Viswam S Nair1, Olivier Gevaert2, Guido Davidzon3, Sylvia K Plevritis2, Robert West4. 1. Division of Pulmonary & Critical Care Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, United States. Electronic address: viswamnair@stanford.edu. 2. Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, United States. 3. Department of Radiology, Division of Nuclear Medicine, Loyola University Chicago, Stritch School of Medicine, 2160 S, 1st Avenue, Maywood, IL 60153, United States. 4. Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, United States.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
INTRODUCTION: 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 NSCLCpatients. METHODS: We examined NF-κBp65 by immunohistochemistry (IHC) using a Tissue Microarray. Staining intensity was assessed by qualitative ordinal scoring and compared to tumorFDG 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: J Whelan; P Ghersa; R Hooft van Huijsduijnen; J Gray; G Chandra; F Talabot; J F DeLamarter Journal: Nucleic Acids Res Date: 1991-05-25 Impact factor: 16.971
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Authors: Weiruo Zhang; Gina Bouchard; Alice Yu; Majid Shafiq; Mehran Jamali; Joseph B Shrager; Kelsey Ayers; Shaimaa Bakr; Andrew J Gentles; Maximilian Diehn; Andrew Quon; Robert B West; Viswam Nair; Matt van de Rijn; Sandy Napel; Sylvia K Plevritis Journal: Cancer Res Date: 2018-05-14 Impact factor: 12.701