EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non-small cell lung carcinoma via WNT signalling pathway.

DNA methylation is important for lung cancer prognosis. In this work, it is aimed to seek novel biomarkers with DNA methylation-expression-pathway pattern and explore its underlying mechanism. Prognostic DNA methylation sites and mRNAs were screened in NSCLC data set from TCGA, and further validated using the samples retrospectively collected, and EXT1 was identified as a potential target. Gene body methylation of three CpG sites (cg03276982, cg11592677, cg16286281) on EXT1 was significantly associated with clinical outcome, and the EXT1 gene expression also predicted prognosis. The expression level of EXT1 was also correlated with its DNA methylation level. This observation was further validated in a new data set consist of 170 samples. Knocking down of EXT1 resulted in decreased proliferation and migration. EXT1 targets were analysed using GSEA. It is found that the WNT signalling is the potential downstream target of EXT1. Further analyses revealed that the EXT1 targets the beta-catenin and effect migration rate of NSCLC cell lines. The WNT signalling inhibitor, XAV-939, effectively disrupted the migration promotion effect induced by EXT1. In summary, EXT1 methylation regulates the gene expression, effects the proliferation and migration via WNT pathway and predicted a poor prognosis for NSCLC.

Apatinib plus Chemotherapy as a Second-Line Treatment in Unresectable Non-Small Cell Lung Carcinoma: A Randomized, Controlled, Multicenter Clinical Trial.

LESSONS LEARNED: The efficacy of second-line treatment for advanced non-small cell lung carcinoma (NSCLC) without a sensitizing driver gene mutation is still unsatisfactory. The combination of apatinib and chemotherapy improved progression-free survival in the second-line therapy of advanced NSCLC without a sensitizing mutation. This study offers a new treatment strategy for second-line treatment of such patients but requires confirmation in a larger multi-institutional trial. BACKGROUND: This study explored the efficacy and safety of apatinib combined with single-agent chemotherapy versus single-agent chemotherapy in the second-line treatment of advanced non-small-cell lung carcinoma (NSCLC) without driver mutations. METHODS: In this double-arm, open label, exploratory clinical study, we enrolled patients with unresectable locally advanced or advanced NSCLC without driver mutations that had progressed following first-line chemotherapy. The subjects were allocated into an experimental group and a control group by 2:1. The experimental group received apatinib combined with four cycles of docetaxel or pemetrexed until disease progression, intolerable toxicity, or discontinuation at the patient' request. The control group only received four cycles of docetaxel or pemetrexed. The primary endpoints were progression-free survival (PFS), and the secondary endpoints were overall survival (OS), disease control rate (DCR), and safety. RESULTS: Thirty-seven patients were enrolled. The efficacy of 33 patients was evaluated. The median PFS was 5.47 versus 2.97 months, the DCR was 95% versus 73%, and the objective response rate (ORR) was 27% versus 9% in the experimental versus control group. The OS was still under follow-up. The most common adverse effects included hypertension, hand-foot skin reaction (HFSR), and fatigue. CONCLUSION: Apatinib combined with single-agent chemotherapy may be a novel option for second-line treatment of advanced NSCLC.

A Five-gene Signature for Predicting the Prognosis of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is a kind of tumor with high incidence and its treatment situation is still very difficult despite the constant renewal and development of treatment methods. OBJECTIVE: To assist the prognosis, monitoring and survival of CRC patients with a model. METHODS: In this study, we established a new prognostic model for CRC. Four groups of CRC data were accessed from the GEO database, and then differential analysis (logFoldChange>1, adjust- P<0.05) was carried out by using the limma package along with the RobustRankAggreg package used to identify the overlapping differentially expressed genes (DEGs). Univariate and multivariate Cox regression analyses were performed on the DEGs to screen the genes related to the patient's prognosis, and a five-gene prognostic prediction model (including RPX, CXCL13, MMP10, FABP4 and CLDN23) was constructed. Then, we further plotted ROC curves to evaluate the predictive performance of the five-gene prognostic signature in the TCGA data sets (the AUC values of 1, 3, 5-year survival were 0.68, 0.632, 0.675, respectively) and an external independent data set GSE2962 (the AUC values of 1, 3, 5-year survival were 0.689, 0.702, 0.631, respectively). RESULTS: The results showed that the model could effectively predict the prognosis of CRC patients, which provides a robust predictive model for the prognosis of CRC patients. CONCLUSION: The model could effectively predict the prognosis of CRC patients, which provides a robust predictive model for the prognosis of CRC patients.

Response of Metastatic Chordoma to the Immune Checkpoint Inhibitor Pembrolizumab: A Case Report.

Chordoma is a rare primary bone tumor that exhibits insensitivity to radiotherapy and chemotherapy and has a poor prognosis. Currently, resection is the primary treatment for affected patients, but the subsequent rate of recurrence is high, and both overall survival (OS) and progression-free survival (PFS) are consequentially relatively short. This case report describes a patient who was diagnosed with metastatic chordoma that was found to possess the A1209fs mutation of the PBRM1 gene, which may be associated with beneficial responses to immunotherapies. The patient received pembrolizumab, an immune checkpoint inhibitor (ICI) that targets the PD-1 receptor of lymphocytes, as second-line therapy, which he tolerated well (the most frequent adverse events were abnormal liver function and hyperglycemia, both of which were only grades 1-2), and achieved a PFS duration of 9.3 months. We hope these results will promote further research that will clarify the mechanisms underlying this beneficial response and that will further explore the use of immunotherapies in this population.