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e14574 Background: Immune checkpoint inhibitors (ICIs), targeting the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1) or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) have demonstrated impressive anti-tumor efficacy in multiple tumors, particularly non-small cell lung cancer (NSCLC). However, only a minority of patients could clinically benefit from the ICIs. Therefore, it is of vital clinical significance to explore underlying predictive biomarkers to identify to identify these most potentially ICIs-benefitable patients. Nuclear pore associated protein 1 ( NPAP1) encodes an protein is associated with the nuclear pore complex and has been previously reported as a potential prognostic biomarker for laryngeal, colorectal and lung cancers. However, its role in lung cancer immunotherapy remains unknown. Here we aimed to explore the association between NPAP1 and ICIs. Methods: 165 NSCLC patients from three public immunotherapy cohorts (Hellmann 2018, Miao 2018, and Rizvi 2015 cohort) were included to analyze the association between NPAP1 gene mutation and efficacy of ICI therapy. Genomic, survival and mRNA data of NSCLC patients from the Cancer Genome Atlas (TCGA) database was used to explore the potential mechanisms of anti-tumor immunity. Results: NSCLC patients with NPAP1 mutation were significantly associated with better PFS (HR = 0.37; 95% CI, 0.19-0.71; P = 0.002), objective response rate (ORR, 54.2% vs 28.4%; P = 0.048) and durable clinical benefit (DCB, 75.0% vs 42.6%; P= 0.003) after ICIs therapy, compared with those with wide-type NPAP1. NPAP1 mutation were associated with increased TMB ( P < 0.001). In the multivariable Cox proportional hazards regression model adjusted by smoking status, PD-L1 expression and TMB, the association between NPAP1 mutation and PFS remained significant (HR = 0.46; 95% CI, 0.23-0.92; P = 0.028). In contrast, no association between NPAP1 mutation and OS (LUAD: P = 0.24 ; LUSC: P = 0.94) or PFS (LUAD: P = 0.3; LUSC: P = 0.72) was observed in TCGA datasets, suggesting that NPAP1 mutation may be a predictive but not a prognostic factor in ICI treatment for NSCLC patients. Based on CIBERSORT-inferred tumor infiltrating lymphocytes from TCGA, NPAP1 mutation was significantly associated with higher activated memory CD4+ T cell and CD8+ T cell. Moreover, NPAP1 mutation was associated with increased TMB ( P < 0.001) and neoantigen load ( P < 0.001) in TCGA. Conclusions: Our results demonstrated that NPAP1 mutation is an underlying classifier that could stratify patients with NSCLC for ICIs. The role of NPAP1 in immunotherapy is needed to be further studied.

The purpose was to investigate the efficacy and safety of Osimertinib in the treatment of advanced non-small cell lung cancer and to analyze its effects on the expression of serum matrix metalloproteinase-7 (MMP-7) and matrix metallo-proteinase-9 (MMP-9). Eighty patients were equally divided into observation and control group. The observation group was given Osimertinib combined with conventional chemotherapy and the other was treated with conventional chemotherapy alone. The short-term efficacy, the levels of serum MMP-7, MMP-9 and adverse reactions were compared. The effectiveness and clinical benefit rate of the observation group were 62.50% and 92.50% respectively, significantly higher than the control group. There was no significant difference in MMP-7 and MMP-9 before treatment however there was a significant difference after treatment, and the serum MMP-7MMP-9 levels showed a trend of increasing with decreasing efficacy. After treatment, comparing with control group, serum MMP-7 and MMP-9 levels were significantly lower, the Karnofsky score was significantly higher, and the improvement effect of the quality of life was statistically significant. Besides, the incidence of leukopenia, thrombocytopenia, anemia and gastrointestinal symptoms were significantly lower. In the treatment of patients with advanced non-small cell lung cancer, Osimertinib significantly reduced the expression of serum MMP-7, MMP-9, improved the clinical benefit and quality of life of patients. The clinical efficacy was significant with a high safety.

Objective To determine the prognostic value of red cell distribution width (RDW) and circulating tumor cells with epithelial-mesenchymal transition phenotype (M-CTC) in lung adenocarcinoma (LUAD). Patients and methods Clinical and laboratory data of 60 patients with LUAD were collected. CTCs were isolated from their peripheral blood using the CanPatrolTM CTC enrichment method. The indicators of RDW and neutrophil lymphocyte ratio (NLR) were calculated based on the laboratory standards. Results A total of 60 LUAD patients were enrolled, of which 19 (31.7%) had high RDW (>0.14) and 32 (53.3%) were positive for M-CTCs. There was no significant correlation between RDW and the clinical characteristics. M-CTC was not significantly associated with tumor size and differentiation, age, gender, tumor stage, and histological type but correlated significantly with lymphatic metastasis (P = 0.044), high NLR (>2.26, P = 0.023), and high RDW (>0.14, P = 0.036). Furthermore, the M-CTC+ LUAD patients had a significantly poor recurrence-free survival (RFS; Log rank P =0.001, HR = 2.749, 95% CI = 1.489-5.078) and overall survival (OS; Log rank P =0.022, HR = 2.283, 95% CI = 1.128-4.622) compared to the M-CTC- patients. Similarly, high RDW also correlated with worse RFS (Log rank P = 0.008, HR = 2.331, 95% CI = 1.248-4.353) and OS (Log rank P = 0.004, HR = 0.004, 95% CI = 1.398-5.525). Conclusion M-CTC is significantly related to RDW and NLR, and an independent prognostic factor in LUAD.

Circulating tumor cells (CTCs) are a heterogeneous population of tumor cells with distinct clinical and biological properties. The aim of the present study was to evaluate the relationship between CTCs with the epithelial-mesenchymal transition phenotype (CTC EMT) and the proliferative marker Ki67, and their prognostic value in non-small cell lung cancer (NSCLC). CTCs were isolated from the peripheral blood of 84 NSCLC patients using the CanPatrol(TM) CTC enrichment method, and the expression of Ki67 in tumor tissues were detected by immunohistochemistry. Almost two-thirds (61/84) of the patients were positive for CTC EMT, and 55 (65.4%) patients had high in-situ expression of Ki67 (≥ 14%) in the tumor tissues. CTC EMT was not significantly associated with tumor size and differentiation, age, gender and histological type, but correlated with lymphatic metastasis, tumor stage and Ki67 overexpression. Furthermore, the CTC EMT+ NSCLC patients had a significantly lower recurrence-free survival (RFS) and overall survival (OS) compared to the negative patients. Similarly, Ki67 levels ≥ 14% were associated with a significantly lower RFS and OS. In conclusion, CTC EMT is significantly related to Ki67 expression, and is a risk factor of NSCLC.

Background Microsatellite instability (MSI) has important clinical implications related to therapeutic options and prognostic assessment. Few studies have been done on the frequency of MSI in cancers and the correlation between microsatellite status and clinicopathological features in Chinese solid tumor patients. Methods A total of 10149 Chinese solid tumor patients were collected for genome testing using a targeted next-generation sequencing (NGS) panel (OrigiMed, Shanghai). Microsatellite status and other clinicopathological features were examined. Fisher's exact test was used for statistical analysis. Results MSI-high (MSI-H) was observed in 188 solid tumors (1.8%). Cancer subtypes with significantly higher MSI frequencies included colorectal adenocarcinoma (8.4%), gastric adenocarcinoma (6.9%) and intrahepatic cholangiocarcinoma (2.7%). No statistical significant difference was found in the proportion of MSI in women and men (1.9 % vs 1.7%, respectively). The proportion MSI tumors was higher in older patients (1.3% at 60-69 years, 2.8% at 70-79 years,P Conclusions This study revealed MSI-H in approximately 1.8% of Chinese solid tumor patients and a significant association between MSI-H and MMR gene mutations. These results suggest that there are specific tumor types and clinicopathological features associated with a higher frequency of MSI, indicating a bias during tumorigenesis. Also, these results may potentially contribute to more effective treatment options and a better prognostic assessment for solid tumor patients. Citation Format: Huilin Wang, Jiang Zhu, Guanbiao Liang, Yongyong Wang, Jianji Guo, Min Zheng, Qin Fu, Weiwei Shi. Frequent microsatellite instability in Chinese solid tumor patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4316.

416 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancer in China. The genetic characterizations have already been described in many studies, but the immune microenvironment features were seldom reported. Our study was aimed to explore the relationship between the immune profile in stage IIIa ESCC and patients’ prognosis. Methods: 20 eligible stage IIIa ESCC patients with received surgery and radiotherapy (19 with and 1 without radiotherapy). RNA targeted sequencing was performed on 20 primary tumor specimens. Transcripts of 395 immune-related genes expressed in tumor were analyzed. The univariate and multivariate Cox proportional hazards analyses were examined the relations of 395 genes’ expression and the prognosis. Results: Patients were divided into two groups based on the median expression values of 395 genes. The univariate analyses showed 20 genes were significantly associated with overall survival (OS). Unsupervised hierarchical clustering analysis using 20 gene expression data revealed two distinct clusters (cluster 1 and 2). The cluster1 patients had high level expression of AXL, ADGRE5, CD40, CXCR6, MPO, etc., which were associated with tumor proliferation and migration. However, the cluster2 patients expressed higher NOS2, IL15, IKZF2, TNFRSF18 which were related with T lymphocyte activated. Therefore, the cluster2 patients had significantly longer OS than cluster 1. Moreover, the combined expression of 10 genes (CD40, ADGRE5, CSF1R, CCR1, IGSF6, MPO, MRC1, SRGN, CD63, LRP1) which had high correlation among 20 genes were significantly related to OS and DFS (disease free survival) in univariate analysis. The multivariate analyses demonstrated that 10 genes signature expression was the independent high risk factor for OS, and the low signature value was associated with better prognosis. Conclusions: In IIIa ESCC, the 20 genes can profile the tumor immune microenvironment, and were independently associated with the patients’ OS. The 10 genes’ signature which represents the malignancy and immune activation of tumor was an independent predictive factor for OS, which can identify the patients with favorable or poor prognosis.

Recent studies report a correlation between excision repair cross-complementing group 2 (ERCC2) Lys751Gln polymorphism and an increased risk of lung cancer, but results are controversial and inconclusive. Thus, we conducted a comprehensive meta-analysis in order to assess the correlation between them. Our study uses an odds ratio (OR) with a 95% confidence interval (95% CI) to evaluate the strength of the association; we also performed Begg's funnel plot and the Egger's test to assess the publication bias of previous articles. Finally, our meta-analysis is comprised of 28 full studies, including 23,370 subjects (10,242 cases and 13,128 controls). Our overall research shows that ERCC2 Lys751Gln polymorphism carries an increased risk of developing lung cancer (C vs. A: OR = 1.160, 95% CI = 1.081–1.245, p = .000; CC vs. AA: OR = 1.252, 95% CI = 1.130–1.388, p = .000; CA vs. AA: OR = 1.152, 95% CI = 1.060–1.252, p = .001; CC+CA vs. AA: OR = 1.186, 95% CI = 1.089–1.292, p = .000; CC vs. CA+AA: OR = 1.196, 95% CI = 1.087–1.316, p = .000). In ethnic subgroup analyses, we find a significant risk among Caucasians (C vs. A: OR = 1.106, 95% CI = 1.048–1.166, p = .000; CC vs. AA: OR = 1.233, 95% CI = 1.103–1.378, p = .000; CC+CA vs. AA: OR = 1.113, 95% CI = 1.033–1.199, p = .005; CC vs. CA+AA: OR = 1.185, 95% CI = 1.069–1.313, p = .001) and among Asians under two genetic models (CA vs. AA: OR = 1.265, 95% CI = 1.034–1.549, p = .023; CC+CA vs. AA: OR = 1.252, 95% CI = 1.015–1.544, p = .036). These results were confirmed by similar findings, demonstrated by stratified analyses in study design and histological typing. This meta-analysis indicates that ERCC2 Lys751Gln polymorphism may lead to an increased susceptibility to lung cancer risk among Caucasians and Asians.

The association between the microsomal epoxide hydrolase 1 gene (EPHX1) Tyr113His polymorphism and lung cancer and breast cancer risk has been reported in many recent studies, but there is no consensus among the results. Thus, we examined the association between the EPHX1 Tyr113His polymorphism and lung cancer through a meta-analysis. A comprehensive literature search was performed using the Pubmed and Embase databases. Odds ratios with 95% confidence intervals were used to assess the strength of associations. Our meta-analysis suggested that the Tyr113His polymorphism was associated with lung cancer risk in Asians under 3 genetic models, including a C vs T, CC vs TT, and recessive model. However, the risk was decreased in Caucasians under the genetic models, including a C vs T, CC vs TT, or CT vs TT, dominant, and recessive model. In contrast, there was no association with breast cancer risk for any of the genetic models. Our meta-analysis suggested that the EPHX1 Tyr113His polymorphism may be a risk factor for lung cancer in Asians, whereas it may be a decreased risk factor among Caucasians. However, this polymorphism was not found to be associated with breast cancer.

Background: Characterization of genomic alterations that drive patient disease development is critical in cancer management. The genomic alteration and population characteristics between the primary tumors and metastases in patients with non-small cell lung cancer (NSCLC) is still unclear. Here we evaluated the frequency and distribution of all classes of genomic alterations in both primary and metastatic NSCLC by comprehensive genomic profiling approach. Methods: FFPE tumor and matched blood samples of 1135 Chinese NSCLC patients (female:male is 670: 465), including 954 primary tumors and 181 metastases, were collected for next-generation sequencing (NGS) based panel assay. Gene copy number variations (CNV) including gene amplifications and deletions, short variants, and gene fusions were assessed. Results: On average, 0.65 gene copy number variations were detected in the 181 metastatic lesions, which is higher than 0.43 CNVs per sample in the primary lesions (p value is 0.003). No significant difference was found in short variants (2.48 vs 2.31), fusions (0.27 vs 0.20) and germline mutations (0.26 vs 0.31) between the primary and metastatic NSCLC. In the top-ranked genes with copy number alterations, EGFR amplifications were detected in 11% of the primary and 15% in metastases. MET amplifications, CDKN2A/B deletions, and PMS2 deletions were more frequently found in metastatic lesions: MET (7.7% vs 1.7%, p=0.0001), CDKN2A (5.5% vs 1.5%, p=0.002), CDKN2B (5.0% vs 1.9%, p=0.0007), and PMS2 (3.9% vs 1.2%, p=0.016). Conclusions: Copy number variations are common driver mutations in NSCLC. We reported here that the prevalence of copy number variations between primary and metastatic lung cancers was different, including driver genes MET, CDKN2A/B, and PMS2. No difference was observed in terms of frequency on short variants or gene fusions in NSCLC. Citation Format: Yunfei Shi, Naiquan Mao, Xiao Ding, Jianji Guo, Gang Guo, Zheng Chen, Weiguang Gu, Lei Dai, Shiwang Wen, Hui Jia, Ziqiang Tian, Junping Shi, Taiyan Guo, Jicheng Yao, Fei Pang, Gungwei Chirn, Ming Yao. Comparison of gene copy number variations (CNV) in primary and metastatic lung cancers [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 3391.

e21144Background: Noninvasive methods, such as circulating tumor DNA (ctDNA) profiling, are required for real-time molecular monitoring of treatment, detection of recurrence, and tracking resistanc...

TCF21, a newly discovered gene, exhibits tumor suppressor function in a variety of tumors. This study aims to observe the effects of TCF21 on the proliferation, apoptosis and migration of A549 human lung adenocarcinoma epithelial cells.TCF21 was overexpressed in A549 cells via lentiviral transfection. Fluorescence-based quantitative polymerase chain reaction and Western blot analysis were used to analyze the expression of the target gene. Transwell, proliferation assay, and flow cytometry were applied to detect the effect of TCF21 overexpression on the migration, proliferation, and apoptosis of A549 cells after transfection.The proliferation and migration of A549 cells were inhibited, and the apoptotic rate was increased by overexpressing TCF21.The tumor suppressor gene, TCF21, significantly inhibits the proliferation and migration, as well as facilitates early apoptosis of A549 cells.背景与目的 转录因子21（transcription factor 21, TCF21）是新近发现的抑癌基因，其在多种肿瘤中具有抑癌功能，本研究旨在探讨TCF21基因对人肺癌A549细胞增殖、迁移和凋亡的影响。 方法 利用慢病毒转染技术在肺癌A549细胞中高表达TCF21基因，以荧光定量PCR、Western blot分析目的基因的表达，并采用Transwell、MTT法、流式细胞术检测TCF21高表达对A549迁移、增殖、凋亡的影响。结果 成功在肺癌细胞株A549中高表达TCF21，且高表达TCF21后A549的细胞生长和迁移能力受抑制、凋亡率增高。结论 抑癌基因TCF21可抑制A549细胞的增殖和迁移、诱导凋亡。

The association between excision repair cross complementing group 2 (ERCC2) Asp312Asn polymorphism and lung cancer has been reported by many articles recently, but the results were controversial and inconclusive. Therefore, a meta-analysis was conducted to assess the relationship between them. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. A total of 22 full studies with 20,101 subjects (8719 cases and 11,382 controls) were included in our research. The meta-analysis result showed that no significant association was found between ERCC2 Asp312Asn polymorphism and lung cancer in overall analysis (AA vs. GG, OR=1.023, 95% CI=0.824-1.270, p=0.838; AG vs. GG, OR=1.003, 95% CI=0.936-1.074, p=0.942; AA+AG vs. GG, OR=1.013, 95% CI=0.949-1.082, p=0.697; AA vs. AG+GG, OR=1.033, 95% CI=0.841-1.270, p=0.755). In subset analyses of stratified ethnicity, significantly increased risk was found among Asians (AA vs. GG, OR=3.212, 95% CI=1.518-6.795, p=0.002; AA vs. AG+GG, OR=3.174, 95% CI=1.500-6.712, p=0.003), whereas the association was not found among Caucasians under any genetic models. When analyses were conducted based on the study design, it indicated that the risk of lung cancer might be significantly increased in a hospital-based study (AA vs. GG, OR=1.323, 95% CI=1.096-1.596, p=0.004; AA+AG vs. GG, OR=1.109, 95% CI=1.000-1.229, p=0.050; AA vs. AG+GG, OR=1.285, 95% CI=1.076-1.535, p=0.006). In addition, a significantly increased risk for nonsmokers was detected under the dominant model (AA+AG vs. GG, OR=1.460, 95% CI=1.095-1.948, p=0.010). In conclusion, this meta-analysis suggested ERCC2 Asp312Asn polymorphism may increase the risk of lung cancer among Asians, whereas not among Caucasians.

hTERT and p16 are involved in oncogenesis and development of tumor. The aim of this study is to investigate the expression of human telomerase reverse transcriptase (hTERT) and p16 in non-small cell lung cancer (NSCLC).The quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and immunohistochemistry were applied to detect the hTERT and p16 in tissue of 21 cases of lung benign diseases and 117 of non-small cell lung cancer and adjacent tissues, respectively.hTERT mRNA levels from NSCLC in 117 patients and normal lung tissue in 21 normal controls were 2.937+/-0.836 and 2.042+/-0.378, respectively (t=-5.242, P0.01). Expression of p16 protein was observed in 85.7% of normal tissues, while 47.9% of lung cancer tissues showed p16 protein expression (P=0.004). The expression of hTERT mRNA was significantly correlated with the histology (P0.05); the expression of p16 protein was significantly correlated with the clinical stage, degree of differentiation and lymph node metastasis (P0.05). The significant correlation between the expression of hTERT and p16 (P0.05).The hTERT may be useful in clinical diagnosis of NSCLC. Expression of hTERT and p16 is related to the carcinogenesis and development of NSCLC.

Background Whether body mass index (BMI) is a significant risk factor for recurrence of primary spontaneous pneumothorax (PSP) remains controversial. The purpose of this study was to examine whether BMI and other factors are linked to risk of PSP recurrence. Methods A consecutive cohort of 273 patients was retrospectively evaluated. Patients were divided into those who experienced recurrence (n = 81) and those who did not (n = 192), as well as into those who had low BMI (n = 75) and those who had normal or elevated BMI (n = 198). The two pairs of groups were compared in terms of baseline data, and Cox proportional hazards modeling was used to identify predictors of PSP recurrence. Results Rates of recurrence among all 273 patients were 20.9% at 1 year, 23.8% at 2 years, and 28.7% at 5 years. Univariate analysis identified the following significant predictors of PSP recurrence: height, weight, BMI, size of pneumothorax, and treatment modality. Multivariate analyses identified several risk factors for PSP recurrence: low BMI, pneumothorax size ≥50%, and non-surgical treatment. Kaplan–Meier survival analysis indicated that patients with low BMI showed significantly lower recurrence-free survival than patients with normal or elevated BMI (P