Division of Pulmonary & Critical Care Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, United States.
Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, United States.
Lung Cancer. 2014 Feb;83(2):189-96. doi: 10.1016/j.lungcan.2013.11.001. Epub 2013 Nov 13.
We previously demonstrated that NF-κB may be associated with (18)F-FDG PET uptake and patient prognosis using radiogenomics in patients with non-small cell lung cancer (NSCLC). To validate these results, we assessed NF-κB protein expression in an extended cohort of NSCLC patients.
We examined NF-κBp65 by immunohistochemistry (IHC) using a Tissue Microarray. Staining intensity was assessed by qualitative ordinal scoring and compared to tumor FDG uptake (SUVmax and SUVmean), lactate dehydrogenase A (LDHA) expression (as a positive control) and outcome using ANOVA, Kaplan Meier (KM), and Cox-proportional hazards (CPH) analysis.
365 tumors from 355 patients with long-term follow-up were analyzed. The average age for patients was 67±11 years, 46% were male and 67% were ever smokers. Stage I and II patients comprised 83% of the cohort and the majority had adenocarcinoma (73%). From 88 FDG PET scans available, average SUVmax and SUVmean were 8.3±6.6, and 3.7±2.4 respectively. Increasing NF-κBp65 expression, but not LDHA expression, was associated with higher SUVmax and SUVmean (p=0.03 and 0.02 respectively). Both NF-κBp65 and positive FDG uptake were significantly associated with more advanced stage, tumor histology and invasion. Higher NF-κBp65 expression was associated with death by KM analysis (p=0.06) while LDHA was strongly associated with recurrence (p=0.04). Increased levels of combined NF-κBp65 and LDHA expression were synergistic and associated with both recurrence (p=0.04) and death (p=0.03).
NF-κB IHC was a modest biomarker of prognosis that associated with tumor glucose metabolism on FDG PET when compared to existing molecular correlates like LDHA, which was synergistic with NF-κB for outcome. These findings recapitulate radiogenomics profiles previously reported by our group and provide a methodology for studying tumor biology using computational approaches.
我们之前通过非小细胞肺癌（NSCLC）的放射组学研究表明，NF-κB 可能与（18）F-FDG PET 摄取和患者预后相关。为了验证这些结果，我们在一个更大的 NSCLC 患者队列中评估了 NF-κB 蛋白表达。
我们使用组织微阵列通过免疫组织化学（IHC）检查 NF-κBp65。通过定性ordinal 评分评估染色强度，并与肿瘤 FDG 摄取（SUVmax 和 SUVmean）、乳酸脱氢酶 A（LDHA）表达（作为阳性对照）以及使用 ANOVA、Kaplan-Meier（KM）和 Cox 比例风险（CPH）分析进行比较。
分析了 355 名患者的 365 个肿瘤，这些患者具有长期随访结果。患者的平均年龄为 67±11 岁，46%为男性，67%为曾经吸烟者。Ⅰ期和Ⅱ期患者占队列的 83%，大多数为腺癌（73%）。在 88 个 FDG PET 扫描中，平均 SUVmax 和 SUVmean 分别为 8.3±6.6 和 3.7±2.4。NF-κBp65 表达的增加，但不是 LDHA 表达的增加，与 SUVmax 和 SUVmean 更高相关（分别为 p=0.03 和 0.02）。NF-κBp65 和阳性 FDG 摄取均与更晚期的肿瘤分期、肿瘤组织学和侵袭有关。KM 分析表明，NF-κBp65 表达较高与死亡相关（p=0.06），而 LDHA 与复发强烈相关（p=0.04）。NF-κBp65 和 LDHA 表达水平升高具有协同作用，与复发（p=0.04）和死亡（p=0.03）均相关。
与现有的分子标志物 LDHA 相比，NF-κB IHC 是一种适度的预后生物标志物，与 FDG PET 上的肿瘤葡萄糖代谢相关，而 NF-κB 与 LDHA 联合用于预测结果具有协同作用。这些发现重现了我们小组之前报道的放射组学谱，并为使用计算方法研究肿瘤生物学提供了一种方法。
