Background: Anlotinib has been demonstrated its anti-tumor efficacy on non-small cell lung cancer (NSCLC) in clinical trials at 3rd line. However, anlotinib resistance occurs during its administration, and the underlying mechanism is still unclear. Methods: Anlotinib resistant lung cancer cell line NCI-H1975 was established in vitro. Toxicologic effects undergoing anlotinib stress were observed upon NCI-H1975 cells and anlotinib resistant NCI-H1975 cells, respectively. Transcriptome profiling was performed to screen anlotinib resistance-associated genes between NCI-H1975 cells and anlotinib resistant NCI-H1975 cells. Functional assays were performed to examine the correlations between CXCL2 gene expression and anlotinib resistance. Results: We found anlotinib inhibits cell proliferation and cell viability in NCI-1975 cells, whereas it attenuates these activities in anlotinib resistant NCI-H1975 cells. Transcriptome profiling analysis identified 769 anlotinib-responsive genes enriched in the biological processes of microtubule-based process, cytoskeleton organization, and wound healing. Furthermore, we found 127 genes are associated with anlotinib resistance. In particular, we demonstrated that CXCL2 contributes to anlotinib resistance in NCI-H1975 cells. Conclusions: This study suggested that CXCL2 is involved in anlotinib resistance in NCI-H1975 cells and provided an insight for understanding the resistant mechanism of anlotinib.

The aim of this study was to determine the prognostic value of lymph node status in patients with pathologic N2 (pN2) stage IIIA small cell lung cancer (SCLC). A total of 163 consecutive pN2 stage IIIA SCLC patients who underwent pulmonary resections and systematic lymphadenectomies at Shanghai Chest Hospital between January 2006 and June 2014 were enrolled. We retrospectively analyzed the potential clinicopathologic factors that influenced survival, including the node levels (single or multiple-station) and the node-spreading patterns (skip N2 or non-skip N2). The prognostic significance was examined by Cox regression analysis. The median overall survival (OS) was 23.7 months. Multiple-station lymph node metastasis indicated a poorer prognosis than single-station involvement (p = 0.003). Skip metastasis did not appear to influence survival (p = 0.099). With respect to the station of lymph node metastasis, the OS was only related to the involvement of the subcarinal node, regardless of tumor location (p < 0.05). Multivariate analysis showed two statistically significant risk factors for survival, including multiple-station lymph node and subcarinal node metastasis (hazard ratio [HR] = 1.76, 95% confidence interval [CI]:1.11–2.78, p = 0.015; HR = 1.61, 95% CI: 1.03–2.50, p = 0.036, respectively). Multiple-station N2 metastasis and involvement of the subcarinal node predicted poor prognosis in pN2 stage IIIA SCLC patients, which may profoundly influence therapeutic decisions.

Background: Currently, many detection methods have high sensitivity to the diagnosis of lung cancer. However, some postoperative patients with pulmonary nodules are eventually diagnosed as having benign nodules. The ideal evaluation of an individual with a pulmonary nodule would expedite therapy for a malignant nodule and minimize testing for those with a benign nodule. Methods: This case–control study is designed to explore the relationship between ACE1 rs4646994 polymorphism and the risk of lung cancer in patients with pulmonary nodules, for which 400 individuals with lung cancer and benign pulmonary nodules were included. A DNA extraction kit was used to extract DNA from peripheral blood. The relationship between ACE1 rs4646994 and the risk of lung cancer in patients with pulmonary nodules was determined by the chi-square test, logistic regression analysis and cross analysis. Results: The results showed that after adjusting for age and gender confounding factors, the risk of lung cancer in patients with pulmonary nodules carrying the DD genotype was more than three times that of the I carriers (II + ID) genotype (OR = 3.035, 95% CI, 1.252–7.356, p = 0.014). There was no significant difference between lung squamous cell carcinoma and lung adenocarcinoma in the polymorphism of ACE1 rs4646994 (p > 0.05). We also found that the ACE1 rs4646994 DD genotype frequency was inversely correlated with the risk of EGFR mutation in lung adenocarcinoma patients. Conclusions: Our study indicated that ACE1 rs4646994 polymorphism increases the risk of lung cancer in patients with pulmonary nodules from China.

Background: Currently, many detection methods have high sensitivity to the diagnosis of lung cancer. However, some postoperative patients with pulmonary nodule were eventually diagnosed as benign nodules. The ideal evaluation of an individual with a pulmonary nodule would expedite therapy for a malignant nodule and minimize testing for those with a benign nodule.Methods: This case-control study is designed to explore the relationship between ACE1 rs4646994 polymorphism and the risk of lung cancer in patients with pulmonary nodules, 400 individuals with lung cancer and benign pulmonary nodules were included. A DNA extraction kit was used to extract plasm DNA from peripheral blood. The relationship between ACE1 rs4646994 and the risk of lung cancer in patients with pulmonary nodules was determined by chi-square test, logistic regression analysis and cross analysis. Results: The results showed that the DD genotype of ACE1 rs4646994 may increase the risk of lung cancer in patients with pulmonary nodules, and this correlation was more significant in the female subgroup. In the age stratification analysis, it was found that the risk of lung cancer was significantly increased in the DD genotype of ACE1 rs4646994 in the older subgroup (> 45 years). In addition, the possibility of EGFR mutation in lung adenocarcinoma patients with ACE1 rs4646994 DD genotype was lower than that of II or ID genotype carriers. Conclusions: Our study indicated that ACE1 rs4646994 polymorphism increases the risk of lung cancer in patients with pulmonary nodules from China.