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Background The genomic profile of non-small cell lung cancer (NSCLC) in Asians is distinct from that of Caucasians, but comprehensive genetic profiling reports have been limited for Asian patients. We aimed to elucidate genomic characteristics of Chinese NSCLC patients and develop potential model including genomic characteristics to predict postoperative prognosis. Methods Resected tumor samples from 511 patients with stage I-IV lung cancer were subjected to targeted sequencing using a panel of 295 cancer-related genes. Based on the molecular profiles and clinical features, we established nomogram models with predictors consisting of integrated clinical and genomic characteristics to provide post-operative risk stratification. Results Compared to the TCGA population (mainly Caucasians), there was a significantly higher frequency of EGFR (53.7% vs. 14.4%) and NOTCH3 (8.4% vs. 1.3%) mutations and less mutated KRAS (11.0% vs. 32.6%), KEAP1 (4.4% vs. 17.4%) and LRP1B (16.3% vs. 29.6%) in Chinese lung adenocarcinomas (LUAD). Distinct patterns of mutually exclusive and co-occurring mutations were identified between LUAD and lung squamous cell carcinoma (LUSC), indicating the unique histology-specific tumorigenesis mechanism of each subtype. We observed alterations in pathways correlated with clinical characteristics. Additionally, we constructed nomogram model with predictors consisting of clinical and genomic characteristics, which were more accurate than models with clinical characteristics or TNM staging only both in stage I-IIIA patients and T1-2N0M0 sub-cohort. Conclusions This study revealed Chinese NSCLC patients have unique genomic profile. Furthermore, the nomogram model combining clinical features with genomic characteristics could improve risk stratification in early-stage NSCLC.

Lu Yang,1,* Chong Pang,2,* Fei Xu,1 Guangjian Yang,1 Haiyan Xu,3 Changli Wang,2 Yan Wang1 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Lung Cancer Center, Tianjin, 300060, People’s Republic of China; 3Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan WangDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of ChinaTel +86 139 1179 3771Fax +86 106773 4107Email wangyanyifu@163.comChangli WangDepartment of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Lung Cancer Center, Tianjin 300060, People’s Republic of ChinaEmail wangchangli@tjmuch.comBackground: Nearly 30% of stage IA non-small-cell lung cancer patients eventually die of recurrence or metastasis. This study aimed to predict stage IA lung adenocarcinoma (LADC) patients who underwent radical resection with a high risk of recurrence or metastasis.Methods: Information on clinicopathological, genetic and therapeutic features and recurrence status was collected in this retrospective and two-center study. A nomogram based on multivariate analysis was established to predict disease-free survival. Further stratification was performed to identify populations with a high risk of relapse.Results: A total of 1584 patients with pathological stage IA LADC who underwent radical surgery between 2011 and 2015 were enrolled from two medical institutions in this study. The nomogram including tumor differentiation and EGFR mutation had a higher C-index of 0.880 (95% CI 0.833– 0.926) compared to 0.598 (95% CI 0.486– 0.711) for the AJCC 8th TNM staging system. Furthermore, the C-index for the validation cohort was 0.798 (95% CI 0.738– 0.857). In addition, the 3-year cumulative nonrecurrence rate in the high-risk group stratified by this model was 21.8% compared to 98.1% in the low-risk group.Conclusion: This study proposed a new nomogram including tumor differentiation and EGFR mutation to predict recurrence or metastatic probability in stage IA LADC patients who underwent radical surgery. This nomogram could identify patients in the high-risk group and help guide adjuvant treatment in the future.Keywords: nomogram, stage IA, lung adenocarcinoma, disease-free survival

Metal silicides are used to reduce the polycrystalline silicon (polysilicon) gate and contact resistances during fabrication of transistors in microelectronics devices. Generally, Titanium disilicides and Cobalt disilicides are widely utilized on transistors while Nickel monosilicides (NiSi) are still under intense investigation for future transistor technology. However, reactions between parent metals (Ti, Co and Ni) and silicon often present many different problems during silicides formation. DOCTOR OF PHILOSOPHY (SME)