Expression and role of FKBPL in lung adenocarcinoma.

Dysregulated expression of FK506-binding protein like (FKBPL) has been demonstrated to play crucial roles in tumour development. However, the role of FKBPL in lung adenocarcinoma (ADC) remains unclear. Using immunohistochemical staining, we showed that FKBPL expression was significantly lower in lung ADC than the normal tissues (P < 0.0001). Patients with well or moderately differentiated tumours have higher FKBPL expression compared with patients with poor differentiated tumours (P = 0.037). However, no significant associations were found between FKBPL expression and other clinicopathological variables (P > 0.05 for all). Cox univariate analysis showed that high FKBPL expression was correlated with prolonged overall survival (OS) (P = 0.010). Kaplan-Meier analysis further confirmed that the FKBPL-low group showed a significantly shorter OS than the FKBPL-high group (P = 0.0081). FKBPL expression was not shown as an independent prognostic factor for OS in the multivariate analysis (P = 0.063). Moreover, our study demonstrated that FKBPL could suppress the proliferation of lung ADC cells by delaying cell cycle G1/S phase transition. In addition, FKBPL resulted in increased apoptosis in lung ADC cells. Using the Human Apoptosis Array Kit, we observed that overexpression of FKBPL in lung ADC A549 cells significantly decreased the anti-apoptotic proteins, including heat shock protein 32 (HSP32), heat shock protein 27 (HSP27), and paraoxonase-2 (PON2). FKBPL depletion significantly attenuated the pro-apoptotic protein, phospho-p53 (S46), in lung ADC H1975 cells. These new findings provide an experimental basis for further theoretical investigation of lung ADC.

The combination of preoperative fibrinogen-to-albumin ratio and postoperative TNM stage (FAR-TNM) predicts the survival in gastric cancer patients after gastrectomy.

OBJECTIVE: There are many factors that affect the survival of patients with gastric cancer, such as TNM stage, the patient's nutritional status, inflammation, and so on. In this study, the prognostic significance of preoperative fibrinogen-to-albumin ratio (FAR) and postoperative TNM staging in patients with gastric cancer was retrospectively studied. METHODS: A total of 265 patients (surgery dates from January 2007 to December 2013) were included in this retrospective study. All the patients were confirmed by pathology after operation. Categorical variables were compared using the χ2 test. Kaplan-Meier and log-rank tests were used for survival analysis. Cox proportional hazard models were used to assess prognostic factors. Nomogram was applied to predict the prognosis of overall survival (OS). RESULTS: The higher the FAR value, the more lymph node metastasis, the later the TNM stage, and the shorter the survival time. We established a new scoring system, the FAR-TNM score, which combined FAR and TNM stage. The FAR-TNM score was significantly related to tumor location, tumor size, Bormann types, differentiation, operative type, vascular invasion, nerve invasion, depth of invasion, lymphatic metastasis, and advanced TNM stage. Multivariate Cox regression analysis demonstrated that tumor location, TNM stage, adjuvant chemotherapy, and FAR-TNM score were independent prognostic elements for OS in patients with GC. CONCLUSIONS: The FAR-TNM score was a valuable independent prognostic indicator for GC patients after surgery, which can help clinicians to assist the treatment and long-term management of patients with gastric cancer.

Over-Expression of ARID3B Suppresses Tumor Progression and Predicts Better Prognosis in Patients With Gastric Cancer.

BACKGROUND: ARID3B (AT-rich interaction domain 3B) has been demonstrated to be associated with the progression and patient prognosis of several human tumors. We conducted the present study to investigate the biological behavior and clinical relevance of ARID3B in gastric cancer (GC). METHODS: Detection of the expression level in GC tissues and cell lines were performed by Western blot and immunohistochemistry. We also retrospectively analyzed the correlation of ARID3B with clinicopathological characteristics and patient prognosis in gastric cancer. The biological functions of ARID3B in GC cells were further explored by transwell migration assays, wound healing assays and cell proliferation assay. RESULTS: The present study suggested that the expression of ARID3B was significantly lower in GC tissues than in adjacent normal tissues. IHC staining in tissues of 406 GC patients from training and validation sets verified that ARID3B over-expression correlated with clinicopathological features, such as degree of differentiation and clinical stage. Meanwhile, ARID3B was proved to be an independent prognostic factor for GC prognosis. Furthermore, over-expression of ARID3B suppressed proliferation in GC cells according CCK8 assay. We found that over-expression of ARID3B inhibited GC cell migration by transwell assay and wound healing assay. Furthermore, EMT markers were detected in ARID3B over-expression GC cells, which showed that ARID3B may inhibit metastasis of GC cells. CONCLUSION: Our results firstly revealed that the expression level of ARID3B was closely correlated with clinicopathological features and may serve as an independent prognostic factor for GC patients. More importantly, ARID3B could suppress GC progression, including cell proliferation, migration and metastasis.

Role of DEP domain-containing protein 1B (DEPDC1B) in epithelial ovarian cancer.

Aberrant expression of DEPDC1B (DEP domain-containing protein 1B) has been shown to be associated with various types of malignant tumors. However, little is known about the role of DEPDC1B in epithelial ovarian cancer (EOC). The purpose of this study was to investigate the expression and role of DEPDC1B in EOC. Immunohistochemical staining of 60 high-grade serous ovarian cancer (HGSOC) showed that DEPDC1B expression was associated with response to first line chemotherapy, and DEPDC1B expression was higher in platinum-resistant patients than in platinum-sensitive patients. However, there was no association between DEPDC1B expression and age, preoperative CA125 level, ascites status, location, FIGO stage, and residual disease. Furthermore, our study demonstrated that increased DEPDC1B expression was correlated with reduced overall survival (OS) and progression-free survival (PFS) time in patients with HGSOC. Multivariate analysis showed that DEPDC1B independently predicted OS in patients with HGSOC. However, DEPDC1B expression was not an independent prognostic factor for PFS in patients with HGSOC. Moreover, our study demonstrated that DEPDC1B could promote the proliferation of OVCAR3 and SKOV3 cells by enhancing AKT phosphorylation at Ser473. Treatment with MK2206 and LY294002 significantly suppressed cell proliferation that is induced by DEPDC1B up-regulation in both OVCAR3 and SKOV3 cells. Together, these results revealed that DEPDC1B was an independent prognostic factor for OS in patients with HGSOC, and DEPDC1B may promote the proliferation of EOC cells via enhancing AKT phosphorylation at Ser473.

PD-L1 Expression and Intra-Tumoral CD8+ T Lymphocytes in Esophageal Carcinosarcoma.

We detected PD-L1 and intra-tumoral CD8+ T lymphocytes (CD8+ TIL) in 19 patients with esophageal carcinosarcoma (ECS). The median follow-up period of these patients was 43 months, and the three- and five-year survival rates were 78.9 and 63.2%, respectively. No statistically significant correlation was observed between PD-L1 and CD8+ TIL in sarcomatous components(SC) (r = -0.262, p = 0.279) and epithelial carcinomatous (EC) (r = 0.055, p = 0.824). This study examined the immunological markers in ECS for the first time. PD-L1 is highly expressed in the SC and is associated with a poorer prognosis.

Comprehensive analysis of differentially expressed lncRNAs as diagnostic and prognostic markers for colorectal cancer.

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Recent studies had revealed the important roles of long non-coding RNAs (lncRNAs) in a variety of human cancers, including CRC. However, the molecular mechanisms associated with CRC remain largely undetermined. In the current study, the GSE21510 dataset was analyzed to identify differentially expressed mRNAs and lncRNAs in CRC samples. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway bioinformatics analysis. Furthermore, protein-protein interaction networks were constructed to reveal interactions among differentially expressed proteins. Kaplan-Meier analysis was subsequently performed to determine the association between key lncRNA expression and the overall survival of patients with CRC. A total of 107 upregulated lncRNAs and 43 downregulated lncRNAs were identified in CRC. A lncRNA mediated co-expression network was also constructed in CRC. Bioinformatics analysis indicated that lncRNAs were associated with a series of biological processes, including 'xenobiotic glucuronidation', 'rRNA processing', 'sister chromatid cohesion', 'cell proliferation', 'mitotic nuclear division' and 'cell cycle regulation'. Furthermore, a higher expression of small nucleolar RNA host gene 17, tetratricopeptide repeat domain 2B-antisense RNA (AS) 1, erythrocyte membrane protein band 4.1 like 4A-AS2, deleted in lymphocytic leukemia 2, and a lower expression of muscle blind like splicing regulator 1-AS1 and LOC389332 were associated with shorter overall survival time in CRC samples. The present study provides useful information that can be used in the identification of novel biomarkers for CRC.

Expression and significance of ETFDH in hepatocellular carcinoma.

The ETFDH (electron transfer flavoprotein dehydrogenase) gene mutations are reported to be a major cause of riboflavin-responsive multiple acyl-coenzyme A dehydrogenation deficiency (MADD). However, the role of ETFDH in the prognosis of hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the expression of ETFDH in HCC. Immunohistochemical staining of the 207 HCC tissue microarray showed that expression of ETFDH was significantly decreased in HCC compared with the matching noncancerous hepatic tissues (P < 0.001). Moreover, ETFDH expression levels were found to be correlated with AFP levels (P = 0.011). Intriguingly, ETFDH expression levels were significantly lower in poorly differentiated or undifferentiated HCCs as compared to the well or moderately differentiated cases (P = 0.001). Kaplan-Meier analysis revealed that low tumor expression of ETFDH was associated with a poorer overall survival in patients with HCC (P = 0.024). Furthermore, multivariate analysis showed that ETFDH (P = 0.047) was an independent predictor of overall survival. Our findings may shed new light on the identification of new prognostic marker for HCC.

High Kpnß1 expression promotes non-small cell lung cancer proliferation and chemoresistance via the PI3-kinase/AKT pathway.

Karyopherin ß1 (Kpnß1), also known as importin-ß, is part of the karyopherin superfamily of nuclear transport proteins. Kpnß1 is an oncogene that is overexpressed in various human cancers. Recent studies have showed that Kpnß1 is one of the leading causes of cancer-related deaths in the world. However, the role of Kpnß1 in non-small cell lung cancer (NSCLC) remains uncertain. In this study, we used western blotting to show that Kpnß1 expression is higher in lung-cancer tissues and cells, and immunohistochemistry analysis revealed that Kpnß1 was significantly associated with the clinicopathological features of NSCLC. Kaplan-Meier analysis showed that elevated Kpnß1 expression correlated with a poor prognosis in NSCLC patients. Serum starvation-refeeding experiments and Kpnß1-shRNA transfection assays revealed that elevated Kpnß1 expression promoted cell proliferation and reduced sensitivity to cis-diamminedichloroplatinum. Immunoprecipitation assays showed that Kpnß1 interacts with PI3 K to activate the PI3-kinase/AKT pathway, leading to enhanced cell survival and drug resistance in NSCLC cells. Collectively, our findings suggest that Kpnß1 plays a significant role in NSCLC progression and chemoresistance. Our study provides new insights for targeted therapy to treat NSCLC.

Synthesis of 2-Sulfenylindenones via One-Pot Tandem Meyer-Schuster Rearrangement and Radical Cyclization of Arylpropynols with Disulfides.

A tandem annulation of arylpropynols with disulfides has been developed for the synthesis of 2-sulfenylindenone derivatives. The reaction pathway involves one-pot tandem Meyer-Schuster rearrangement of arylpropynols and successive radical cyclization with disulfides. Various arylpropynols and disulfides with a number of functional groups are compatible in this reaction that affords the corresponding 2-sulfenylindenones in moderate to good yields.

Distinct epithelial growth factor receptor mutation profile in non-small-cell lung cancer patients from the Xuanwei area of China.

The Xuanwei county in China has a high incidence of lung cancer and related mortality. Previous studies have suggested that these cases may be associated with a distinctive pattern of mutations in the epithelial growth factor receptor (EGFR) gene. In this retrospective study, we investigated the mutation profile of EGFR in non-small-cell lung cancer (NSCLC) tissues from patients in Xuanwei, and the associated clinicopathological characteristics. Specimens from 258 consecutive patients with lung cancer (90 from Xuanwei and 168 from other areas of Yunnan province) were subjected to amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) to detect EGFR mutations. In 67 specimens from Xuanwei, the results were confirmed by direct DNA sequencing for EGFR mutations. Immunohistochemistry (IHC) for the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion protein was performed on all specimens from Xuanwei. We observed that Xuanwei patients presented with distinctive clinicopathological characteristics, including female gender predominance, younger age, higher rate of lymph node metastasis, higher rate of adenocarcinoma histological classification and lower disease stage, and a low rate of the 'classical' mutations on EGFR exons 19 and 21 compared with non-Xuanwei patients (7.8 and 21.6% vs. 49.3 and 39.7%, respectively; P<0.05 for combined data). However, a significantly higher percentage of Xuanwei patients harbored co-mutation of EGFR exons 18 and 20 compared with non-Xuanwei patients (45.1 vs. 4.1%, respectively; P<0.0001). Specimens from 2 Xuanwei patients (2.2%) were positive for the EML4-ALK fusion protein; by IHC, neither harbored EGFR mutations. There was no obvious association between EGFR mutations and disease stage or lymph node involvement. Thus, NSCLC patients in Xuanwei presented with a unique EGFR profile of high rates of co-mutation of exons 18 and 20, and low rates of exon 19 or 21 mutations when compared with patients from other areas in the same province, whereas only few of the tumors from Xuanwei patients expressed the EML4-ALK oncogene.

A full-scale biological treatment system application in the treated wastewater of pharmaceutical industrial park.

A full-scale combined biological system is used for the treatment of treated wastewater discharged from a pharmaceutical industrial park. This treated water is rich in NH(4)(+)-N (average in 86.4 mg/L), low in COD/NH(4)(+)-N (average in 3.4) and low in BOD(5)/COD ratio (average in 0.24) with pH varying from 7.16 to 7.78. The final effluent of the combined treatment process was stably below 100mg/L COD and 20mg/L NH(4)(+)-N, separately, with organic loading rate of 4954 kg COD/d and 92.5 kg NH(4)(+)-N/d. It is found that the BOD(5)/COD ratio could be raised from 0.24 to 0.35, and the production of total VFAs account for 9.57% of the total COD via the treatment of hydrolysis/acidification. MBBR and oxidation ditch represent 35.4% and 60.7% of NH(4)(+)-N removal, 30.2% and 61.5% of COD removal, separately, of the total treatment process. PCR-DGGE is used for microbial community analysis of MBBR and oxidation ditch.