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Purpose: Epidermal growth factor receptor (EGFR) mutation is the most common target for precision treatment in metastatic lung adenocarcinoma. We investigated the predictive role of 18F-FDG PET/CT and clinicopathological features for EGFR mutations in lung adenocarcinoma with bone metastasis. Methods: Seventy-five lung adenocarcinoma patients with histologically confirmed bone metastasis were included. They all received EGFR status test and PET/CT before systemic treatment. The differences of maximum standardized uptake value (SUVmax) in primary tumor (pSUVmax), regional lymph node (nSUVmax) and bone metastasis (bmSUVmax) between different EGFR status groups were compared, alongside with common clinicopathological features. Multivariate logistic regression analysis was performed to evaluate predictors of EGFR mutations. Results: EGFR mutations were found in 37 patients (49.3%). EGFR mutations were more common in females, non-smokers, expression of Thyroid Transcription Factor-1 (TTF-1) and NaspinA. Low bmSUVmax was significantly associated with EGFR mutations, while no significant difference was observed in pSUVmax and nSUVmax. Multivariate analysis showed that bmSUVmax ≤7, non-smoking, expression of TTF-1 were predictors of EGFR mutations. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was 0.84 for the combination of the three factors. Conclusion: Low bmSUVmax is more frequently in EGFR mutations, and bmSUVmax is an independent predictor of EGFR mutations. Combining bmSUVmax with other clinicopathological features could forecast the EGFR status in lung adenocarcinoma with unavailable EGFR gene testing.

Purpose: We evaluated the imaging and clinical features for discriminating the possibility of metastasis among FDG-avid bone lesions in 18F-FDG PET/CT in patients who have received bone biopsy. Methods: The retrospective study included patients who underwent both 18F-FDG PET/CT and bone biopsy for FDG-avid bone lesions. Bone lesions maximum standardized uptake value (SUVmax), CT findings, alongside with common clinical features were analyzed. Results: From the 338 patients enrolled in the final study, all of them were received bone biopsy. Biopsies confirm metastasis in 256 cases (75.74%) and benign tissue in 82 cases (24.26%). Metastasis group had higher bone SUVmax than benign group (median 7.9 vs 4.5, p

Despite recent advances in targeted and immune‐based therapies, the poor prognosis of lung adenocarcinoma (LUAD) with bone metastasis (BM) remains a challenge. First, two‐dimensional gel electrophoresis (2‐DE) was used to identify proteins that were differentially expressed in LUAD with BM, and then matrix‐assisted laser desorption/ionization time of flight mass spectrometry (MALDI‐TOF‐MS) was used to identify these proteins. Second, the Cancer Genome Atlas (TCGA) was used to identify mutations in these differentially expressed proteins and Kaplan–Meier plotter (KM Plotter) was used to generate survival curves for the analyzed cases. Immunohistochemistry (IHC) was used to check the expression of proteins in 28 patients with BM and nine patients with LUAD. Lastly, the results were analyzed with respect to clinical features and patient's follow‐up. We identified a number of matched proteins from 2‐DE. High expression of enolase 1 (ENO1) (HR = 1.67, logrank P = 1.9E‐05), ribosomal protein lateral stalk subunit P2 (RPLP2) (HR = 1.77, logrank P = 2.9e‐06), and NME/NM23 nucleoside diphosphate kinase 2 (NME1‐NME2) (HR = 2.65, logrank P = 3.9E‐15) was all significantly associated with poor survival (P

Introduction: Despite recent advances in targeted and immune-based therapies, the poor prognosis of lung adenocarcinoma (LUAD) with bone metastasis (BM) remains a challenge. Here, we aimed to investigate the potential biomarker for LUAD with BM. Methods: First, we collected 5 patients with traumatic amputation, 5 patients with bone infiltration, 9 LUAD patients who underwent curative resection or thoracoscopic lobectomy and 32 LUAD patients with BM who underwent bone biopsy in the Shanghai Sixth People's Hospital (China) from May 2014 to January 2017. 28 bone biopsy samples and 9 LUAD samples were used for immunohistochemistry assays (IHC) and OS (follow-up period of more than one year). Secondly, RT-PCR, IHC, and Western blotting (WB) were used to assess Aldehyde Dehydrogenase 2 (ALDH2) RNA and protein expression levels in samples of LUAD with BM. The Cancer Genome Atlas (TCGA) and Kaplan Meier plotter (KM Plotter) were used to generate survival curves. Thirdly, we analyzed the methylation associated genes and found DNA Methyltransferase 1 (DNMT1) and methyl-CpG binding domain 4 (MBD4) down-regulated the expression of ALDH2. Fourthly, we explored the impact of ALDH2 on tumor cell function and apoptosis via cell counting kit-8 (CCK8), Transwell and Fluorescence activated cell sorter (FACS). Then, we demonstrated that ALDH2 might affect mitogen-activated protein kinase (MAPK) and Epithelial-mesenchymal transition (EMT) markers through WB assays. Last, to confirm ALDH2 effect in vivo, we injected PLVX-flag-aldh2 and PLVX-flag H1299 cells into the left cardiac ventricle to check the effect of ALDH2 in BM and calculated the overall survival of mice. Results: We identified both mRNA and protein levels of ALDH2 were much lower in tumor tissues than in normal tissues, and they were even lower in tissues that exhibited increased migratory capacity. This low expression feature may be attributed to DNA methylation of ALDH2.The result of over expressing or knocking down ALDH2 showed that this gene inhibited proliferation, migration and promoted apoptosis both in vivo and in vitro. Overexpression of ALDH2 can inhibit MAPK signaling pathway and EMT in H1299. It also inhibited the occurrence of BM in LUAD and expanded survival in mice (p=0.003). Conclusions: This is the first time that instance where ALDH2 was associated with disease severity and progression in LUAD patients with BM. Thus, with this study, we have identified potential biomarkers and therapeutic targets for this disease. Supported by the National Natural Science Foundation of China (grant No. 81672852,81602519), a three year action plan to promote clinical skills and clinical innovation in municipal hospitals (20164Y0099), Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (20172024). Citation Format: Mengdi Yang, Guangyu Yao, Zhiyu Wang, Jing Sun, Yiyi Zhou, Yifeng Gu, Hui Zhao. The differential expression of ALDH2 is correlated with prognosis of lungadenocarcinoma with bone metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-319.

e20534 Background: The prognosis of lung adenocarcinoma (LUAD) with bone metastases (BM) is still poor. It is increasingly demanded to find key proteins to solve the problem. Methods: First, we collected three groups of bone tissues: normal, osteosarcoma, and LUAD with BM from Shanghai Sixth People's Hospital. Each group had five patients. Two-dimensional gel electrophoresis (2D-E) was used to find proteins with significant differences, then Maldi-tof-tof mass spectrometry was used to identify the proteins. Second, immunohistochemical (IHC) was used to check the expression of proteins in 28 BM patients and 9 LUAD patients. Real-Time PCR (QPCR), western boltting (WB) were further used to check the expression of para-LUAD, LUAD and BM. Last, we downloaded RNA-seq and clinical datas from the Cancer Genome Atlas(TCGA) database to further verify differentially expressed genes using ‘DESeq’ package and explored their relationship with survival using ‘survival’ package in R. Kaplan-Meier survival plot and the hazard ratio and logrankp was calculated (www.kmplot.com/lung). Results: We got 26 matched proteins from 2D-E, then selected Aldehyde Dehydrogenase 2 Family (Mitochondrial) (ALDH2) and Enolase-1 (ENO1). In IHC analysis, strong-stained ALDH2 showed OR = 0.568 (95 % confidence interval [CI], 0.317-1.019), p= 0.036, strong-stained ENO1 OR = 1.929 (95% CI, 0.915-4.066), p= 0.023, were associated with bone metastastic incidences in LUAD with statistically significantly difference. QPCR, WB validated that ALDH2 had lowest expression in BM, followed by LUAD samples, and para-LUAD highest. However, ENO1 displayed the opposite tendency . In TCGA LUAD RNA-seq, ALDH2 had low expression ( p= 3.83E-12, log2Foldchange = 1.158), and ENO1 was up-regulated ( p= 0.0004, log2Foldchange = 1.210 ). ALDH2 is correlated with better survival (HR = 0.47, 95% CI (0.37-0.61), logrankP = 6.5E-10), while ENO1 was inversely associated with better prognosis (HR = 1.67,95% CI (1.32-2.12), logrankP = 1.9E-05) in K-M Plotter. Conclusions: In this study, we discovered new differential expression and prognosis related proteins, ALDH2 and ENO1, and they are worthy of further exploration into the underlying mechanism.