Activating transcription factor 3 is a new biomarker correlation with renal clear cell carcinoma progression.

Background: Clear cell renal cell carcinoma (ccRCC) is the most invasive type of cancer, with a high risk of metastasis and recurrence. Therefore, there is an urgent need to identify novel prognostic predictors and therapeutic targets of ccRCC. Activating transcription factor 3 (ATF3), a tumor oncogene or repressor, has rarely been examined in ccRCC. In the present study, we comprehensively elucidate the prognostic value and potential functions of ATF3 in ccRCC.Methods: Several TCGA-based online databases were used to analyze ATF3 expression in ccRCC and determine ccRCC prognosis. The upstream-binding micro (mi) RNAs of ATF3 and long non-coding (lnc)RNAs were predicted using the StarBase database.Results: Analysis of several TCGA-based online databases showed that ATF3 expression is decreased in ccRCC, suggesting a significant association with the prognosis of patients with ccRCC. Furthermore, we found hsa-miR-221-3p to be potential regulatory miRNA of ATF3 in ccRCC. Prediction and analysis of the upstream lncRNAs indicated that PAXIP1-AS2 and OIP5-AS1 were the most potent upstream lncRNAs of the hsa-miR-221-3p/ATF3 axis in ccRCC. The results of the GO and KEGG analyses implied that ATF3 is likely involved in the regulation of apoptotic signaling in response to endoplasmic reticulum (ER) stress in ccRCC. Correlation analysis revealed a positive relationship between ATF3 expression and ER stress.Conclusions: Our in silico findings highlighted that ATF3 expression was low in ccRCC and negatively correlated with poor prognosis. Furthermore, PAXIP1-AS2 and the OIP5-AS1/hsa-miR-221-3p/ATF3 axis were identified as significant potential regulators of ER stress-mediated apoptosis in ccRCC.

Down-regulation of interleukin-2 predicts poor prognosis and associated with immune escape in lung adenocarcinoma.

Background and Objective: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and has a poor prognosis. Interleukin-2 (IL2) is a cytokine that stimulates lymphocyte proliferation. However, its role in LUAD remains unclear. Methods: The UALCAN, human protein atlas (HPA), and tumor immune estimation resource (TIMER) databases were used to investigate IL2 expression in samples from patients with LUAD. The HPA, PrognoScan, and Kaplan-Meier plotter databases were used to examine the prognostic value of IL2 in LUAD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyze IL2-interacting genes identified through the GeneMANIA database. TIMER was used to analyze the correlation of IL2 expression with immune cell infiltration and immune checkpoint expression levels in LUAD. Results: Bioinformatic analysis using the TIMER, The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and HPA public databases showed that IL2 expression was lower in patients with LUAD than in the normal control group. Moreover, patients with low IL2 expression exhibited poor overall survival. Furthermore, IL2 expression was significantly positively correlated with various immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, in patients with LUAD. Additionally, IL2 expression was markedly positively associated with the above-mentioned immune cells. Furthermore, IL2 expression was positively correlated with PD-1, PD-L1, and CTLA-4 expression. Conclusion: Our results indicate that down-regulation of IL2 predicts poor prognosis and is associated with immune escape in LUAD, and IL2 could serve as a potential novel prognostic biomarker of LUAD.

In vitro susceptibility profiles of Candida parapsilosis species complex subtypes from deep infections to nine antifungal drugs.

Introduction. The Candida parapsilosis complex can be divided into C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis subtypes. It is uncommon for drug sensitivity tests to type them.Gap Statement. In routine susceptibility reports, drug susceptibility of C. parapsilosis complex subtypes is lacking.Aim. The aim of this study is to investigate the antifungal susceptibility and clinical distribution characteristics of the C. parapsilosis complex subtypes causing deep infection in patients.Methodology. Non-repetitive strains of C. parapsilosis complex isolated from deep infection from 2017 to 2019 were collected. Species-level identification was performed using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer and confirmed using ITS gene sequencing, when necessary. Antifungal susceptibility testing was performed using the Sensititre YeastOne system method.Results. A total of 244 cases were included in the study, including 176 males (72.13 %, 60.69±13.43 years) and 68 females (27.87 %, 60.21±10.59 years). The primary diseases were cancer (43.44 %), cardiovascular disease (25.00 %), digestive system diseases, (18.44 %), infection (6.97 %), and nephropathy (6.15 %). Strains were isolated from the bloodstream (63.11 %), central venous catheters (15.16 %), pus (6.56 %), ascites (5.74 %), sterile body fluid (5.33 %), and bronchoalveolar lavage fluid (BALF, 4.09 %). Of the 244 C. parapsilosis complex strains, 179 (73.26 %) were identified as C. parapsilosis sensu stricto, 62 (25.41 %) were C. orthopsilosis, and three (1.23 %) were C. metapsilosis. Only one C. parapsilosis sensu stricto strain was resistant to anidulafungin, micafungin, caspofungin, and voriconazole, and it was non-wild-type (NWT) to amphotericin B. Furthermore, six C. parapsilosis sensu stricto strains were resistant to fluconazole, and one was dose-dependent susceptible. Five C. parapsilosis sensu stricto strains were NWT to posaconazole. Only one C. orthopsilosis strain was NWT for anidulafungin, micafungin, caspofungin, fluconazole, voriconazole, amphotericin B, and posaconazole, while the rest of the strains were wild-type.Conclusion. C. parapsilosis sensu stricto was the main clinical isolate from the C. parapsilosis complex in our hospital. Most strains were isolated from the bloodstream. The susceptibility rate to commonly used antifungal drugs was more than 96 %. Furthermore, most of the infected patients were elderly male cancer patients.

Serum amyloid A (SAA) and Interleukin-6 (IL-6) as the potential biomarkers for gastric cancer.

To explore serum amyloid A (SAA) and interleukin-6 (IL-6) as potential diagnostic biomarkers for gastric cancer (GCa) and the application value of the combined diagnosis of SAA, IL6, and Cancer embryonic antigen. Serum samples were collected before the initial surgery from 159 patients comprising samples from 122 patients with GCa and 37 patients with benign gastric disease. All patients were hospitalized at Beijing Aerospace General Hospital in China between 2018 and 2020. The IL-6 and SAA levels were assessed using standard laboratory protocols. The levels of SAA and IL-6 were significantly higher in patients with GCa than in controls. Compared with the healthy group, the concentration of SAA and IL-6 in FIGO III-IV group were significantly higher and the difference were statistically significant. In addition, significant differences were observed between the FIGO III-IV group and FIGO I-II groups. The Receiver operating characteristic (ROC) curve for the combined detection of SAA, IL-6, and Cancer embryonic antigen showed an area under the curve (AUC) of 0.948, sensitivity of 91.0%, and specificity of 89.2%. Spearman's correlation analysis indicated obvious correlations among the levels of serum SAA, IL-6, advanced FIGO stage, lymphatic invasion, and distant metastasis. AA and IL-6 may serve as useful biomarkers for poor prognosis of GCa. Clinical diagnosis combined with SAA and IL-6 may help assess therapeutic outcomes.

Prevalence of Carbapenem-Resistant Klebsiella pneumoniae Infection in a Northern Province in China: Clinical Characteristics, Drug Resistance, and Geographic Distribution.

PURPOSE: In this study, we analyzed the clinical distribution and drug resistance of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains, the minimum inhibitory concentrations (MIC), MIC50 and MIC90, and geographical distribution in Hebei Province, China. We aimed to provide epidemiological research data, formulate appropriate combined treatment schemes, reasonably select antibiotics, and standardize nosocomial infection control schemes. PATIENTS AND METHODS: A total of 6328 strains of CRKP were collected from 2017 to 2019. The MIC was determined for the drug sensitivity test, and the experimental data were statistically analyzed using WHONET5.6. RESULTS: The detection rate of CRKP increased annually from 13.4% in 2017 to 14.5% in 2018, and 14.6% in 2019. The ratio of males to females was approximately 2:1; 53.6% were elderly, 39% were adults, 4.8% were minors, and 2.5% were newborns. The specimens collected were mainly sputum (70.9%). The resistance rate of CRKP to carbapenems and other ß-lactam antibiotics was found to be increasing, with resistance rates generally greater than 90%. The resistance rate to aminoglycoside antibiotics decreased yearly to approximately 50%, and the resistance rate to quinolones remained unchanged at approximately 80%. From 2017 to 2019, the resistance rate of CRKP in Hebei Province to various antibiotics was high, and the resistance rate to ß-lactam antibiotics increased each year. CONCLUSION: The situation of CRKP resistance is severe in Hebei Province, China. The resistance rate to most antibiotics is very high and shows an upward trend. Among them, the resistance rate to polymyxin is low; however, few resistant strains do exist. MIC50 and MIC90 are higher than their MICs. It mainly causes lung infection in elderly men. This study is helpful to improve the diagnosis, treatment, and prevention of CRKP infection in our province.

Serum amyloid a, a potential biomarker both in serum and tissue, correlates with ovarian cancer progression.

BACKGROUND: Ovarian cancer is the most fatal gynecologic malignancy worldwide due to its vagueness, delay in diagnosis, recurrence, and drug resistance. Therefore, a new type of ovarian cancer treatment prediction biomarker is urgently needed to supplement existing tools. A total of 230 people participated in this study. Out of this figure, 100 participants were patients who underwent an ovarian tumor operation, another 100 participants were ovarian benign patients, and the remaining 30 participants were healthy women. Cancer (experimental) group were 100 patients who underwent ovarian tumor operation, while the control groups were 130 participants consisting of 100 ovarian benign patients and 30 healthy women. Levels of SAA, carbohydrate antigen-125 (CA-125), and human epididymis protein 4 (HE4) were assessed using standard laboratory protocols. A total of 5 ovarian cancer tissues and paracancerous tissues were collected and then stored at - 80 °C until the qRT-PCR assay was conducted. RESULTS: The ROC curve of SAA concentration in ovarian cancer was plotted to obtain the area under the curve AUC = 0.889, the cut-off value 17.05 mg/L, the sensitivity 78.4% and specificity 86.5%. Compared with pretreatment, the level of serum SAA decreased significantly after treatment. The results revealed that there was a significant correlation between the level of serum SAA and advanced FIGO stage, histology subtype, lymphatic invasion, and distant metastasis (p = 0.003,0.002,0.000 and 0.001). The quantitative Reverse transcription polymerase chain reaction (qRT-PCR) assay revealed that the Messenger RNA (mRNA) of SAA-1 and SAA-4 was much higher in cancer tissues than in adjacent tissues, and MMPs was up-regulation including MMP-1, MMP-9 and MMP- 12 in OVCAR-3 cell stimulated by SAA. The transwell assay revealed that SAA could promote OVCAR-3 cell migration. Moreover, SAA can regulate EMT markers and promote AKT pathway activation. CONCLUSIONS: In summary, our results demonstrated that SAA may be a potential diagnosis and treatment prediction biomarker. The SAA promotes OVCAR-3 cell migration by regulating MMPs and EMT which may correlate with AKT pathway activation.

Relationship between Hypoxia and Carcinoembryonic Antigen and Upregulated Carcinoembryonic Antigen is Associated with Poor Prognosis in Breast Cancer Patients.

BACKGROUND: Hypoxia is present in many solid tumors and is a prognostic factor for poor tumorigenesis. Here, we investigated whether carcinoembryonic antigen (CEA) plays a role in the hypoxic microenvironment of breast cancer. METHODS: We researched the expression of CEA in breast tumor tissues and the corresponding paracancerous tissues. Furthermore, western blotting was used to detect the expression levels of CEA in breast cancer cells cultured under hypoxia or normoxia. The expression levels of CEA, hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX (CA-IX) in tumor tissues were detected by immunohistochemical staining. In addition, the correlations between CEA and clinical parameters and prognosis of breast cancer patients were analyzed by statistical analysis. RESULTS: We found that CEA mRNA expression of tissues in breast cancer patients was significantly increased compared to the corresponding paracancerous tissues. Furthermore, the expression levels of CEA in breast cancer cells cultured under hypoxic conditions were elevated compared with those cultured under normoxic conditions. Immunohistochemical staining demonstrated that the expression of CEA in tumor tissues was increased with HIF-1α, and the area of CA-IX expression could be seen with CEA distribution. In addition, the clinical parameter analysis found that serum CEA was significantly associated with malignant clinical features. We also found that elevated CEA expression was related to poor prognosis in breast cancer patients. CONCLUSIONS: CEA expression was elevated in the breast cancer hypoxic microenvironment, and the data suggested a rationale for the use of CEA in breast cancer diagnosis, assessment, and prognosis.

ILF2 cooperates with E2F1 to maintain mitochondrial homeostasis and promote small cell lung cancer progression.

OBJECTIVE: Mitochondria play multifunctional roles in carcinogenesis. Deciphering uncertainties of molecular interactions within mitochondria will promote further understanding of cancer. Interleukin enhancer binding factor 2 (ILF2) is upregulated in several malignancies, however, much remains unknown regarding ILF2 in small cell lung cancer (SCLC). In the current study, we explored ILF2's role in SCLC and demonstrated its importance in mitochondria quality control. METHODS: Colony formation, cell proliferation, cell viability and xenograft studies were performed to examine ILF2's role on SCLC progression. Glucose uptake, lactate production, cellular oxygen consumption rate and extracellular acidification rate were measured to examine the effect of ILF2 on glucose metabolism. RNA-sequencing was utilized to explore genes regulated by ILF2. E2F1 transcriptional activity was determined by dual luciferase reporter assay. Mitochondria quantification and mitochondrial membrane potential assays were performed to examine mitochondrial quality. Gene expression was determined by RT-qPCR, Western blot and IHC assay. RESULTS: ILF2 promotes SCLC tumor growth in vitro and in vivo. ILF2 elevates oxidative phosphorylation expression and declines glucose intake and lactate production. Genome-wide analysis of ILF2 targets identified a cohort of genes regulated by E2F1. In consistent with this, we found ILF2 interacts with E2F1 in SCLC cells. Further studies demonstrated that suppression of E2F1 expression could reverse ILF2-induced tumor growth and enhanced mitochondria function. Significantly, expression of ILF2 is progressively increased during SCLC progression and high ILF2 expression is correlated with higher histologic grades, which indicates ILF2's oncogenic role in SCLC. CONCLUSIONS: Our results demonstrate that ILF2 interacts with E2F1 to maintain mitochondria quality and confers SCLC cells growth advantage in tumorigenesis.

Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer.

BACKGROUND/AIMS: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11's role in NSCLC and the detailed mechanism behind it. METHODS: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial-mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. RESULTS: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial-mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. CONCLUSIONS: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.