scholarly journals CLDN15 is a novel diagnostic marker for malignant pleural mesothelioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masayuki Watanabe ◽  
Tomohito Higashi ◽  
Kana Ozeki ◽  
Atsuko Y. Higashi ◽  
Kotaro Sugimoto ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Survival Rate ◽  
Lung Adenocarcinoma ◽  
Clinical Setting ◽  
Diagnostic Marker ◽  
Pleural Mesothelioma ◽  
Poor Survival ◽  
False Negatives ◽  
Tissue Samples ◽  
Positive Ratio

AbstractMalignant mesothelioma is a cancer with a poor survival rate. It is difficult to diagnose mesotheliomas because they show a variety of histological patterns similar to those of various other cancers. However, since currently used positive markers for mesotheliomas may show false positives or false negatives, a novel mesothelial positive marker is required. In the present study, we screened 25 claudins and found that claudin-15 is expressed in the mesothelial cells. We made new rat anti-human claudin-15 (CLDN15) monoclonal antibodies that selectively recognize CLDN15, and investigated whether CLDN15 is a good positive marker for malignant pleural mesotheliomas (MPMs) using MPM tissue samples by immunohistochemistry and semi-quantification of the expression level using an immunoreactive score (IRS) method. Of 42 MPM samples, 83% were positive for CLDN15. The positive ratio was equal to or greater than other positive markers for MPMs including calretinin (81%), WT-1 (50%), and D2-40 (81%). In 50 lung adenocarcinoma sections, four cases were positive for CLDN15 and the specificity (92%) was comparable with other markers (90–100%). Notably, CLDN15 was rarely detected in 24 non-mesothelial tumors in the tissue microarray (12/327 cases). In conclusion, CLDN15 can be used in the clinical setting as a positive marker for MPM diagnosis.

Total ankle replacement: is pre-operative varus deformity a predictor of poor survival rate and clinical and radiological outcomes?

2018 ◽  
Vol 43 (1) ◽  
pp. 243-249 ◽  
Author(s):  
Federico Giuseppe Usuelli ◽  
Claudia Angela Di Silvestri ◽  
Riccardo D’Ambrosi ◽  
Annalisa Orenti ◽  
Filippo Randelli
Keyword(s):  
Survival Rate ◽  
Varus Deformity ◽  
Total Ankle Replacement ◽  
Poor Survival ◽  
Ankle Replacement

scholarly journals Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10470
Author(s):  
Wanzhen Li ◽  
Shiqing Liu ◽  
Shihong Su ◽  
Yang Chen ◽  
Gengyun Sun
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Target Genes ◽  
Predictive Accuracy ◽  
Differentially Expressed ◽  
Prognostic Signature ◽  
Tissue Samples ◽  
Gene Set ◽  
Differentially Expressed Mirnas

MicroRNA (miRNA, miR) has been reported to be highly implicated in a wide range of biological processes in lung cancer (LC), and identification of differentially expressed miRNAs between normal and LC samples has been widely used in the discovery of prognostic factors for overall survival (OS) and response to therapy. The present study was designed to develop and evaluate a miRNA-based signature with prognostic value for the OS of lung adenocarcinoma (LUAD), a common histologic subtype of LC. In brief, the miRNA expression profiles and clinicopathological factors of 499 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. Kaplan–Meier (K-M) survival analysis showed significant correlations between differentially expressed miRNAs and LUAD survival outcomes. Afterward, 1,000 resample LUAD training matrices based on the training set was applied to identify the potential prognostic miRNAs. The least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to constructed a six-miRNA based prognostic signature for LUAD patients. Samples with different risk scores displayed distinct OS in K-M analysis, indicating considerable predictive accuracy of this signature in both training and validation sets. Furthermore, time-dependent receiver operating characteristic (ROC) analysis demonstrated the nomogram achieved higher predictive accuracy than any other clinical variables after incorporating the clinical information (age, sex, stage, and recurrence). In the stratification analysis, the prognostic value of this classifier in LUAD patients was validated to be independent of other clinicopathological variables, such as age, gender, tumor recurrence, and early stage. Gene set annotation analyses were also conducted through the Hallmark gene set and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating target genes of the six miRNAs were positively related to various molecular pathways of cancer, such as hallmark UV response, Wnt signaling pathway and mTOR signaling pathway. In addition, fresh cancer tissue samples and matched adjacent tissue samples from 12 LUAD patients were collected to verify the expression of miR-582’s target genes in the model, further revealing the potential relationship between SOX9, RASA1, CEP55, MAP4K4 and LUAD tumorigenesis, and validating the predictive value of the model. Taken together, the present study identified a robust signature for the OS prediction of LUAD patients, which could potentially aid in the individualized selection of therapeutic approaches for LUAD patients.

scholarly journals UBE2V2 promotes metastasis by regulating EMT and predicts a poor prognosis in lung adenocarcinoma.

2021 ◽  
Author(s):  
Zheng Yang ◽  
Qiang Xue ◽  
Caishen Du ◽  
Miaosen Zhen ◽  
Jianxun Xu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Patient Survival ◽  
Immunohistochemical Analysis ◽  
S Phase ◽  
Clinicopathological Factors ◽  
Migration Ability ◽  
Survival Prognosis ◽  
Tissue Samples ◽  
Normal Tissues ◽  
Ubiquitin Conjugating Enzymes

Abstract Background: Belonging to the ubiquitin-conjugating enzymes (E2s) family, UBE2V2 demonstrated a remarkable tumourigenic ability in many kinds of cancers. However, the interrelationship between UBE2V2 expression and morbidity of lung adenocarcinoma (LUAD) is still unknown. Methods: By using TCGA predictions and clinical tissue samples, we assessed the expression of UBE2V2 mRNA and protein in LUAD and analyzed its relationship with different clinicopathological factors as well as survival prognosis. Besides, we further studied the EMT signaling pathway that promotes LUAD metastasis and other phenotypic experiments by using lentivirus to transfect LUAD cells. Results: Our research results showed that compared with normal tissues, the expression of UBE2V2 mRNA and protein in LUAD was significantly increased (P<0.001). UBE2V2 might be considered as an independent prognostic molecule for LUAD patient survival prognosis based on TCGA prediction (HR:1.497 P=0.012) and immunohistochemical analysis (ICH) (HR:1.842 P=0.042). ICH showed that UBE2V2 was related to the following clinicopathological factors, including gender (P=0.021), stage (P=0.042), lymph node metastasis (P=0.021) and differentiated degree (P=0.015). Finally, knockdown of UBE2V2 significantly reduced the migration ability by regulating the EMT pathway. The knockdown of UBE2V2 inhibited cells proliferation, reduced the proportion of cells in S phase and promoted cell apoptosis. Interestingly, UBE2V2 expression is negatively correlated with B cells, CD4 + T cells, macrophages and dendritic cells. Conclusions: In summary, UBE2V2 might play an important role in the progression of LUAD.

Prognostic phenotypes of early-stage lung adenocarcinoma

2021 ◽  
pp. 2101674
Author(s):  
Anne-Sophie Lamort ◽  
Jan Christian Kaiser ◽  
Mario A.A. Pepe ◽  
Ioannis Lilis ◽  
Giannoula Ntaliarda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Early Stage ◽  
Machine Learning Algorithms ◽  
Prognostic Information ◽  
Tissue Samples ◽  
Cancer Hallmarks ◽  
Patient Subgroups ◽  
Prognostic Power

BackgroundSurvival after curative resection of early-stage lung adenocarcinoma (LUAD) varies and prognostic biomarkers are urgently needed.MethodsLarge-format tissue samples from a prospective cohort of 200 patients with resected LUAD were immunophenotyped for cancer hallmarks TP53, NF1, CD45, PD-1, PCNA, TUNEL, and FVIII, and were followed for median (95%CI)=2.34 (1.71–3.49) years.ResultsUnsupervised hierarchical clustering revealed two patient subgroups with similar clinicopathologic features and genotype, but with markedly different survival: “proliferative” patients (60%) with elevated TP53, NF1, CD45, and PCNA expression had 50% 5-year overall survival while “apoptotic” patients (40%) with high TUNEL had 70% 5-year survival [HR95%CI=2.23 (1.33–3.80); p=0.0069]. Cox regression and machine learning algorithms including random forests built clinically useful models: a score to predict overall survival and a formula and nomogram to predict tumour phenotype. The distinct LUAD phenotypes were validated in TCGA and KMplotter data and showed prognostic power supplementary to IASLC TNM stage and WHO histologic classification.ConclusionsTwo molecular subtypes of LUAD exist and their identification provides important prognostic information.

Prognosis-Related Autophagy Genes in Female Lung Adenocarcinoma

2020 ◽  
Author(s):  
Zhongxiang Liu ◽  
Haicheng Tang ◽  
Yongqian Jiang ◽  
Xiaopeng Zhan ◽  
Sheng Kang ◽  
...  
Keyword(s):  
Survival Rate ◽  
Lung Adenocarcinoma ◽  
Regression Model ◽  
Clinical Data ◽  
Risk Score ◽  
Risk Group ◽  
Risk Scores ◽  
Clinicopathological Parameters ◽  
Significant Difference ◽  
Cox Analysis

Abstract Background: To screen the prognosis-related autophagy genes of female lung adenocarcinoma by the transcriptome data and clinical data from TCGA database.Methods: In this study, Screen meaningful female lung adenocarcinoma differential genes in TCGA, use univariate COX proportional regression model to select genes related to prognosis, and establish the best risk model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied for carrying out bioinformatics analysis of gene function.Results: The gene expression and clinical data of 260 female lung adenocarcinoma patient samples were downloaded from TCGA. 12 down-regulated genes: NRG3, DLC1, NLRC4, DAPK2, HSPB8, PPP1R15A, FOS, NRG1, PRKCQ, GRID1, MAP1LC3C, GABARAPL1. Up-regulated 15 genes: PARP1, BNIP3, P4HB, ATIC, IKBKE, ITGB4, VMP1, PTK6, EIF4EBP1, GAPDH, ATG9B, ERO1A, TMEM74, CDKN2A, BIRC5. GO and KEGG analysis showed that these genes were significantly associated with autophagy and mitochondria (animals). Multi-factor COX analysis of autophagy-related genes showed that ITGA6, ERO1A, FKBP1A, BAK1, CCR2, FADD, EDEM1, ATG10, ATG4A, DLC1, VAMP7, ST13 were identified as independent prognostic indicators. According to the multivariate COX proportional hazard regression model, there was a significant difference in the survival rate observed between the high-risk group (n=124) and the low-risk group (n=126) during the 10-year follow-up (p<0.05). Univariate COX analysis showed that tumor stage, T, M and N stages, and risk score were all related to the survival rate of female lung adenocarcinoma patients. Multivariate COX analysis found that autophagy-related risk scores were independent predictors, with an AUC value of 0.842. At last, there are autophagy genes differentially expressed among various clinicopathological parameters: ATG4A, BAK1, CCR2, DLC1, ERO1A, FKBP1A, ITGA6.Conclusion: The risk score can be used as an independent prognostic indicator for female patients with lung adenocarcinoma. The autophagy genes ITGA6, ERO1A, FKBP1A, BAK1, CCR2, FADD, EDEM1, ATG10, ATG4A, DLC1, VAMP7, ST13 were identified as prognostic genes in female lung adenocarcinoma, which may be the targets of treatment in the future.

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