Comprehensive genomic and immunological characterization of Chinese non-small cell lung cancer patients.

Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72.5%) compared with squamous cell carcinoma (SQCC, 54.4%). The correlation of genomic alterations with immune signatures reveals that low immune infiltration was associated with EGFR mutations in ADC samples, PI3K and/or WNT pathway activation in SQCC. While KRAS mutations are found to be significantly associated with T cell infiltration in ADC samples. The SQCC patients with high antigen presentation machinery and cytotoxic T cell signature scores are found to have a prolonged overall survival time.

5-Aza-CdR can reverse gefitinib resistance caused by DAPK gene promoter methylation in lung adenocarcinoma cells.

To explore the relationship between death associated protein kinase (DAPK) gene promoter methylation and gefitinib resistance in Lung adenocarcinoma cell lines. EGFR-mutation lung adenocarcinoma cell lines PC9 and the gefitinib-resistant with T790M Mutation cell lines PC9/GR were chosen as cell models, and PC9/GR were treated with 5-aza-CdR (1 µmol/L). The experiments were divided into three groups: PC9 group, PC9/GR group and PC9/GR with 5-Aza-CdR pretreatment group. Treat three groups cell with different concentrations gefitinib, the cell proliferation was determined by MTT assay. The apoptotic rates were detected by flow cytometry. The methylation of DAPK gene promoter region was examined by methylation-specific PCR (MSP). The expressions of DAPK protein were detected by Western blot. MTT results showed that the half maximal inhibitory concentration (IC50) of PC9 and PC9/GR cell lines increase from 0.12 µmol/L to 8.52 µmol/L. But after treated with 5-aza-CdR, the IC50 of PC9/GR cell lines decrease to 4.35 µmol/L, and the resistance index (RI) decrease from 71 to 36 (P<0.05). Flow cytometry results showed that the apoptosis rate were 24.80% ± 0.28%, 12.70% ± 0.31%, 19.8% ± 0.15% respectively. MSP results showed that DAPK gene promoter region was un-methylated in PC9 cells and methylated in PC9/GR cells, when treated with 5-aza-CdR, DAPK gene promoter region was partly methylated in PC9/GR cells (P<0.05). Western blot results showed that the levels of DAPK protein were reduced significantly in PC9/GR cell lines compared with PC9, and after treated with 5-aza-CdR, the expression levels of DAPK protein in PC9/GR were increased (P<0.05). In conclusion, DAPK gene promoter methylation may contribute to the downregulation of DAPK gene and protein, and consequently affect the sensitivity of gefitinib in lung adenocarcinoma lines, induced gefitinib resistance. But 5-Aza-CdR can reverse gefitinib resistance by demethylation of DAPK gene promoter.

Thoracoscopic lobectomy in a lung cancer patient with severe hemophilia: A case report.

Hemophilia is a hereditary disease with impaired blood coagulation due to a genetic deficiency of blood coagulation factors. Hemophilia often causes spontaneous life-threatening bleeding, so patients with hemophilia are often not suitable for any surgery that may cause iatrogenic bleeding and threaten the life of the patient. Therefore, surgery in lung cancer patients with hemophilia is extremely rare. The present study reported the case of a lung cancer patient with hemophilia who presented with a persistent cough. A mass was revealed by computed tomography and the patient underwent a successful thoracoscopic right lower lobectomy. The study discusses the patient's diagnosis and treatment options for hemophilia A and lung cancer, including indications for thoracoscopic lobectomy, pre-operative preparation and post-operative care, and other treatment options are discussed. The literature is also reviewed on this subject.

Sanguinarine-induced apoptosis in lung adenocarcinoma cells is dependent on reactive oxygen species production and endoplasmic reticulum stress.

Sanguinarine (SAN), an alkaloid isolated from plants of the Papaveraceae family, is a compound with multiple biological activities. In the present study, we explored the anticancer properties of SAN in lung cancer using the human lung adenocarcinoma cell line SPC-A1. Our results revealed that SAN inhibited SPC-A1 cell growth and induced apoptosis in a dose-dependent manner. We found that SAN triggered reactive oxygen species (ROS) production, while elimination of ROS by N-acetylcysteine (NAC) reversed the growth inhibition and apoptosis induced by SAN. SAN-induced endoplasmic reticulum (ER) stress resulted in the upregulation of many genes and proteins involved in the unfolded protein response (UPR) pathway, including glucose-regulated protein 78 (GRP78), p-protein kinase R (PKR)-like ER kinase (PERK), p-eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein homologous protein (CHOP). Blocking ER stress with tauroursodeoxycholic acid (TUDCA) markedly reduced SAN-induced inhibition of growth and apoptosis. Furthermore, TUDCA decreased SAN-induced ROS production, and NAC attenuated SAN-induced GRP78 and CHOP expression. Overall, our data indicate that the anticancer effects of SAN in lung cancer cells depend on ROS production and ER stress and that SAN may be a potential agent against lung cancer.

Clinicopathological characteristics and prognosis of patients with adenosquamous lung carcinoma.

This study was aimed to characterize clinicopathological features and prognosis of patients with adenosquamous lung carcinoma (ASC). Among the 2531 patients with lung cancer who underwent surgery between January 2000 and June 2012 in our hospital, 59 were histologically diagnosed as having ASC. The clinicopathological features and follow-up data of ASC patients were collected and analyzed statistically. Superior lobectomy was accomplished in 40 patients, middle and inferior lobectomy in 3, lobectomy plus partial resection of contralateral lung in 5, partial lung resection in 4, and pneumonectomy in 7. Moreover, 22 cases were found to be adenocarcinoma-predominant, and 18 to be squamous cell carcinoma-predominant. The median survival time was 13.6 months, and the 1-, 3-, and 5-year survival rates were 59.9%, 36.4% and 31.2%, respectively. Of the 52 cases with tissue specimens available, 11 had an EGFR mutation (21.2%) and 2 had a KRAS mutation (3.8%). Multivariate analysis showed that histology subtype, pleural invasion, TNM stage, and postoperative treatment were all independent prognostic factors. The data from the current study demonstrated that SCC-predominant histology represents a better prognosis of ASC. Histology subtype, pleural invasion, TNM stage, and postoperative treatment are independent prognostic factors for ASC and adjuvant therapy may help control the disease.

Prognostic significance of serum microRNA-210 levels in nonsmall-cell lung cancer.

OBJECTIVE: To investigate the levels of microRNA-210 (miR-210) in the serum of patients with nonsmall-cell lung cancer (NSCLC) and to determine whether there was a correlation with the prognosis of NSCLC patients following cisplatin-based chemotherapy. METHODS: Quantitative real-time reverse transcription-polymerase chain reaction was used to measure the serum levels of miR-210 in patients with NSCLC and healthy age-matched control subjects. Correlations between serum miR-210 levels and clinicopathological factors and prognosis were investigated. RESULTS: Serum miR-210 was significantly upregulated in 60 patients with NSCLC compared with 30 healthy control subjects. Higher serum miR-210 levels were significantly correlated with the clinical stage and the presence of regional lymph node metastasis in patients with NSCLC. Serum miR-210 levels in patients that achieved a partial response following cisplatin-based chemotherapy were significantly lower than in patients with stable or progressive disease, and were similar to those in healthy control subjects. CONCLUSIONS: These findings suggest that serum miR-210 levels might be a novel diagnostic and prognostic marker of NSCLC.