Abstract. Collagen type XI α1 (COL11A1), a minor fibrillar collagen, has been demonstrated to be involved in cell proliferation, migration and the tumorigenesis of many human malignancies. Previous studies have shown that COL11A1 may be a valuable diagnostic marker for non-small cell lung carcinoma (NSCLC). However, its biological function in NSCLC progression remains largely unclear. In the present study, we investigated the expression levels of COL11A1 in different human NSCLC samples, and found that COL11A1 was overexpressed in NSCLC with lymph node metastasis and in recurrent NSCLC tissues. We also revealed that COL11A1 promoted the cell proliferation, migration and invasion of NSCLC cell lines in vitro. Furthermore, our results highlighted the importance of COL11A1 in chemoresistance to cisplatin. Mechanistically, we found that the effects of the overexpression of COL11A1 in NSCLC cells were mediated by Smad signaling. Collectively, our findings suggest that COL11A1 may sever as a biomarker for metastatic NSCLC, and can be used to predict recurrence after surgical resection. Therapeutic approaches targeting COL11A1 may facilitate the optimization of cisplatin treatment of NSCLC by overcoming chemoresistance. IntroductionLung cancer is the most common type of cancer, and is the leading cause of human cancer-related deaths (1,2). Non-small cell lung carcinoma (NSCLC) accounts for approximately 85% of all cases of human lung cancer, including all types of epithelial lung cancer except small cell lung carcinoma (SCLC) (3). Generally, the 5-year survival rate of lung cancer patients is approximately 15% (2). For patients with different stages of lung cancer, the 5-year relative survival rate varies dramatically from 49 to 2% (2,4). However, approximately 70% of patients with lung cancer were found to present with intrathoracic or extrathoracic metastasis at initial diagnosis (3,5). Thus, it is crucial to detect lung cancer at an early stage, and to suppress the spread of primary cancer.Currently, surgical resection remains the single most successful treatment for patients with early-stage NSCLC (6,7). However, despite optimal surgical treatment, approximately half of the patients with NSCLC develop recurrence and succumb to the disease, even though they present with histologically negative lymph nodes (8,9). While bone is the most common target of distant metastasis from lung cancer, recurrent NSCLC is often systemic (4,8). Although the mechanisms of recurrent NSCLC remain unclear, several molecules have been reported to predict the recurrence of NSCLC. These include EphA2 (EPH receptor A2) receptor tyrosine kinase, USP17 and DNA methylation markers (10-12).The collagen type XI α1 (COL11A1) gene encodes one of the two α chains of type XI collagen, a minor fibrillar collagen (13). As a major component of the extracellular matrix (ECM), collagens are involved in the regulation of multiple biological processes, including cell proliferation, differentiation and migration (14,15). Type XI collagen is a heterotrimer, ...

IntroductionHeparin-binding protein (HBP) is an antimicrobial protein stored in neutrophil granules and plays a role in endothelial permeability regulation. The aim was to assess the diagnostic and prognostic value of measuring HBP in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS).MethodsPlasma HBP was collected from 78 patients with ALI/ARDS, 28 patients with cardiogenic pulmonary edema (CPE) and 20 healthy volunteers at enrollment. Levels of HBP were measured by ELISA.ResultsPatients with ALI/ARDS had significantly higher median levels of HBP compared with patients with CPE (17.15 (11.95 to 24.07) ng/ml vs. 9.50 (7.98 to 12.18) ng/ml, P <0.001) at enrollment. There was no significant difference between CPE patients and healthy subjects in terms of HBP value (P = 0.372). The HBP levels of nonsurvivors was significantly higher than that of survivors (23.90 (14.81 to 32.45) ng/ml vs. 16.01 (10.97 to 21.06) ng/ml, P = 0.012) and multivariate logistic regression showed HBP (odds ratio =1.52, P = 0.034) was the independent predictor for 30-day mortality in patients with ALI/ARDS.ConclusionsPlasma HBP levels of ALI/ARDS patients were significantly higher than that of CPE patients. HBP was a strong prognostic marker for short-term mortality in ALI/ARDS.

Currently, chemotherapy with platinum-based drugs including cisplatin is the most effective therapy for the treatment of non-small cell lung carcinoma (NSCLC). However, the efficacy of chemotherapy is limited due to commonly developed drug resistance. Spindle and kinetochore-associated complex subunit 1 (SKA1) is part of a complex essential for stabilizing the attachment of spindle microtubules to kinetochores and for maintaining the metaphase plate during mitosis. In the present study, we aimed to investigate the role of SKA1 in the process of metastasis and drug resistance of NSCLC. We completed a series of experiments to investigate the function of SKA1 in NSCLC metastasis and drug resistance including qRT-PCR, immunohistochemistry and western blotting, as well as MTT, BrdU, wounded healing, Transwell and gelatin zymography assays. We demonstrated that the expression levels of SKA1 were elevated in NSCLC and were correlated with cancer progression and malignancy. We also reported that SKA1 positively regulated the proliferation and metastatic ability of NSCLC cells. In addition, we determined that SKA1 contributed to cisplatin resistance in NSCLC cells by protecting these cells from cisplatin-induced cell apoptosis. SKA1 also appeared to regulate the ERK1/2 and the Akt-mediated signaling pathways in NSCLC cells. SKA1 is required for metastasis and cisplatin resistance of non-small cell lung cancer.

No abstract