Rare presentation of esophageal squamous cell carcinoma with rectal metastasis: A case report.

Esophageal cancer is usually diagnosed at an advanced stage, resulting in poor survival. The common sites of distant metastasis include lung, liver and bones. The present study reports a rare case of esophageal squamous cell carcinoma (SCC) with rectal metastasis. A 65-year-old man was diagnosed with middle thoracic esophageal SCC with multiple lymph node metastasis. The patient achieved good response after chemoradiotherapy and adjuvant chemotherapy. During following up, the computed tomography and magnetic resonance scans showed a mass in front of the rectum with intact mucosa. Biopsies were performed and histopathological findings showed SCC, consistent with metastasis from primary esophageal SCC. The patient subsequently received palliative chemoradiotherapy to the rectal tumour and survived for 5 months. To the best of our knowledge, the present case is the first report of metastatic rectal SCC from the esophagus. It is important to take a biopsy of this unexpected lesion for histological analysis, which can help to discriminate metastatic from primary cancer. The goal of treatment is palliative therapy to improve quality of life and survival for this metastatic disease.

Prognostic nomogram and risk factors for predicting survival in patients with pT2N0M0 esophageal squamous carcinoma.

This study analyzed the impact of factors affecting overall survival in patients with pT2N0M0 esophageal squamous carcinoma (ESCC) and developed a nomogram to predict overall survival (OS). We reviewed the clinical data of 413 patients with pathological T2N0M0 ESCC after radical esophagectomy in two hospitals. Data from one institution was used as the training cohort. A nomogram was established using Cox proportional hazard regression for identifying the prognostic factors affecting for OS in ESCC patients. The area under the curve (AUC), calibration curves and decision curve analysis (DCA) were used to evaluate prognostic efficacy, which was validated in an independent validation cohort. In the training cohort (N = 304), the median OS was 69.33 months, and the 3-, 5- and 10-year OS rates were 76.80%, 67.00% and 56.90%, respectively. The median OS of the validation cohort (N = 109) was 73.50 months, and the 3-, 5- and 10-year OS rates were 77.00%, 67.80% and 55.60%, respectively. According to Cox univariate and multivariate analyses, sex, age, tumor length and the number of resected lymph nodes were identified as predictors of OS. We developed nomograms and performed internal and external validation. The time-dependent receiver operating characteristic (ROC) curve and area under the curve (AUC) value, calibration curve and decision curve analysis (DCA) showed good prediction ability of the nomogram. The developed nomogram can effectively predict OS after esophagectomy in patients with pT2N0M0 ESCC.

Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis.

BACKGROUND: Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal of drug resistance by targeting ferroptosis. The present study aimed to explore the association of fatty acid synthase (FASN) with sorafenib resistance via regulation of ferroptosis and provide a novel treatment strategy to overcome the sorafenib resistance of HCC patients. METHODS: Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Biological information analyses, immunofluorescence assays, western blot assays, and co-immunoprecipitation analyses were conducted to elucidate the functions of FASN in HCC. Both in vitro and in vivo studies were conducted to examine the antitumor effects of the combination of orlistat and sorafenib and CalcuSyn software was used to calculate the combination index. RESULTS: Solute carrier family 7 member 11 (SLC7A11) was found to play an important role in mediating sorafenib resistance. The up-regulation of FASN antagonize of SLC7A11-mediated ferroptosis and thereby promoted sorafenib resistance. Mechanistically, FASN enhanced sorafenib-induced ferroptosis resistance by binding to hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination and proteasomal degradation of HIF1α, and subsequently enhancing transcription of SLC7A11. Orlistat, an inhibitor of FASN, with sorafenib had significant synergistic antitumor effects and reversed sorafenib resistance both in vitro and in vivo. CONCLUSION: Targeting the FASN/HIF1α/SLC7A11 pathway resensitized HCC cells to sorafenib. The combination of orlistat and sorafenib had superior synergistic antitumor effects in sorafenib-resistant HCC cells.

A novel prognostic and therapeutic target biomarker based on complement-related gene signature in gastric cancer.

Background: Gastric cancer (GC) is one of the most prevalent cancer types that reduce human life expectancy. The current tumor-node-metastasis (TNM) staging system is inadequate in identifying higher or lower risk of GC patients because of tumor heterogeneity. Research shows that complement plays a dual role in the tumor development and progression of GC. Methods: We downloaded GC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A complement-related risk signature was constructed through bioinformatics analysis. Subsequently, the predictive ability of this signature was validated with GSE84437 dataset, and a nomogram integrating risk score and common clinical factors was established. Besides, we evaluated the association of risk score with the immune and stromal cell infiltration in TCGA. Furthermore, immunotherapy response prediction and drug susceptibility analysis were conducted to access the ability of the risk signature in predicting the therapeutic effect. Results: A complement-related gene (CRG) signature, based on six genes (SPLG, C9, ITIH1, ZFPM2, CD36, and SERPINE1), was established. In both the training and validation sets, the overall survival of GC patients in the high-risk group was lower than that of the low-risk group, and the nomogram to predict the 1-, 2-, and 3-year survival rates of GC patients was developed. In addition, CIBERSORT algorithm showed the high-risk patients had higher levels of immune cell infiltration than low-risk patients, and the ESTIMATE results implied that the high-risk group had more stromal component in tumor microenvironment. Besides, compared to the low-risk group, there were higher expressions of most immune checkpoint genes and HLA genes in the high-risk group, and the high-risk patients showed higher sensitivity to the chemotherapy and targeted drugs (axitinib, dasatinib, pazopanib, saracatinib, sunitinib and temsirolimus). Conclusions: The novel CRG signature may act as a reliable, efficient tool for prognostic prediction and treatment guidance in future clinical practice.

Patterns of care and prognostic evaluation for stage I-III upper esophageal squamous cell carcinoma: a population-based study.

Background: There is no strong evidence regarding the optimal treatment and specific prognosis prediction model for upper esophageal squamous cell carcinoma (UESCC). This study aimed to investigate the real-world treatment patterns and develop models to predict overall survival (OS) and esophageal cancer-specific survival (ECSS) in patients with stage I-III UESCC. Methods: Patients with T1-4N0-3M0 UESCC in the Surveillance, Epidemiology, and End Results (SEER) database were identified from 2010 to 2017, and randomized to a training cohort and a validation cohort. The effect of treatment patterns on survival were comprehensively analyzed. Nomograms were developed by incorporating independent prognostic factors analyzed by Cox regression in the training cohort and evaluated by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA) in two cohorts. Results: A total of 677 patients were identified, including 452 in the training cohort and 225 in the validation cohort. Among all populations, 71.9% (487) received chemoradiotherapy without surgery, and chemoradiotherapy or/and surgery showed better survival than other treatments. However, surgery was rarely carried out for patients with stage II-III. T stage, N stage, surgery, chemotherapy, and radiotherapy were independent risks for both OS and ECSS, while age was also an independent risk for OS. The C-indexes for nomograms to predict OS (0.71 and 0.72) and ECSS (0.70 and 0.73) were greater than 7th AJCC staging system to predict OS (0.61 and 0.64) and ECSS (0.64 and 0.64) in both the training cohort and the validation cohort. Time-dependent ROC curves and DCA also suggested that nomograms performed consistently better than 7th AJCC staging system. The calibration curves demonstrated good consistency in predicting survival. Conclusions: Chemoradiotherapy was a major treatment with preferable survival for patients with stage I-III UESCC. We have firstly developed and validated prognostic nomograms in patients with stage I-III UESCC, which would play a supplementary role in the current staging system.

Uterine decidual stromal cell-derived exosomes mediate the indirect effects of 1-nitropyrene on trophoblast biological behaviors.

1-nitropyrene (1-NP) is representative nitropolycyclic aromatic hydrocarbon pollutant widely present in exhaust particles of internal combustion engine, which is known for its carcinogenicity and mutagenicity. Previous studies have demonstrated that 1-NP has reproductive toxicity, but the specific mechanism is unknown. In this study, Human decidual stromal cells (HDSCs) were treated by 1-NP, exosomes were extracted from the conditioned medium of HDSCs, which were then used to treat human chorionic trophoblast cells (HTR8/SVneo) for 24 h. The findings showed that human decidual stromal cell-derived exosomes (HDSC-EXOs) can promote the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT; Vimentin and N-cadherin) of HTR8/SVneo by about 64%, 17%, 23%, 81% and 13%. The process of regulating the biological behaviors of embryonic trophoblast cells by maternal decidual stromal cells during pregnancy was simulated. Further investigations showed that HDSC-EXOs treatment activated the Wnt/ß-catenin signaling pathway in HTR8/SVneo. Co-treatment by dickkopf-1 (DKK-1) significantly suppressed the activation of Wnt/ß-catenin signaling pathway in HTR8/SVneo, and inhibited the proliferation, migration, invasion and EMT (N-cadherin and E-cadherin) of HTR8/SVneo by about 60%, 22%, 42%, 25%, 55% and 21%. These findings indicated that 1-NP exposure could induce the secretion of HDSC-EXOs from HDSCs, which in turn activate the Wnt/ß-catenin signaling pathway and enhance the proliferation, migration, invasion and EMT of HTR8/SVneo.

Integrated Analysis and Validation of Autophagy-Related Genes and Immune Infiltration in Acute Myocardial Infarction.

Background: Acute myocardial infarction (AMI) is one of the most critical conditions of coronary heart disease with many uncertainties regarding reduction of ischemia/reperfusion injury, medical treatment strategies, and other aspects. The inflammatory immune response has a bidirectional regulatory role in AMI and plays an essential role in myocardial remodeling after AMI. The purpose of our research was tantamount to explore possible mechanisms of AMI and to analyze the relationship with the immune microenvironment. Methods: We firstly analyzed the expression profile of GSE61144 and HADb to identify differentially expressed autophagy-related genes (DEARGs). Then, we performed GO, functional enrichment analysis, and constructed PPI network by Metascape. A lncRNA-miRNA-mRNA ceRNA network was built, and hub genes were extracted by Cytoscape. After that, we used CIBERSORT algorithm to estimate the proportion of immunocytes, followed by correlation analysis to find relationships between hub DEARGs and immunocyte subsets. Finally, we verified those hub genes in another dataset and cellular experiments qPCR. Results: Compared with controls, we identified 44 DEARGs and then filtered the genes of MCODE by constructing PPI network for further analysis. A total of 45 lncRNAs, 24 miRNAs, 19 mRNAs, 162 lncRNA-miRNA pairs, and 37 mRNA-miRNA pairs were used to construct a ceRNA network, and 4 hub DEARGs (BCL2, MAPK1, RAF1, and PRKAR1A) were extracted. We then estimated 5 classes of immunocytes that differed between AMI and controls. According to the results of correlation analysis, these 4 hub DEARGs may play modulatory effects in immune infiltrating cells, notably in CD8+ T cells and neutrophils. Finally, the same results were verified in GSE60993 and qPCR experiments. Conclusion: Our findings suggest that those hub DEARGs (BCL2, MAPK1, RAF1, and PRKAR1A) and immunocytes probably play functions in the progression of AMI, providing potential diagnostic markers and new perspectives for treatment of AMI.

Impact of examined lymph node number on lymph node status and prognosis in FIGO stage IB-IIA cervical squamous cell carcinoma: A population-based study.

Objective: We aimed to investigate the association of examined lymph node (ELN) number with lymph node status and long-term survival in FIGO stage IB-IIA cervical squamous cell carcinoma(CSCC) and to determine the minimum number of ELN associated with survival improvement. Method: Data from the Surveillance, Epidemiology, and End Results Program (SEER) database of FIGO stage IB-IIA CSCC patients undergoing hysterectomy and pelvic lymphadenectomy in 2004-2016 were analyzed to explore the relationship between ELN number and lymph node status and overall survival (OS) by using the multivariable approach. The estimated probability of falsely identifying a patient as node-negative and the hazard ratios (HRs) for each ELN was fitted with a LOWESS smoother, and the structural breakpoints were determined. X-tile software was used to determine the optimal cutoff value for ELNs. Results: A total of 2627 patients were analyzed. The optimal cutoff value of the ELN number was identified as 7 based on the results of X-tile software. The structural breakpoints according to the associations between the number of ELNs and the estimated risk of false-negative lymph node dissection and HRs for overall survival were 9 and 8, respectively. The multivariate analysis indicated that ELN number was an independent prognostic factor for OS, both as a continuous or categorical variable. To further explore the effect of more ELNs on survival, another cutoff value of 17 was chosen to compare the survival curves of patients. The multivariate-adjusted COX model showed that patients with ELN<8 had a significantly higher risk of death than those with ELN8-17 (HR=1.447, 95% CI =1.075-1.947, p=0.015), but there was no significant difference in overall survival between patients with ELN>17 and patients with ELN8-17 (HR=0.822, 95%CI =0.665-1.016, p=0.070). Conclusion: A sufficient number of ELNs was associated with better long-term survival in FIGO stage IB-IIA CSCC. At least 8 ELNs need to be examined for prognostic stratification. Excessive lymph node dissection (ELN>17) may not confer additional survival benefits.

MiR-582-3p participates in the regulation of biological behaviors of A549 cells by ambient PM2.5 exposure.

Ambient fine particulate matter (PM2.5) is one of the main environmental air pollutants that is closely related to the development of lung cancer, but the mechanisms are unclear. In this study, A549 cells were exposed to ambient PM2.5 to investigate the alterations of biological behaviors, and the possible role of miR-582-3p in the effects was further explored. The findings showed that PM2.5 exposure could significantly enhance the biological behaviors of A549 cells, and promote their epithelial-mesenchymal transition (EMT) transformation, especially at relatively low doses. Over-activation of Wnt/ß-catenin signaling pathway and increased expression of miR-582-3p were also found in A549 cells after PM2.5 exposure. After the knockdown of miR-582-3p in A549 cells, the effects of PM2.5 on malignant biological behavior changes, EMT, and the activation of Wnt/ß-catenin signaling pathway were all significantly alleviated. Furthermore, the inhibition of Wnt/ß-catenin signaling pathway also inhibited the EMT process of A549 cells, which was rescued by the overexpression of miR-582-3p. Therefore, this study showed that ambient PM2.5 can upregulate the expression of miR-582-3p, consequently activate the Wnt/ß-catenin signaling pathway, and thereby enhance EMT transformation and promote the malignant biological behaviors of A549 cells. These findings provide evidence for further research into the mechanisms by which exposure to PM2.5 in the environment promotes lung cancer.

Computed Tomography-Based Radiomics in Predicting T Stage and Length of Esophageal Squamous Cell Carcinoma.

BACKGROUND: Because of the superficial and infiltrative spreading patterns of esophageal squamous cell carcinoma (ESCC), an accurate assessment of tumor extent is challenging using imaging-based clinical staging. Radiomics features extracted from pretreatment computed tomography (CT) or magnetic resonance imaging have shown promise in identifying tumor characteristics. Accurate staging is essential for planning cancer treatment, especially for deciding whether to offer surgery or radiotherapy (chemotherapy) in patients with locally advanced ESCC. Thus, this study aimed to evaluate the predictive potential of contrast-enhanced CT-based radiomics as a non-invasive approach for estimating pathological tumor extent in ESCC patients. METHODS: Patients who underwent esophagectomy between October 2011 and September 2017 were retrospectively studied and included 116 patients with pathologically confirmed ESCC. Contrast-enhanced CT from the neck to the abdomen was performed in all patients during the 2 weeks before the operation. Radiomics features were extracted from segmentations, which were contoured by radiologists. Cluster analysis was performed to obtain clusters with similar radiomics characteristics, and chi-squared tests were used to assess differences in clinicopathological features and survival among clusters. Furthermore, a least absolute shrinkage and selection operator was performed to select radiomics features and construct a radiomics model. Receiver operating characteristic analysis was used to evaluate the predictive ability of the radiomics signatures. RESULTS: All 116 ESCC patients were divided into two groups according to the cluster analysis. The chi-squared test showed that cluster-based radiomics features were significantly correlated with T stage (p = 0.0254) and tumor length (p = 0.0002). Furthermore, CT radiomics signatures exhibited favorable predictive performance for T stage (area under the curve [AUC] = 0.86, sensitivity = 0.77, and specificity = 0.87) and tumor length (AUC = 0.95, sensitivity = 0.92, and specificity = 0.91). CONCLUSIONS: CT contrast radiomics is a simple and non-invasive method that shows promise for predicting pathological T stage and tumor length preoperatively in ESCC patients and may aid in the accurate assessments of patients in combination with the existing examinations.

Combining Fiber Enzymatic Pretreatments and Coupling Agents to Improve Physical and Mechanical Properties of Hemp Hurd/Wood/Polypropylene Composite.

Natural fiber/plastic composites combine the low density and excellent mechanical properties of the natural fiber with the flexibility and moisture resistance of the plastic to create materials tailored to specific applications in theory. Wood/plastic composites (WPC) are the most common products, but many other fibers are being explored for this purpose. Among the more common is hemp hurd. Natural fibers are hydrophilic materials and plastics are hydrophobic, therefore one problem with all of these products is the limited ability of the fiber to interact with the plastic to create a true composite. Thus, compatibilizers are often added to enhance interactions, but fiber pretreatments may also help improve compatibility. The effects of pectinase or cellulase pretreatment of wood/hemp fiber mixtures in combination with coupling agents were evaluated in polypropylene panels. Pretreatments with pectinase or cellulase were associated with reduced thickness swell (TS24h) as well as increased modulus of rupture and modulus of elasticity. Incorporation of 5.0% silane or 2.5% silane/2.5% titanate as a coupling agent further improved pectinase-treated panel properties, but was associated with diminished properties in cellulase treated fibers. Combinations of enzymatic pretreatment and coupling agents enhanced fiber/plastic interactions and improved flexural properties, but the effects varied with the enzyme or coupling agent employed. The results illustrate the potential for enhancing fiber/plastic interactions to produce improved composites.

Early Prediction of Left Ventricular Reverse Remodeling in First-Diagnosed Idiopathic Dilated Cardiomyopathy: A Comparison of Linear Model, Random Forest, and Extreme Gradient Boosting.

Introduction: Left ventricular reverse remodeling (LVRR) is associated with decreased cardiovascular mortality and improved cardiac survival and also crucial for therapeutic options. However, there is a lack of an early prediction model of LVRR in first-diagnosed dilated cardiomyopathy. Methods: This single-center study included 104 patients with idiopathic DCM. We defined LVRR as an absolute increase in left ventricular ejection fraction (LVEF) from >10% to a final value >35% and a decrease in left ventricular end-diastolic diameter (LVDd) >10%. Analysis features included demographic characteristics, comorbidities, physical sign, biochemistry data, echocardiography, electrocardiogram, Holter monitoring, and medication. Logistic regression, random forests, and extreme gradient boosting (XGBoost) were, respectively, implemented in a 10-fold cross-validated model to discriminate LVRR and non-LVRR, with receiver operating characteristic (ROC) curves and calibration plot for performance evaluation. Results: LVRR occurred in 47 (45.2%) patients after optimal medical treatment. Cystatin C, right ventricular end-diastolic dimension, high-density lipoprotein cholesterol (HDL-C), left atrial dimension, left ventricular posterior wall dimension, systolic blood pressure, severe mitral regurgitation, eGFR, and NYHA classification were included in XGBoost, which reached higher AU-ROC compared with logistic regression (AU-ROC, 0.8205 vs. 0.5909, p = 0.0119). Ablation analysis revealed that cystatin C, right ventricular end-diastolic dimension, and HDL-C made the largest contributions to the model. Conclusion: Tree-based models like XGBoost were able to early differentiate LVRR and non-LVRR in patients with first-diagnosed DCM before drug therapy, facilitating disease management and invasive therapy selection. A multicenter prospective study is necessary for further validation. Clinical Trial Registration:http://www.chictr.org.cn/usercenter.aspx (ChiCTR2000034128).

Mapping of Cervical and Upper Mediastinal Lymph Node Recurrence for Guiding Clinical Target Delineation of Postoperative Radiotherapy in Thoracic Esophageal Squamous Cell Carcinoma.

BACKGROUND: The lower neck and upper mediastinum are the major regions for postoperative radiotherapy (PORT) in thoracic esophageal squamous cell carcinoma (TESCC). However, there is no uniform standard regarding the delineation of nodal clinical target volume (CTVnd). This study aimed to map the recurrent lymph nodes in the cervical and upper mediastinal regions and explore a reasonable CTVnd for PORT in TESCC. METHODS: We retrospectively reviewed patients in our hospital with first cervical and/or upper mediastinal lymph node recurrence (LNR) after upfront esophagectomy. All of these recurrent lymph nodes were plotted on template computed tomography (CT) images with reference to surrounding structures. The recurrence frequency at different stations was investigated and the anatomic distribution of recurrent lymph nodes was analyzed. RESULTS: A total of 119 patients with 215 recurrent lymph nodes were identified. There were 47 (39.5%) patients with cervical LNR and 102 (85.7%) patients with upper mediastinal LNR. The high-risk regions were station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. LNR in the external group of station 104L/R was not common, and LNR was not found in the narrow spaces where the trachea was in close contact with the innominate artery, aortic arch and mediastinal pleura. LNR below the level of the cephalic margin of the superior vena cava was also not common for upper TESCC. CONCLUSIONS: The CTVnd of PORT in the cervical and upper mediastinal regions should cover station 101L/R, station 104L/R, station 106recL/R, station 105 and station 106pre for upper TESCC and station 104L/R, station 106recL/R, station 105, station 106pre and station 106tbL for middle and lower TESCCs. Based on our results, we proposed a useful atlas for guiding the delineation of CTVnd in TESCC.

Prognostic value of inflammation-based indices in patients with resected hepatocellular carcinoma.

BACKGROUND: As is well recognized that inflammation plays a crucial role in the genesis and progression of various cancer. Here we investigate the prognostic value of a novel index: the combination of neutrophil to lymphocyte ratio and platelet distribution width (coNLR-PDW) in post-operation patients with resectable hepatocellular carcinoma (HCC). METHODS: The receiver operating characteristic (ROC) curve was utilized to determine the optimal cutoff values of continuous variables, including the neutrophil-lymphocyte ratio (NLR) and platelet distribution width (PDW). Kaplan-Meier method and the Log-rank test were used to compare survival differences across three groups stratified by the coNLR-PDW score. Univariate and multivariate Cox proportional hazard regression analyses were adopted to identify independent factors of HCC patient's prognosis. RESULTS: 1.59 and 13.0 were perceived as the optimal cutoff value for NLR and PDW based on the ROC curve, respectively. Kaplan-Meier method revealed that a higher coNLR-PDW score predicts poorer overall survival (OS) and disease-free survival (DFS) (P < 0.001). coNLR-PDW was demonstrated as an independent factor for both OS and DFS using Cox regression analysis in training and validation cohort. CONCLUSION: coNLR-PDW is recognized as a valuable biomarker for predicting the survival of patients with HCC.

Diagnostic Value of Serum D-Dimer for Detection of Gallbladder Carcinoma.

BACKGROUND: Previous studies have shown that D-dimer plays an essential role in the occurrence and development of various tumors, and its diagnostic value in gallbladder carcinoma (GBC) is unknown. Therefore, the purpose of our study was to explore the diagnostic value of D-dimer in distinguishing between gallbladder carcinoma and benign controls. METHODS: We retrospectively included age and gender-matched patients with gallbladder carcinoma and benign gallbladder lesions, and analyzed the diagnostic value of inflammatory markers, D-dimers, and tumor biomarkers by receiver operating characteristic curves (ROC). RESULTS: The area under the ROC curve of white blood cells (WBC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), D-dimer, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) were 0.600, 0.760, 0.729, 0.849, 0.502, 0.699, and 0.802, respectively. The combined diagnostic value of D-dimer and CA19-9 was 0.920, which was superior to other joint indicators. CONCLUSION: Serum D-dimer may be considered as a potential biomarker for detection of GBC. Moreover, the combined diagnosis of D-dimer and CA19-9 has excellent diagnostic value in gallbladder carcinoma.

Combination of Sodium Cantharidinate with Cisplatin Synergistically Hampers Growth of Cervical Cancer.

BACKGROUND: Sodium cantharidinate (SC) has been broadly applied in lung cancer treatment in China, while its specific function in cervical cancer (CC), a great contributor to death of female reproductive system cancers, remains unclear. Our research evaluated the anti-tumor effects of SC in CC and the mechanism involved. METHODS: First, cisplatin (DDP)-resistant Caski-1 and ME180 cell lines were developed and treated with SC. The effects of SC on CC cell growth were then evaluated. Subsequently, the genes targeted by SC were predicted via the bioinformatics website. The correlations between PTPN1 expression and tumor stage, lymph node metastasis and tumor differentiation were examined. We further conducted rescue experiments by overexpressing PTPN1 in CC cells, followed by SC and cisplatin treatments. The activation of the PI3K/AKT pathway in CC cells, and the effect of SC on the growth and drug resistance of Caski-1 cells in vivo were investigated. RESULTS: The sensitivity of Caski-1 and ME180 cells to DDP was increased after SC treatment, which also enhanced the inhibitory effect of DDP on the cell growth. By prediction, we found that SC could target PTPN1. Patients with high expression of PTPN1 had higher clinical stage, lymph node metastasis and lower tumor differentiation. SC inhibited PTPN1 expression. Overexpression of PTPN1 attenuated the effect of SC. Furthermore, PTPN1 activated the PI3K/AKT pathway. Moreover, SC treatment inhibited the growth and drug resistance of Caski-1 cells in vivo. CONCLUSION: SC promotes drug sensitivity of CC cells to DDP by targeting PTPN1, thereby impairing the PI3K/AKT pathway.

LMNB2 is a prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma.

BACKGROUND: Previous studies have suggested Lamin B2 (LMNB2) as an oncogene in lung cancer. However, the role of LMNB2 in hepatocellular carcinoma (HCC) remains unclear. METHOD: The expression of LMNB2 was compared between HCC samples and non-tumor samples in multiple datasets. In addition, the prognostic value of LMNB2 in HCC was also investigated. Furthermore, the cBioPortal was utilized to analyze the genomic alternation of LMNB2 in HCC. Besides, co-expression genes and functional enrichment analysis were evaluated using LinkedOmics to determine the function of LMNB2. Finally, the correlation between LMNB2 and immune infiltration was assessed using Tumor Immune Estimation Resource (TIMER). RESULTS: Elevated LMNB2 expression level was identified in HCC patients in multiple datasets. Moreover, increased levels of LMNB2 were associated with poor overall survival (OS) and disease-free survival (DFS). The functional enrichment analysis revealed that LMNB2 plays an essential role via the cell cycle pathway, spliceosome, hippo-signaling pathway, and metabolic pathways. Besides, copy number variation (CNV) and methylation were significantly associated with LMNB2 expression. Additionally, increased levels of LMNB2 were significantly associated with B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. CONCLUSION: LMNB2 is a potential HCC prognostic and diagnostic biomarker.

Identifying Long Non-coding RNA of Prostate Cancer Associated With Radioresponse by Comprehensive Bioinformatics Analysis.

Although radiotherapy is greatly successful in the treatment of prostate cancer (PCa), radioresistance is still a major challenge in the treatment. To our knowledge, this study is the first to screen long non-coding RNAs (lncRNAs) associated with radioresponse in PCa by The Cancer Genome Atlas (TCGA). Bioinformatics methods were used to identify the differentially expressed lncRNAs and protein-coding genes (PCGs) between complete response (CR) and non-complete response (non-CR) groups in radiotherapy. Statistical methods were applied to identify the correlation between lncRNAs and radioresponse as well as lncRNAs and PCGs. The correlation between PCGs and radioresponse was analyzed using weighted gene co-expression network analysis (WGCNA). The three online databases were used to predict the potential target miRNAs of lncRNAs and the miRNAs that might regulate PCGs. RT-qPCR was utilized to detect the expression of lncRNAs and PCGs in our PCa patients. A total of 65 differentially expressed lncRNAs and 468 differentially expressed PCGs were found between the two groups of PCa. After the chi-square test, LINC01600 was selected to be highly correlated with radioresponse from the 65 differentially expressed lncRNAs. Pearson correlation analysis found 558 PCGs co-expressed with LINC01600. WGCNA identified the darkred module associated with radioresponse in PCa. After taking the intersection of the darkred module of WGCNA, differentially expressed PCGs between the two groups of PCa, and the PCGs co-expressed with LINC01600, three PCGs, that is, JUND, ZFP36, and ATF3 were identified as the potential target PCGs of LINC01600. More importantly, we detected the expression of LINC01600 and three PCGs using our PCa patients, and finally verified that LINC01600 and JUND were differentially expressed between CR and non-CR groups, excluding ZFP36 and ATF3. Meantime, the potential regulation ability of LINC01600 for JUND in PCa cell lines was initially explored. In addition, we constructed the competing endogenous RNA (ceRNA) network of LINC01600-miRNA-JUND. In conclusion, we initially reveal the association of LINC01600 with radioresponse in PCa and identify its potential target PCGs for further basic and clinical research.

Diagnostic value of HOX transcript antisense RNA for cancer detection: a meta-analysis.

Aim: Numerous studies have investigated the diagnostic role of long noncoding RNA HOX transcript antisense RNA in cancers, but its diagnostic efficacy is inconsistent. Methods: The PubMed, Embase, Web of Science and Cochrane Library databases are used to retrieve relevant studies. The bivariate effect model was used to compute the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the receiver operating characteristic curve. Results: A total of 13 studies were included in this meta-analysis. The combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the receiver operating characteristic curve were: 0.77, 0.83, 4.7, 0.28, 17 and 0.87, respectively. Deeks' funnel plot test (p = 0.103) indicated no publication bias. Conclusion: Long noncoding RNA HOX transcript antisense RNA may be a useful biomarker for cancer detection.

Prognostic value of microRNA-451 in various cancers: A meta-analysis.

BACKGROUND: Increasing evidence shows microRNA-451 plays a crucial role in various tumors, but there is inconsistency. The aim of this study was to explore the prognostic role of miR-451 in various tumors. METHODS: Online PubMed, EMBASE, Web of Science, and the Cochrane library database were searched through February 2019. Hazard ratios (HRs) were extracted and used to describe the association between expression of microRNA-451 and survival outcome, and the correlation between microRNA-451 and clinicopathologic features were described by pooled odds ratios (ORs). RESULTS: Sixteen retrospective studies containing 2122 patients were incorporated in this meta-analysis. High expression of miR-451 was considered statistically associated with prolonged overall survival (OS) (HR = 0.62, 95% CI 0.49-0.80, p < 0.001) as well as RFS/DFS (HR = 0.55, 95% CI 0.42-0.71, p < 0.001) compared with low expression of miR-451. Besides, the pooled ORs revealed significant association between high expression of miR-451 with lymph node invasion (yes vs. no) (OR = 0.64, 95% CI 0.46-0.90, P = 0.01), tumor diameter (big vs. small) (OR = 0.77, 95% CI 0.60-0.97, P = 0.028) and tumor stage (III + IV vs. I + II) (OR = 0.62, 95% CI 0.42-0.93, P = 0.019). CONCLUSION: MicroRNA-451 may serve as a promising clinical prognostic biomarker in various carcinomas.