and Western blot. Survival data were obtained where available.Results: Of 112 cancers, approximately 27.6% were squamous (SSC), 17.9% were adenocarcinoma, 8% were small, 6.25% were large cell, 3.57% were designated non-small cell cancer (NSCLC), 0.89% were indeterminate, 0.89% were lepidic spread, 3.57% had metastasis, and in 31.25%, data were unavailable. In total, 49.1% of the lung cancer patients had fecal Adnab-9 testing. Overall, 60% had positive testing compared to 38%, which was significant (OR2.19 [1.06–4.53];p= 0.045). Cancers with higher lethality were less likely to test positive (approximately 8.5% each for both small and large cell lung cancers) and higher, with 56% for SCC and 25% for adenocarcinoma (0% NSCLC). In the larger groups, overall survival was worse in those testing positive: 474 testing positives versus 844 days in SCC and 54 testing positive versus 749 days in adenocarcinoma patients. Most importantly, the time from a positive test to the clinical diagnosis ranged from 2.72 years for small cell, 3.13 for adenocarcinoma, 5.07 for NSCLC, 6.07 for SSC, and 6.24 for large cell cancer. In excluded cases where cancer in the lung was believed to be metastatic, 83.3% of cancers were positive.Conclusions: At a projected real-world sensitivity of 0.60 and specificity of 0.60, and the ability to predate diagnosis by up to 4.7 years overall, this test could help direct lung cancer screening. In addition, the Adnab-9 testing selectively detects worse tumor types (87.5%) and those with worse prognoses amongst the more common, favorable phenotypes, thus making early diagnosis possible in those patients who stand to benefit most from this strategy. Metastatic lung cancer, also detected by the test, should be identified by the follow-up imaging studies and, therefore, would not be considered to be a major pitfall.
肺癌仍是全球最常见的恶性肿瘤,尽管已有个体化治疗方案,其预后改善仍有限。低剂量计算机断层扫描(CT)作为早期诊断手段因假阳性率高而效果不尽如人意。亟需开发其他无创检测方法,既能实现及时诊断,又能预测预后。 方法:在对2922例结直肠癌高危患者进行大规模粪便检测过程中,我们确认了112例前瞻性诊断为肺癌的患者。通过酶联免疫吸附试验和蛋白质印迹法检测粪便及结肠流出物中p87蛋白的抗腺瘤抗体(Adnab-9)反应性。在可获得数据的情况下收集生存资料。 结果:在112例肺癌中,约27.6%为鳞状细胞癌(SSC),17.9%为腺癌,8%为小细胞癌,6.25%为大细胞癌,3.57%被归类为非小细胞肺癌(NSCLC),0.89%为未确定类型,0.89%为鳞屑样生长型,3.57%存在转移,31.25%数据缺失。总体而言,49.1%的肺癌患者接受了粪便Adnab-9检测。检测阳性率为60%,显著高于对照组的38%(比值比2.19[1.06–4.53];p=0.045)。致死率较高的肺癌类型检测阳性率较低(小细胞肺癌和大细胞肺癌各约8.5%),而鳞癌阳性率达56%,腺癌为25%(非小细胞肺癌为0%)。在较大样本组中,检测阳性者的总生存期更差:鳞癌阳性组474天vs阴性组844天;腺癌阳性组54天vs阴性组749天。最重要的是,从检测阳性到临床确诊的时间间隔分别为:小细胞癌2.72年、腺癌3.13年、非小细胞肺癌5.07年、鳞癌6.07年、大细胞癌6.24年。在排除的疑似肺转移癌病例中,83.3%呈阳性反应。 结论:该检测在真实世界中的敏感性和特异性预计均为0.60,且平均可提前4.7年预警诊断,有助于指导肺癌筛查。此外,Adnab-9检测能选择性识别恶性程度更高的肿瘤类型(87.5%),并在常见良好表型中筛选出预后较差者,从而为最能从此策略中获益的患者实现早期诊断。该检测虽也能检出转移性肺癌,但可通过后续影像学检查加以鉴别,因此不构成主要缺陷。
Historic p87 Is Diagnostic for Lung Cancer Preceding Clinical Presentation by at Least 4 Years