BackgroundGround‐glass nodules (GGNs), which are possible precursors of lung cancer, attract increasing attention. Many studies have attempted to identify the characteristic imaging features of GGNs for their qualitative diagnosis; however, the comprehension of GGNs remains controversial. We performed this study to identify imaging characteristics helpful to the differential diagnosis of solitary GGNs.MethodsWe retrospectively evaluated 112 solitary GGNs resected from 112 patients, pathologically examined after surgical resection. Imaging features of the GGNs, such as size, shape, a solid component, lobulation, spiculation, vascular convergence sign, pleural tag, and air cavity density, were assessed. Differences between malignant and benign nodules were analyzed using binary logistic regression analysis.ResultsOf the 112 GGNs, 82 were malignant and 30 were benign. A solid component, vascular convergence sign, and a larger diameter were risk factors for malignancy, with a sensitivity, specificity, and accuracy of 93.9%, 60.0%, and 84.8%, respectively. Lobulation, spiculation, air cavity densities, and pleural tags were also important indicators of malignancy, with positive predictive values of 93.5%, 83.3%, 91.7%, and 87.2%, respectively.Conclusion GGNs with a solid component, vascular convergence sign, and a larger diameter are highly suggestive of malignancy. The possibility of a neoplasm should also be considered in the case of GGNs that show lobulation, spiculation, air cavity densities, or pleural tags. To obtain a comprehensive and accurate analysis of the nodules, three‐dimensional reconstruction is highly recommended.

Neoadjuvant erlotinib was well tolerated and may improve the radical resection rate in this patient population. Next-generation sequencing may predict outcomes with preoperative TKIs.

Capture-based next-generation sequencing (NGS) is a potentially useful diagnostic method to measure tumor tissue DNA in blood as it can identify concordant mutations between cell-free DNA (cfDNA) and primary tumor DNA in lung cancer patients. In this study, the sensitivity, specificity and accuracy of capture-based NGS for detecting ALK fusion in plasma cfDNA was assessed. 24 patients with tissue ALK-positivity and 15 who did not harbor ALK fusion were enrolled. 13 ALK-positive samples were identified by capture-based NGS among the 24 samples with tissue ALK-positivity. In addition to EML4-ALK, 2 rare fusion types (FAM179A-ALK and COL25A1-ALK) were also identified. The overall sensitivity, specificity and accuracy for all cases were 54.2%, 100% and 71.8%, respectively. For patients without distant metastasis (M0-M1a) and patients with distant metastasis (M1b), the sensitivities were 28.6% and 64.7%, respectively. In the 15 patients who received crizotinib, the estimated median PFS was 9.93 months. Thus, captured-based NGS has acceptable sensitivity and excellent specificity for the detection of ALK fusion in plasma cfDNA, especially for patients with distant metastasis. This non-invasive method is clinically feasible for detecting ALK fusion in patients with advanced-stage NSCLC who cannot undergo traumatic examinations or have insufficient tissue samples for molecular tests.

FKBP3 is a member of FK506-binding proteins (FKBPs). Little is known about the expression and functional role(s) of FKBP3 in non-small cell lung cancer (NSCLC). In the present study, we demonstrated up-regulation of FKBP3 expression, both at mRNA and protein levels, in NSCLC samples which closely correlated with poor survival in NSCLC patients. In vitro and in vivo experiments revealed that FKBP3 could promote NSCLC cell proliferation. Furthermore, knockdown of FKBP3 significantly decreased histone deacetylase 2 (HDAC2) expression and increased p27 (a cell cycle inhibitor) expression. HDAC2 modulated the acetylation of histone H3K4 by directly binding to the p27 promoter. The proliferation-promoting effect of FKBP3 was dependent on HDAC2 and inhibited by p27. Also, FKBP3 induced HDAC2 promoter activity via inhibiting the ubiquitination of transcription factor Sp1. Additionally, we identified miR-145-5p as a regulator of FKBP3. miR-145-5p overexpression suppressed cell proliferation of NSCLC cells which was abrogated by FKBP3 overexpression. Taken together, our data clearly show that FKBP3/Sp1/HDAC2/p27 control cell proliferation during NSCLC development.

Non-small cell type lung cancer (NSCLC) is the most common malignancy and the leading cause of cancer related mortality. In this study, serine/threonine kinase 39 (STK39) was identified as an up-regulated gene in NSCLC tissues by next-generation RNA sequencing. Although STK39 gene polymorphisms may be prognostic of overall survival in patients with early stage NSCLC, the roles of STK39 in NSCLC cancer are poorly understood. In the current study, Genome Set Enrichment Analysis (GSEA) on the RNA-seq data of NSCLC specimens indicated that cancer-related process and pathways, including metastasis, cell cycle, apoptosis and p38 pathway, were significantly correlated with STK39 expression. STK39 expression was significantly increased in NSCLC cases and its protein expression was positively correlated with the poor tumor stage, large tumor size, advanced lymphnode metastasis and poor prognosis. Down-regulation of STK39 in NSCLC cells significantly decreased cell proliferation by blocking of cell cycle and inducing apoptosis. We also found that STK39 knockdown in NSCLC cells remarkably repressed cell migration and invasion. On the contrary, overexpression of STK39 in NSCLC cells had inverse effects on cell behaviors. Taken together, STK39 acts as a tumor oncogene in NSCLC and can be a potential biomarker of carcinogenesis.

Anlotinib is a multitargeted antiangiogenic drug, and its clinical predictor for responsive non‐small cell lung cancer (NSCLC) patients is still elusive. Here, tumor‐specific target capture is used to profile the circulating DNA of ALTER0303 (evaluating NSCLC clinical antitumor efficacy through anlotinib therapy) study participants. The results indicate that patients receiving no benefit can be mainly excluded via analysis of ARID1A and BRCA2 genetic profiling. For patients with no durable benefit and durable clinical benefit patients, three predictors: germline and somatic mutation burden (G+S MB), nonsynonymous and synonymous mutation burden (N+S MB), and unfavorable mutation score of circulating DNA profiling are identified. Through integrating the advantages and disadvantages of three independent predictors, the tumor mutation index (TMI) is established as a prediction model and the patients who are very likely to benefit more from anlotinib therapy are identified. Furthermore, the IDH1exon 4 mutation is identified as an unfavorable factor for anlotinib therapy under TMI‐based stratification, and the TMI plus IDH1exon 4 mutation status potentially predicts response to anlotinib. Collectively, this study provides a circulating DNA sequencing–based stratification method for identifying anlotinib responders via a noninvasive approach, and thus potentially improves the clinical outcome of NSCLC patients receiving third‐line therapy.

Background The optimal neoadjuvant regimen for locally advanced resectable non-small cell lung cancer (NSCLC) remains controversial. EGFR inhibitors have significantly improved survival in patients with EGFR-mutant advanced NSCLC. However, their efficacy in neoadjuvant settings, particularly for treating locally advanced NSCLC, remains unclear. We compared the clinical benefits of chemotherapy and erlotinib as neoadjuvant therapy for stage IIIA NSCLC. Method Thirty-one treatment-naïve Chinese patients with stage IIIA NSCLC were enrolled. Patients without EGFR mutation received cisplatin-based doublet chemotherapy (n = 16; N-chemo group) while EGFR-mutant patients received erlotinib (n = 15; N-TKI group) as neoadjuvant therapy. Results After completing neoadjuvant treatment, 12 and 8 patients from the N-TKI and N-chemo groups underwent surgery, respectively. Our data revealed that patients who received erlotinib had a marginally better clinical objective response rate (67% vs. 19%), pathological response rate (67% vs. 38%), and overall survival (51.0 months vs. 20.9 months) compared with those who received chemotherapy. Furthermore, patients in the N-TKI group had a significantly greater reduction in tumor diameter, serum carcinoembryonic level, and maximum allelic fraction. Conclusion Our findings demonstrate that erlotinib is an effective neoadjuvant regimen in patients with EGFR-mutant locally advanced NSCLC, paving the way for its extended use in neoadjuvant settings. [ClinicalTrials.gov identifier: NCT01217619]

Transmembrane protein 48 (TMEM48), localized to nuclear pore complexes (NPCs), has been reported crucial for NPC assembly. Alterations in NPC members have been reported in several malignancies. The present study was aimed to elucidate the expression and biological function of TMEM48 in non-small cell lung carcinoma (NSCLC). Here, TMEM48 expression level was higher in NSCLC tissues than that in the adjacent normal tissues. Moreover, higher TMEM48 expression was correlated with a more advanced tumor stage, lymph node metastasis, bigger tumor size tumor stage, and shorter survival time. Knockdown of TMEM48 in NSCLC cell lines, A549 and H1299, inhibited cell proliferation and significantly increased cells population in G1 phase. Gene set enrichment analysis (GSEA) showed that cell cycle pathway was correlative with the TMEM48 expression. Additionally, real-time PCR and western blot analysis revealed that several cell cycle and DNA replication genes, including Cyclin B1, CDK1, CDC6, PCNA, and RCF4, were reduced after TMEM48 knockdown. Additionally, inhibition of TMEM48 in NSCLC cells significantly stimulated cell apoptosis, while notably repressed cell adhesion, migration, invasion, and tumorigenicity in nude mice. Our data provide insight into the biological relevance of TMEM48 in NSCLC progression and highlight its usefulness as a prognostic factor and potential therapeutic target in NSCLC.