Marker For Adenocarcinoma Research Articles

DNA Methylation of HOXA11 Gene as Prognostic Molecular Marker in Human Gastric Adenocarcinoma.

Hypermethylation of tumor suppressor genes and hypomethylation of oncogenes might be identified as possible biomarkers in gastric cancer (GC). We aimed to assess the DNA methylation status of selected genes in GC tissue samples and evaluate these genes’ prognostic importance on patient survival. Patients (99) diagnosed with GC and who underwent gastrectomy were included. We selected a group of genes (RAD51B, GFRA3, AKR7A3, HOXA11, TUSC3, FLI1, SEZ6L, GLDC, NDRG) which may be considered as potential tumor suppressor genes and oncogenes. Methylation of the HOXA11 gene promoter was significantly more frequent in GC tumor tissue (p = 0.006) than in healthy gastric mucosa. The probability of surviving longer (71.2 months (95% CI 57–85.3) vs. 44.3 months (95% CI 34.8–53.9)) was observed with unmethylated HOXA11 promoter in cancer tissues. Survival in patients with a methylation of HOXA11 promoter either in healthy gastric mucosa or gastric cancer tissue was twice as high as in patients with a methylation of HOXA11 promoter in both healthy gastric mucosa and cancer tissue (61.2 months (95% CI 50.9–71.4) vs. 28.5 months (95% CI 20.8–36.2)). Multivariate Cox analysis revealed the HOXA11 methylation as significantly associated with patients’ survival (HR = 2.4, 95% CI 1.19–4.86). Our results suggest that the HOXA11 gene might be a potential prognostic molecular marker in patients with gastric adenocarcinoma.

Messenger RNA of FCGR3A and FCGR3B Genes as Monitoring Markers of Clear Cell Renal Adenocarcinoma (a Pilot Study).

We used 125 tumor samples from patients with a histologically confirmed diagnosis of renal cancer T1-4N0-1M0-1. A method described by Chomczynski and Sacchi was used to isolate nucleic acids. The mRNA levels were determined using a reverse transcription polymerase chain reaction and calculated according to ΔΔCt formula, taking into account the reaction efficiency. mRNA of the FCGR3A gene was detected in all tumor tissue samples under study; in contrast, mRNA of the FCGR3B gene was found only in 92.0% (115/125) of cases. In tumors classified as pT1, the mRNA content of the FCGR3A gene was significantly lower than that in tumor samples of pT3 size. There was the significant increase in the mRNA content of both genes with an increase in tumor grade, as well as in the cases with distant metastases. The presence of a tumor thrombus in the inferior vena cava system was accompanied by a significant increase in the mRNA content of the FCGR3A gene. In tumor tissue samples from patients with clear cell renal cancer, the predominant production of the FCGR3A mRNA was observed in comparison with the FCGR3B mRNA. The revealed relationship of an increased amount of the FCGR3A mRNA and, in some cases, the FCGR3B mRNA with a number of clinical and morphological factors enables to consider the mRNA level of the genes as new monitoring biomarkers.

Temporality of body mass index, blood tests, comorbidities and medication use as early markers for pancreatic ductal adenocarcinoma (PDAC): a nested case–control study

ObjectivePrior studies identified clinical factors associated with increased risk of pancreatic ductal adenocarcinoma (PDAC). However, little is known regarding their time-varying nature, which could inform earlier diagnosis. This study assessed...

Integrated Bioinformatics Analysis for Identifying the Significant Genes as Poor Prognostic Markers in Gastric Adenocarcinoma.

Gastric adenocarcinoma (GAC) is the most common histological type of gastric cancer and imposes a considerable health burden globally. The purpose of this study was to identify significant genes and key pathways participated in the initiation and progression of GAC. Four datasets (GSE13911, GSE19826, GSE54129, and GSE79973) including 171 GAC and 77 normal tissues from Gene Expression Omnibus (GEO) database were collected and analyzed. Through integrated bioinformatics analysis, we obtained 69 commonly differentially expressed genes (DEGs) among the four datasets, including 20 upregulated and 49 downregulated genes. The prime module in protein-protein interaction network of DEGs, including ADAMTS2, COL10A1, COL1A1, COL1A2, COL8A1, BGN, and SPP1, was enriched in protein digestion and absorption, ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and amoebiasis. Furthermore, expression and survival analysis found that all seven hub genes were highly expressed in GAC tissues and 6 of them (except for SPP1) were able to predict poor prognosis of GAC. Finally, we verified the 6 high-expressed hub genes in GAC tissues via immunohistochemistry, Western blot, and RNA quantification analysis. Altogether, we identified six significantly upregulated DEGs as poor prognostic markers in GAC based on integrated bioinformatical methods, which could be potential molecular markers and therapeutic targets for GAC patients.

A Comprehensive Analysis of HAVCR1 as a Prognostic and Diagnostic Marker for Pan-Cancer.

Hepatitis A virus cellular receptor (HAVCR1) is a type-1 integral membrane glycoprotein that plays a key role in immunity and renal regeneration and is abnormally expressed in various tumor types. Nonetheless, the function of HAVCR1 in pan-cancer remains unknown. In this study, we comprehensively analyzed the expression and promoter methylation level of HAVCR1 and assessed the immune cell infiltration, correlation between stromal and immune cell admixture, CD (Cluster of Differentiation) and HAVCR1 expression and prognostic value of HAVCR1 mRNA expression in Liver hepatocellular carcinoma (LIHC) and Pancreatic adenocarcinoma (PAAD). Our results showed that HAVCR1 was overexpressed while the promoter methylation of HAVCR1 was decreased in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. HAVCR1 was associated with increased infiltration of B cells, CD8 cells, macrophages, neutrophils and Dendritic cells in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. HAVCR1 expression was positively correlated with the immune, stromal and estimate scores of Pancreatic adenocarcinoma and the stromal and estimate scores of Liver hepatocellular carcinoma. Furthermore, HAVCR1 expression was correlated with other immune molecules such as HHLA2 (Human endogenous retrovirus-H long terminal repeat-associating protein 2), CD44 and TNFRSF4 (TNF Receptor Superfamily Member 4) in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma. During Kaplan-Meier analysis, high HAVCR1 expression in Liver hepatocellular carcinoma and Pancreatic adenocarcinoma correlated with poor survival. A marginally significant p-value (p = 0.051) was obtained when the relationship between HAVCR1 expression in Liver hepatocellular carcinoma and prognosis was analyzed, attributed to the small sample size. Overall, we provided compelling evidence that HAVCR1 could be a prognostic and diagnostic marker for Liver hepatocellular carcinoma and Pancreatic adenocarcinoma.

Identification of significant prognostic risk markers for pancreatic ductal adenocarcinoma: a bioinformatic analysis.

This study aimed to identify novel prognostic biomarkers of pancreatic ductal adenocarcinoma (PDAC) using bioinformatics analyzes. Clinical information, microRNAs (miRNAs), and genes expression profile data from PDAC cases were downloaded from the Cancer Genome Atlas (TCGA) database. The potential prognostic risk miRNAs and genes were screened using the Elastic Net Cox proportional risk regression hazards (EN-COX) model. The receiver operating characteristic (ROC) curve and the Kaplan-Meier (KM) curve were used to identify miRNAs and genes of significant prognostic risk. Furthermore, significant prognostic risk miRNAs were functional enrichment analyses based on their target genes. Furthermore, the survival analyzes of the hub genes were validated through OncoLnc. Complete clinical records and expression data of 797 miRNAs and 19969 genes from 137 PDAC cases were obtained, of which 59 potential prognostic risk factors, including 54 genes and 5 miRNAs, were selected by EN-COX analyzes. A total of 17 significant prognostic risk markers were identified (all P<0.05), including 16 genes and 1 miRNA (miRNA-125a). The miRNA-125a target genes were found in the MiRWalk database and the function enrichment analyzes were performed in the the DAVID website. Furthermore, according to data from the Oncomine and Human Protein Atlas (HPA) databases, the mRNA and protein level of frizzled class receptor 8 (FZD8) were overexpressed in pancreatic cancer tissues compared to the corresponding noncancer normal tissues (P<0.001). However, both glutathione S-transferase mu 4 (GSTM4) and inducible T cell costimulator ligand (ICOSLG) were negatively regulated in tissues of pancreatic cancer tissues (P<0.001). Finally, survival analysis was used to validate these factors by the OncoLnc database, and the results revealed that overexpression of ICOSLG was associated with a better prognosis (P=0.025). This study showed that the expression levels of FZD8, GSTM4 and ICOSLG were significantly different between PDAC and non-tumor tissues, especially ICOSLG, which could be a prognostic indicator and therapeutic target for PDAC.

Long Noncoding RNA SNHG7 Is a Diagnostic and Prognostic Marker for Colon Adenocarcinoma.

Numerous studies have shown that long noncoding RNAs (lncRNAs) play a critical role in the malignant progression of cancer. However, the potential involvement of lncRNAs in colon adenocarcinoma (COAD) remains unexplored. In this study, the expression of lncRNA SNHG7 in colon cancer tissues and its correlation with clinical characteristics were analyzed based on data from The Cancer Genome Atlas (TCGA) database. SNHG7 was found to be highly expressed in 17 types of cancer, including COAD. Next, TCGA data were further investigated to identify differentially expressed genes, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. In addition, the relationship between SNHG7 expression and clinical features were analyzed. SNHG7 expression was found to be a potentially valuable indicator for COAD diagnosis and prognosis. Finally, gene set enrichment analysis showed that SNHG7 may affect lupus erythematosus and reactome cellular senescence, possibly influencing the prognosis of patients with COAD. Altogether, these results suggest that SNHG7 may be associated with the occurrence and development of COAD, having potential diagnostic and prognostic value.

Comprehensive characterization and functional implications of mesenchymal stem cell-related genes in pancancer: A new horizon for immunotherapy.

e14577 Background: Accumulated evidence demonstrates that mesenchymal stem cells (MSCs) contribute to tissue regeneration, tumor progression, chemotherapy resistance, and mediate tumor immune escape by modulating the stroma and immunity of the tumor microenvironment. However, little is known about the role of MSCs in cancer patients receiving immunotherapy. Therefore, we investigated the comprehensive characterization of MSC-related genes and their functional implications in pan-cancer immunotherapy. Methods: We performed a pan-cancer analysis of 59 MSC-related genes, which was used to calculate an MSC score with single sample gene set enrichment analysis. Multivariate Cox regression analysis was performed to identify a potential independent prognostic marker for cancer. TIDE algorithm and neural network were utilized to assess the predictive accuracy of MSC-related genes for immunotherapy. Results: MSC-related gene expression showed significant differences inconsistently between normal and tumor samples across the 33 cancer types (p &lt; 0.05). Cox regression analysis suggested that the MSC score is an independent prognostic marker for papillary renal cell carcinoma (TCGA; OS, RFS and DSS, all p &lt; 0.05), mesothelioma (TCGA and GSE29354, OS, all p &lt; 0.05), glioma (TCGA and GSE107850, OS, all p &lt; 0.05), and stomach adenocarcinoma (TCGA, GSE84437, GSE15459, GSE13861 and GSE62254, OS; GSE13861 and GSE62254, RFS; all p &lt; 0.05). The abundance of fibroblasts was also more representative of the MSC score compared to the stromal score. Samples with a high MSC score were predicted to have low responsiveness to immunotherapy, which was validated across seven immune checkpoint therapy datasets (IMvigor210, 27.52% (low) vs 18.12% (high); GSE78220, 64.28% (low) vs 42.86% (high); GSE135222, 30.77% (low) vs 28.57% (high); GSE165252, 36.11% (low) vs 28.57% (high); GSE79671; 38.89% (low) vs 33.33% (high); PRJEB25780, 45.45% (low) vs 8.70% (high); GSE176307, 22.22% (low) vs 13.64% (high)). TIDE algorithm and Neural network demonstrated a good predictive accuracy of MSC-related genes for immunotherapy (CESC, COAD, DLBC, GBM, KIRC, LAML, LIHC, LUAD, LUSC, MESO, OV, PCPG, PRAD, SARC, SKCM, THCA, UCEC, and UCS; all ROC ≥0.9). Conclusions: We characterized the MSC-related genes across multiple cancer types and highlighted their potential as a predictive biomarker for immunotherapy response and prognosis. A prospective clinical trial is warranted to confirm these findings.

EVALUATION OF NAPSIN A EXPRESSION IN LUNG CANCERS AND ITS COMPARISON WITH THYROID TRANSCRIPTION FACTOR 1

Introduction: Lung cancer is the leading cause of cancer mortality in the world. With the development of new, successful treatments for adenocarcinoma, it is essential to subtype Non- Small Cell Lung Carcinoma whenever possible. Thyroid Transcription Factor-1 is a promising marker for lung adenocarcinoma but its sensitivity and specificity is limited. Napsin A is a new marker that may be useful as a part of immunohistochemistry panel to classify poorly differentiated lung carcinoma on small biopsies. Aim: To study the expression of Napsin A in lung cancer and to compare it with TTF-1 that has already recognized as a useful marker for lung adenocarcinoma. Methodology: This is a retrospective study. By analyzing the histopathology records during the period of 2015 - 2017, histopathological slides of biopsy proven 50 malignant lung cases were collected. Napsin A expression was tested and compared with TTF1. Results: Adenocarcinoma is the commonest type. Most common age group is 51-60 years with male female ratio is 2.7:1. Smokers have increased risk for malignancy. Napsin A and TTF1 showed similar sensitivity and the specificity of Napsin A was higher than TTF1 to lung adenocarcinoma. Napsin A showed higher sensitivity than TTF1 to exclude lung small cell carcinoma. Conclusion: Napsin A is almost limited to adenocarcinoma, whereas TTF-1 is not so specific. Although TTF-1 is expressed in majority of adenocarcinomas, its expression is also noted in most of the small-cell lung carcinomas. Hence Napsin A can be used as an exclusionary marker for small cell carcinoma. Key words: Lung cancer, Napsin A, Small biopsy, Thyroid transcription factor 1.

Neoadjuvant chemotherapy endows CD9 with prognostic value that differs between tumor and stromal areas in patients with pancreatic cancer

BackgroundThe selective pressure imposed by chemotherapy creates a barrier to tumor eradication and an opportunity for metastasis and recurrence. As a newly discovered stemness marker of pancreatic ductal adenocarcinoma (PDAC), the impact of CD9 on tumor progression and patient's prognosis remain controversial.MethodsA total of 179 and 211 PDAC patients who underwent surgical resection with or without neoadjuvant chemotherapy, respectively, were recruited for immunohistochemical analyses of CD9 expression in both tumor and stromal areas prior to statistical analyses to determine the prognostic impact and predictive accuracy of CD9.ResultsThe relationship between CD9 and prognostic indicators was not significant in the non‐neoadjuvant group. Nevertheless, CD9 expression in both tumor (T‐CD9) and stromal areas (S‐CD9) was significantly correlated with the clinicopathological features in the neoadjuvant group. High levels of T‐CD9 were significantly associated with worse OS (p = 0.005) and RFS (p = 0.007), while positive S‐CD9 showed the opposite results (OS: p = 0.024; RFS: p = 0.008). Cox regression analyses identified CD9 in both areas as an independent prognostic factor. The T&S‐CD9 risk‐level system was used to stratify patients with different survival levels. The combination of T&S‐CD9 risk level and TNM stage were accurate predictors of OS (C‐index: 0.676; AIC: 512.51) and RFS (C‐index: 0.680; AIC: 519.53). The calibration curve of the nomogram composed of the combined parameters showed excellent predictive consistency for 1‐year RFS. These results were verified using a validation cohort.ConclusionNeoadjuvant chemotherapy endows CD9 with a significant prognostic value that differs between tumor and stromal areas in patients with pancreatic cancer.

Multi-Phase, Contrast-Enhanced Computed Tomography-Based Radiomic Prognostic Marker of Non-Metastatic Pancreatic Ductal Adenocarcinoma.

Simple SummaryPatients with PDA lesions with high attenuation values had longer OS in the RPC and BRPC/LAPC groups and were more likely to undergo a surgical resection after neoadjuvant chemotherapy. These results indicate that intra-tumoral contrast enhancement on CT is an independent prognostic factor in patients with non-metastatic PDA.Background/Aim: This study investigated the predictive ability of intra-tumor enhancement on computed tomography (CT) for the outcomes of patients with pancreatic ductal adenocarcinoma (PDA). Methods: Multi-phase, contrast-enhanced CT (including unenhanced, pancreatic parenchymal phase (PPP) and portal venous phase (PVP)) images of patients diagnosed with non-metastatic PDA were analyzed to investigate prognostic factors. Results: Two hundred ninety-eight patients with PDA (159 with resectable pancreatic cancer (RPC) and 139 with borderline resectable pancreatic cancer (BRPC)/locally advanced pancreatic cancer (LAPC)) were included. The attenuation values of PDA during the PPP (94.5 vs. 60.7 HU; p <0.001) and PVP (101.5 vs. 75.5 HU; p <0.001) were higher in patients with RPC than in those with BRPC/LAPC. Well-enhanced PDA during the PPP was associated with longer overall survival in the RPC group (27.9 vs. 15.4 months; p <0.001) and the BRPC/LAPC group (22.7 vs. 13.6 months; p = 0.024). Patients with BRPC/LAPC who underwent neoadjuvant treatment and had well-enhanced PDA during the PPP were more likely to undergo resection. Although tumor size was also an independent prognostic factor, it was not correlated with intra-tumoral enhancement during the PPP. Conclusions: Intra-tumoral contrast enhancement on CT is an independent prognostic factor in patients with non-metastatic PDA.

Candidate diagnostic and prognostic markers for pancreatitis and pancreatic ductal adenocarcinoma

Diagnostic markers are desperately needed for early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity of PDA marker expression was analyzed by interrogating quantitative dot plots of single cell (sc) RNAseq for 3021 candidate genes in tumor samples from a mouse model for PDA (KIC) at early and late stages of PDA progression compared to normal pancreas. Protein markers were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines. Additional candidate genes were identified from signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes. Developmental progression of cancer was revealed in seven classes of PDA markers expressed in cancer cells and stroma. The earliest diagnostic markers (47 genes) were specifically expressed in epithelial cancer cells in early, but not late, PDA tumors. Other markers were first elevated in epithelial cancer cells of late stage tumors (288 genes), or in both epithelial and mesenchymal cells (740 genes), or only in mesenchymal cells (216 genes). Stromal markers were differentially expressed in early‐ and/or late‐PDA neoplasia (594 genes). Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and acinar‐specific homozygous deletion of differentiation transcription factors (dTFs), were screened for early expression of all PDA markers identified in KIC neoplasia. Select diagnostic markers were validated by immunohistochemistry in mouse and human samples of normal pancreas, early‑ and late‐stage PDA. Prognostic markers from TCGA were identified that showed differential and cell type‐specific expression in PDA. Here we present diagnostic and prognostic markers for disease progression from pancreatitis to late‐stage PDA.

YTHDF2 is a novel diagnostic marker of endometrial adenocarcinoma and endometrial atypical hyperplasia/ intraepithelial neoplasia

Numerous studies show that some biomarkers are aberrantly expressed in endometrial endometrioid adenocarcinoma (EMAC) and endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN) compared to endometrial benign lesions. Because of low sensitivity and/or specificity, the utility of these markers to distinguish EMAC and EAH/EIN from benign endometrial lesions is limited. YTH domain family 2 (YTHDF2) is a functional N6-methyladenosine (m6A)-specific reader protein that mainly regulates mRNA stability. Aberrant YTHDF2 expression has been reported in many cancers and plays important functions in tumorigenesis and cancer progression. However, its expression in endometrial benign and malignant lesions has not been investigated. We evaluated YTHDF2 mRNA and protein expression in EMAC and normal endometrium using the UALCAN database and validated the bioinformatic results in EMAC cells using qRT-PCR, Western blot, and immunohistochemical (IHC) staining. We found that YTHDF2 was weakly expressed in normal endometrium, benign endometrial lesions, endometrial hyperplasia without atypia, and adenomyosis. In contrast, YTHDF2 was upregulated in EAH/EIN and EMAC. These results indicate that YTHDF2 immunostaining may be a useful tool to distinguish EAH/EIN from EHWA. Finally, YTHDF2 expression can accurately assess the depth of myometrial invasion (DMI) in EMAC when EMAC coexists with adenomyosis.

Prognostic impact of tumor-infiltrating lymphocytes and neutrophils in resected non-small cell lung carcinoma

The prognostic impact of tumor-infiltrating lymphocytes (TILs) has been determined in non-small cell lung carcinoma; however, there is no standardized method for counting TILs. In this report, we applied the method proposed by the International Immuno-Oncology Biomarkers Working Group for the assessment of TILs to count the number of tumor-infiltrating neutrophils (TINs). We then analyzed the association between TIL counts, TIN counts, and clinicopathological factors in lung cancer. We retrospectively analyzed a series of 1191 Japanese patients with resected lung adenocarcinoma and squamous cell carcinoma, which were restaged according to the eighth edition of the TNM staging system. Tumors were classified according to the 2015 WHO classification of lung carcinoma. Recurrence-free probability (RFP) and overall survival (OS) were analyzed using the log-rank test and Cox proportional hazard model. Using multivariate analysis for patient outcome in patients with adenocarcinoma, high TIN counts were an independent prognostic factor for worse RFP (hazard ratio [HR]: 1.94, p<0.001) and worse OS (hazard ratio [HR]: 1.75, p=0.006). On the other hand, TIL counts were not related to patient outcome. We have demonstrated that high TINs are unfavorable prognostic markers for resected lung adenocarcinoma. In resected lung squamous cell carcinoma, TIL and TIN counts were not related to patient prognosis. It has been suggested that the immune response to cancer cells may differ depending on the histological type. An understanding of how neutrophils are programmed to perform protumor activities is necessary for the future design of targeted immunotherapies.

Ferroptosis-Related Long Noncoding RNAs as Prognostic Marker for Colon Adenocarcinoma.

Background The incidence of colon adenocarcinoma (COAD) has been increasing over time. Although ferroptosis and long noncoding RNAs (lncRNAs) have been extensively reported to participate in the tumorigenesis and development of COAD, few studies have investigated the role of ferroptosis-related lncRNAs in the prognosis of COAD. Methods Gene-sequencing and clinical data for COAD were obtained from The Cancer Genome Atlas database. The coexpression network was constructed using known ferroptosis-related genes. Cox and least absolute shrinkage and selection operator regression were used to screen ferroptosis-related lncRNAs with prognostic value and to identify a predictive model of COAD. Patients with COAD were divided into low- and high-risk groups according to their risk score. Cases of COAD in the International Cancer Genome Consortium database were included as the testing cohort. Results In total, nine lncRNAs (LINC02381, AC105219.1, AC009283.1, LINC01011, ELFN1-AS1, EIF3J-DT, NKILA, LINC01063, and SNHG16) were considered prognostic factors for COAD. Then, a risk score model was established. The overall survival rate of COAD patients was negatively associated with the risk score. Kaplan–Meier analyses in the original and testing cohorts showed similar results. The expression of the lncRNAs in tissue was consistent with the risk score, and the relationship with tumor mutation burden, immunity, and drug sensitivity presented a marked link between the signature and COAD. A nomogram was established for clinical applications. Conclusions Nine ferroptosis-related lncRNAs and the established signature have a certain predictive value for prognosis of COAD patients and can be used as potential research targets for exploring treatment of COAD.

Primary malignant peritoneal mesothelioma mimicking tuberculous peritonitis: A case report

BACKGROUNDMalignant peritoneal mesothelioma (MPM) is a rare malignancy arising in mesothelial cells in the peritoneum. It can be mistaken for many other diseases, such as peritoneal carcinomatosis and tuberculous peritonitis (TBP), because its clinical manifestations are often nonspecific. Therefore, the diagnosis of MPM is often challenging and delayed.CASE SUMMARYA 42-year-old man was referred to our hospital with lower abdominal pain for 1 wk and ascites observed under abdominal sonography. His laboratory findings revealed an isolated elevated tumor marker of carcinoma antigen 125 (167.4 U/mL; normal, < 35 U/mL), and contrast enhanced computed tomography showed peritoneal thickening. Thus, differential diagnoses of TBP, carcinomatosis of an unknown nature, and primary peritoneal malignancy were considered. After both esophagogastroduodenoscopy and colonoscopy produced negative findings, laparoscopic intervention was performed. The histopathological results revealed mesothelioma invasion into soft tissue composed of a papillary, tubular, single-cell arrangement of epithelioid cells. In addition, immunohistochemical staining was positive for mesothelioma markers and negative for adenocarcinoma markers. Based on the above findings, TBP was excluded, and the patient was diagnosed with MPM.CONCLUSIONIt is important to distinguish MPM from TBP because they have similar symptoms and blood test findings.

MUC6 expression is a preferable prognostic marker for invasive mucinous adenocarcinoma of the lung.

Gastric gland mucin consists of core protein MUC6 with residues heavily glycosylated by unique O-glycans carrying α1,4-linked N-acetylglucosamine (αGlcNAc). αGlcNAc-glycosylated MUC6 protein is seen in normal gastric and duodenal glands. Decreased αGlcNAc glycosylation on MUC6-positive tumor cells is often observed in premalignant lesions of the stomach, pancreas, and bile duct, and decreased MUC6 expression is seen in invasive cancer of these organs. Lung cancer (LC) is the most common cause of cancer death worldwide. Recently, the adenocarcinoma subtype has become the most common histological subtype of LC, and one of its invasive forms is invasive mucinous adenocarcinoma (IMA). Currently, prognostic markers of LC IMA are unknown. Here, we analyzed MUC5AC, MUC6, and αGlcNAc expression in 54 IMA LC cases. MUC5AC was positively expressed in 50 (93%), MUC6 in 38 (70%), and αGlcNAc in 19 (35%). Each expression level was scored from 0 to 3. The αGlcNAc expression score was significantly decreased relative to MUC6 (P < 0.001). Interestingly, disease-free survival was significantly higher in MUC6-positive than MUC6-negative cases based on the log-rank test (P = 0.021). For in vitro analysis, we ectopically expressed MUC6 in A549 cells, derived from LC and harboring a KRAS mutation. MUC6-expressing A549 cells showed significantly lower proliferation, motility, and invasiveness than control cells. Finally, F-actin staining in MUC6-expressing cells revealed a decrease or loss of filopodia associated with decreased levels of FSCN transcripts, which encodes an actin-bundling protein fascin1 necessary for cell migration. We conclude that MUC6 expression is a preferable prognostic biomarker in IMA LC.

S100A4 Is a Strong Negative Prognostic Marker and Potential Therapeutic Target in Adenocarcinoma of the Stomach and Esophagus.

Deregulated Wnt-signaling is a key mechanism driving metastasis in adenocarcinoma of the gastroesophageal junction and stomach (AGE/S). The oncogene S100A4 was identified as a Wnt-signaling target gene and is known to promote metastasis. In this project, we illuminate the role of S100A4 for metastases development and disease prognosis of AGE/S. Five gastric cancer cell lines were assessed for S100A4 expression. Two cell lines with endogenous high S100A4 expression were used for functional phenotyping including analysis of proliferation and migration after stable S100A4 knock-down. The prognostic value of S100A4 was evaluated by analyzing the S100A4 expression of tissue microarrays with samples of 277 patients with AGE/S. S100A4 knock-down induced lower migration in FLO1 and NCI-N87 cells. Treatment with niclosamide in these cells led to partial inhibition of S100A4 and to reduced migration. Patients with high S100A4 expression showed lower 5-year overall and disease-specific survival. In addition, a larger share of patients in the S100A4 high expressing group suffered from metachronous metastasis. This study identifies S100A4 as a negative prognostic marker for patients with AGE/S. The strong correlation between S100A4 expression, metastases development and patient survival might open opportunities to use S100A4 to improve the prognosis of these patients and as a therapeutic target for intervention in this tumor entity.

Serum exosomal proteomics analysis of lung adenocarcinoma to discover new tumor markers

BackgroundAmong the most aggressive and rapidly lethal types of lung cancer, lung adenocarcinoma is the most common type. Exosomes, as a hot area, play an influential role in cancer. By using proteomics analysis, we aimed to identify potential markers of lung adenocarcinoma in serum.MethodsIn our study, we used the ultracentrifugation method to isolate serum exosomes. The Liquid chromatography-mass spectrometry (LC–MS) and bioinformatics analysis were used to identify potential serum exosomal proteins with altered expression among patients with advanced lung adenocarcinoma, early lung adenocarcinoma, and healthy controls. A western blot (WB) was performed to confirm the above differential expression levels in a separate serum sample-isolated exosome, and immunohistochemistry (IHC) staining was conducted to detect expression levels of the above differential proteins of serum exosomes in lung adenocarcinoma tissues and adjacent tissues. Furthermore, we compared different expression models of the above differential proteins in serum and exosomes.ResultAccording to the ITGAM (Integrin alpha M chain) and CLU (Clusterin) were differentially expressed in serum exosomes among different groups as well as tumor tissues and adjacent tissues. ITGAM was significantly and specifically enriched in exosomes. As compared to serum, CLU did not appear to be significantly enriched in exosomes. ITGAM and CLU were identified as serum exosomal protein markers of lung adenocarcinoma.ConclusionsThis study can provide novel ideas and a research basis for targeting lung adenocarcinoma treatment as a preliminary study.

High Expression of NT5DC2 Is a Negative Prognostic Marker in Pulmonary Adenocarcinoma.

Simple SummaryLung cancer is the leading cause of cancer related deaths and non-small cell lung cancer (NSCLC) is its most relevant subtype. Here, we present data on p53 co-playing 5′-Nucleotidase Domain-Containing Protein 2 (NT5DC2) protein- and gene-expression and its clinical implication and prognostic value. NT5DC2 overexpression was associated with advanced lymphonodal spread and reduced survival in patients with adenocarcinoma of the lung. Moreover, dysregulated p53 in combination with overexpressed NT5DC2 might promote malignancy by interaction with cancer associated fibroblasts.Via immunohistochemistry (IHC) on tissue micro arrays (TMA) clinical and prognostic impact of p53 co-playing 5′-Nucleotidase Domain-Containing Protein 2 (NT5DC2) protein expression was evaluated in 252 NSCLC patients. Confirmatory, gene expression database. mRNA levels of NT5DC2 were studied in 1925 NSCLC patients. High protein expression of NT5DC2 resulted in reduced median overall survival (OS) of patients with stage I-III adenocarcinoma (ADC) (Log Rank p = 0.026, HR 2.04 (1.08–3.87)), but not in squamous cell carcinoma (SCC) (p = 0.514, HR 0.87 (0.57–1.33)). Findings on OS were reproduced via gene expression analysis in ADC (p < 0.001, HR 1.64 (1.30–2.08)) and SCC (p = 0.217, HR 0.86 (0.68–1.09)). Yet, NT5DC2 mRNA levels were higher in SCC compared to ADC (p < 0.001) and in pN2 tumors compared to pN0/1 tumors (p = 0.001). Likewise, NT5DC2 protein expression associated with high-grade SCC. Moreover, NT5DC2 expression was positively correlated with p53 protein (p = 0.018) and TP53 gene expression (p < 0.001) and its survival effect was p53 dependent. While p53 expression was negatively associated with the presence of CD34+ cancer associated fibroblasts (CAFs), NT5DC2 expression insignificantly tended to higher levels of SMA+ CAFs (p = 0.065).