Potential Marker For Poor Prognosis Research Articles

Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals immune suppression subtypes and establishes a novel signature for determining the prognosis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer with lower survival rates. Recent advancements in targeted therapies and immunotherapies targeting immune checkpoints have achieved remarkable success, there is still a large percentage of LUAD that lacks available therapeutic options. Due to tumor heterogeneity, the diagnosis and treatment of LUAD are challenging. Exploring the biology of LUAD and identifying new biomarker and therapeutic targets options are essential. We performed single-cell RNA sequencing (scRNA-seq) of 6 paired primary and adjacent LUAD tissues, and integrative omics analysis of the scRNA-seq, bulk RNA-seq and whole-exome sequencing data revealed molecular subtype characteristics. Our experimental results confirm that CDC25C gene can serve as a potential marker for poor prognosis in LUAD. We investigated aberrant gene expression in diverse cell types in LUAD via the scRNA-seq data. Moreover, multi-omics clustering revealed four subgroups defined by transcriptional profile and molecular subtype 4 (MS4) with poor survival probability, and immune cell infiltration signatures revealed that MS4 tended to be the immunosuppressive subtype. Our study revealed that the CDC25C gene can be a distinct prognostic biomarker that indicates immune infiltration levels and response to immunotherapy in LUAD patients. Our experimental results concluded that CDC25C expression affects lung cancer cell invasion and migration, might play a key role in regulating Epithelial-Mesenchymal Transition (EMT) pathways. Our multi-omics result revealed a comprehensive set of molecular attributes associated with prognosis-related genes in LUAD at the cellular and tissue level. Identification of a subtype of immunosuppressive TME and prognostic signature for LUAD. We identified the cell cycle regulation gene CDC25C affects lung cancer cell invasion and migration, which can be used as a potential biomarker for LUAD.

Free triiodothyronine to free thyroxine ratio as a marker of poor prognosis in euthyroid patients with acute coronary syndrome and diabetes after percutaneous coronary intervention.

In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI.

Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion

Bromodomain-containing protein 4 (BRD4), the major component of bromodomain and extra-terminal domain (BET) protein family, has important functions in early embryonic development and cancer development. However, the posttranslational modification of BRD4 is not well understood. Multiple approaches were used to explore the mechanism of PRMT1-mediated BRD4 methylation and to determine the biological functions of BRD4 and PRMT1 in ovarian cancer. Here we report that BRD4 is asymmetrically methylated at R179/181/183 by PRMT1, which is antagonized by the Jumonji-family demethylase, JMJD6. PRMT1 is overexpressed in ovarian cancer tissue and is a potential marker for poor prognosis in ovarian cancer patients. Silencing of PRMT1 inhibited ovarian cancer proliferation, migration, and invasion in vivo and in vitro. PRMT1-mediated BRD4 methylation was found to promote BRD4 phosphorylation. Compared to BRD4 wild-type (WT) cells, BRD4 R179/181/183K mutant-expressing cells showed reduced ovarian cancer metastasis. BRD4 arginine methylation is also associated with TGF-β signaling. Our results indicate that arginine methylation of BRD4 by PRMT1 is involved in ovarian cancer tumorigenesis. Targeting PRMT1-mediated arginine methylation may provide a novel diagnostic target and an effective therapeutic strategy for ovarian cancer treatment.

Pretreatment endocrine symptoms and recurrence-free survival among young premenopausal patients with breast cancer: a prospective cohort study.

Pretreatment endocrine symptoms in premenopausal patients might be considered as a potential marker of poor prognosis. We conducted a cohort study to evaluate the association between endocrine symptoms prior to treatment and recurrence-free survival (RFS) among premenopausal patients with breast cancer aged ⩽40 years. Data were obtained from a prospective cohort study (NCT03131089) conducted at the Samsung Medical Center from 2013 to 2021. We included patients aged ⩽40 years who had been diagnosed with breast cancer. The primary outcome measure was RFS. Endocrine symptoms were measured using the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES). We also calculated the hazard ratio (HR) for recurrence or all-cause mortality by comparing the tertiles of the FACT-ES score at diagnosis. Among the 977 participants, the mean (standard deviation) age was 35.3 (3.9) years. At diagnosis, 17.2% of the patients had at least one severe endocrine symptom. During 3512 person-years of follow-up, the high symptom group had a worse RFS than the low-symptom group [HR = 2.05; 95% confidence interval (CI) = 1.19-3.54]. In particular, hot flashes (HR = 5.59; 95% CI = 1.96-15.93) and breast sensitivity (HR = 1.82; 95% CI = 1.00-3.32) were associated with reduced RFS. Close monitoring of pretreatment endocrine symptoms may be important in patients diagnosed with breast cancer at a young age.

Identification and characterization of sex-dependent gene expression profile in glioblastoma.

Glioblastoma (GBM) is the most lethal primary tumor in the human brain and lacks favorable treatment options. Sex differences in the outcome of GBM are broadly acknowledged, but the underlying molecular mechanisms remain largely unknown. To identify the sex-dependent critical genes in the progression of GBM, raw data from several microarray datasets with the same array platform were downloaded from the Gene Expression Omnibus (GEO) database. These datasets included tumorous and normal tissue from patients with GBM and crucial sex features. Then, the differentially expressed genes (DEGs) in female and male tumors were identified via bioinformatics analysis, respectively. Functional signatures of the identified DEGs were further annotated by Gene Ontology (GO) and pathway enrichment analyses. Venn diagram and functional protein-protein interaction (PPI) network analyses were performed to screen out the sex-specific DEGs. Survival analysis of patients with differences in the expression level of selected genes was then carried out using the data from The Cancer Genome Atlas (TCGA). Here, we showed that ECT2, AURKA, TYMS, CDK1, NCAPH, CENPU, OIP5, KIF14, ASPM, FBXO5, SGOL2, CASC5, SHCBP1, FN1, LOX, IGFBP3, CSPG4, and CD44 were enriched in female tumor samples, whereas TNFSF13B, CXCL10, CXCL8, CXCR4, TLR2, CCL2, and FCGR2A were enriched in male tumor samples. Among these key genes, interestingly, ECT2 was associated with increased an survival rate for female patients, whileTNFSF13B could be regarded as a potential marker of poor prognosis in male patients. These results suggested that sex differences in patients may be attributed to the heterogeneous gene activity, which might influence the oncogenesis and the outcomes of GBM.

Fanconi Anemia Complementation Group E, a DNA Repair-Related Gene, Is a Potential Marker of Poor Prognosis in Hepatocellular Carcinoma

Introduction: Fanconi anemia complementation group E (FANCE) is a Fanconi anemia (FA) pathway gene that regulates DNA repair. We evaluated the clinical relevance of FANCE expression in hepatocellular carcinoma (HCC). Methods: First, the associations between the expression of FA pathway genes including FANCE and clinical outcomes in HCC patients were analyzed in 2 independent cohorts: The Cancer Genome Atlas (TCGA, n = 373) and our patient cohort (n = 53). Localization of FANCE expression in HCC tissues was observed by immunohistochemical staining. Gene set enrichment analysis (GSEA) and gene network analysis (SiGN_BN) were conducted using the TCGA dataset. Next, an in vitro proliferation assay was performed using FANCE-knockdown HCC cell lines (HuH7 and HepG2). The association between mRNA expression of FANCE and that of DNA damage response genes in HCC was analyzed using TCGA and Cancer Cell Line Encyclopedia datasets. Finally, the association between FANCE mRNA expression and overall survival (OS) in various digestive carcinomas was analyzed using TCGA data. Results: FANCE was highly expressed in HCC cells. Multivariate analysis indicated that high FANCE mRNA expression was an independent factor predicting poor OS. GSEA revealed a positive relationship between enhanced FANCE expression and E2F and MYC target gene expression in HCC tissues. FANCE knockdown attenuated the proliferation of HCC cells, as well as reduced cdc25A expression and elevated histone H3 pSer10 expression. SiGN_BN revealed that FANCE mRNA expression was positively correlated with DNA damage response genes (H2A histone family member X and checkpoint kinase 1) in HCC tissues. Significant effects of high FANCE expression on OS were observed in hepatobiliary pancreatic carcinomas, including HCC. Conclusions: FANCE may provide a potential therapeutic target and biomarker of poor prognosis in HCC, possibly by facilitating tumor proliferation, which is mediated partly by cell cycle signaling activation.

Genome profiles of pathologist-defined cell clusters by multiregional LCM and G&T-seq in one triple-negative breast cancer patient

SummaryPathological examination is the gold standard for cancer diagnosis, and breast tumor cells are often found in clusters. We report a case study on one triple-negative breast cancer (TNBC) patient, analyzing tumor development, metastasis, and prognosis with simultaneous DNA and RNA sequencing of pathologist-defined cell clusters from multiregional frozen sections. The cell clusters are isolated by laser capture microdissection (LCM) from primary tumor tissue, lymphatic vessels, and axillary lymph nodes. Data are reported for a total of 97 cell clusters. A combination of tumor cell-cluster clonality and phylogeny reveals 3 evolutionarily distinct pathways for this patient, each associated with a unique mRNA signature, and each correlated with disparate survival outcomes. Hub gene analysis indicates that extensive downregulation of ribosomal protein mRNA is a potential marker of poor prognosis in breast cancer.

PRMT1 enhances oncogenic arginine methylation of NONO in colorectal cancer

Arginine methylation is an important posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs). However, the role of PRMTs in colorectal cancer (CRC) progression is not well understood. Here we report that non-POU domain-containing octamer-binding protein (NONO) is overexpressed in CRC tissue and is a potential marker for poor prognosis in CRC patients. NONO silencing resulted in decreased proliferation, migration, and invasion of CRC cells, whereas overexpression had the opposite effect. In a xenograft model, tumors derived from NONO-deficient CRC cells were smaller than those derived from wild-type (WT) cells, and PRMT1 inhibition blocked CRC xenograft progression. A mass spectrometry analysis indicated that NONO is a substrate of PRMT1. R251 of NONO was asymmetrically dimethylated by PRMT1 in vitro and in vivo. Compared to NONO WT cells, NONO R251K mutant-expressing CRC cells showed reduced proliferation, migration, and invasion, and PRMT1 knockdown or pharmacological inhibition abrogated the malignant phenotype associated with NONO asymmetric dimethylation in both KRAS WT and mutant CRC cells. Compared to adjacent normal tissue, PRMT1 was highly expressed in the CRC zone in clinical specimens, which was correlated with poor overall survival in patients with locally advanced CRC. These results demonstrate that PRMT1-mediated methylation of NONO at R251 promotes CRC growth and metastasis, and suggest that PRMT1 inhibition may be an effective therapeutic strategy for CRC treatment regardless of KRAS mutation status.

High expression of the vacuole membrane protein 1 (VMP1) is a potential marker of poor prognosis in HER2 positive breast cancer.

BackgroundFusion genes result from genomic structural changes, which can lead to alterations in gene expression that supports tumor development. The aim of the study was to use fusion genes as a tool to identify new breast cancer (BC) genes with a role in BC progression.MethodsFusion genes from breast tumors and BC cell lines were collected from publications. RNA-Seq data from tumors and cell lines were retrieved from databanks and analyzed for fusions with SOAPfuse or the analysis was purchased. Fusion genes identified in both tumors (n = 1724) and cell lines (n = 45) were confirmed by qRT-PCR and sequencing. Their individual genes were ranked by selection criteria that included correlation of their mRNA level with copy number. The expression of the top ranked gene was measured by qRT-PCR in normal tissue and in breast tumors from an exploratory cohort (n = 141) and a validation cohort (n = 277). Expression levels were correlated with clinical and pathological factors as well as the patients’ survival. The results were followed up in BC cohorts from TCGA (n = 818) and METABRIC (n = 2509).ResultsVacuole membrane protein 1 (VMP1) was the most promising candidate based on specific selection criteria. Its expression was higher in breast tumor tissue than normal tissue (p = 1x10-4), and its expression was significantly higher in HER2 positive than HER2 negative breast tumors in all four cohorts analyzed. High expression of VMP1 associated with breast cancer specific survival (BCSS) in cohort 1 (hazard ratio (HR) = 2.31, CI 1.27–4.18) and METABRIC (HR = 1.26, CI 1.02–1.57), and also after adjusting for HER2 expression in cohort 1 (HR = 2.03, CI 1.10–3.72). BCSS was not significant in cohort 2 or TCGA cohort, which may be due to differences in treatment regimens.ConclusionsThe results suggest that high VMP1 expression is a potential marker of poor prognosis in HER2 positive BC. Further studies are needed to elucidate how VMP1 could affect pathways supportive of tumorigenesis.

MUC13 promotes the development of colitis-associated colorectal tumors via β-catenin activity.

Many adenocarcinomas, including colorectal cancer (CRC), overexpress the MUC13 cell surface mucin, but the functional significance and mechanisms are unknown. Here, we report the roles of MUC13 in colonic tumorigenesis and tumor progression. High-MUC13 expression is associated with poor survival in two independent patient cohorts. In a comprehensive series of in vivo experiments, we identified a critical role for MUC13 in the development of this malignancy, by promoting survival and proliferation of tumor-initiating cells and driving an immunosuppressive environment that protects tumors from checkpoint inhibitor immunotherapy. In Muc13-deficient mice, fewer tumors are generated after exposure to carcinogens and inflammation, they have markedly reduced β-catenin signaling, have more tumor-infiltrating CD103+ dendritic cells and CD8+ T lymphocytes, fewer myeloid-derived suppressor cells, and are rendered sensitive to checkpoint inhibitor immunotherapy (anti-PD-L1). Mechanistically, we show that MUC13 protects β-catenin from degradation, by interacting with GSK-3β, which increases β-catenin nuclear translocation and promotes its signaling, thereby driving cancer initiation, progression, invasion, and immune suppression. Therefore, MUC13 is a potential marker of poor prognosis in colorectal cancer, and inhibiting MUC13 may be useful in the treatment of colitis-associated cancer and sensitizing tumors to immunotherapy.

Clinical Prognostic Significance of HOXC9 Expression in Patients with Colorectal Cancer

Colorectal cancer (CRC) involves the abnormal expression of a set of genetic and epigenetic genes, which may be useful for predicting prognosis. The transcription factor homeobox C9 (HOXC9) is a member of the homeobox family and participates in diverse cellular metabolic processes. In the current study, the prognostic value of HOXC9 in CRC was evaluated by analyzing public data from The Cancer Genome Atlas. The correlation between clinical features and HOXC9 expression levels was evaluated by logistic regression. Kaplan-Meier and Cox regression was performed to determine the association between HOXC9 expression and patient prognosis. Gene set enrichment analysis was conducted to explore the function of HOXC9 in CRC. HOXC9 showed higher expression in tumor tissue than in normal tissue. An increased level of HOXC9 in CRC was notably associated with an advanced tumor stage (OR = 1.58, for stage I/II vs. stage III/IV, p = 0.037), increased risk of distant metastasis (odds ratio = 1.84, for T1/T2 vs. T3/T4, p = 0.025), and tendency for venous invasion (OR = 2.25, p = 0.003). Kaplan-Meier analysis revealed that higher HOXC9 levels were predictive of poor overall (p = 0.0083) and progression-free survival (p = 0.0014). Multivariate COX regression model analysis proved that HOXC9 was independently associated with overall survival (hazard ratio = 2.88, 95% confidence interval: 1.14 - 7.29, p = 0.025). Gene set enrichment analysis showed that several biological function symbols were particularly enriched in the increased HOXC9 phenotype. HOXC9 may play a critical role in CRC progression and serve as a novel potential marker of poor prognosis in CRC.

MFG-E8 overexpression is associated with poor prognosis in breast cancer patients

BackgroundMFG-E8(Milk fat globule-EGF factor 8), a secreted glycoprotein, plays an exceptional role in various diseases. MFG-E8 overexpression is found in a variety of cancers. However, it remains unclear whether MFG-E8 overexpression is associated with the clinicopathological characteristics and prognosis of human breast cancer. Materials and methodsIn this study, we detected the expression and localization of MFG-E8 protein in breast cancer and cancer-adjacent tissues using immunohistochemical staining, Western blot analysis and immunofluorescence. We analyzed the association between MFG-E8 expression and clinical characteristics and outcomes of breast cancer patients with different HR and HER2 statuses. ResultsOur results confirmed that MFG-E8 expression increased significantly in breast cancer compared with cancer-adjacent tissues by immunohistochemical staining (P < 0.001). Similarly, the Western blot results further confirmed the increased expression of MFG-E8 in breast cancer compared with cancer-adjacent tissues (P = 0.001). Immunofluorescence staining showed that MFG-E8 was mainly localized in the cytoplasm and membrane of tumor cells, consistent with the immunohistochemical staining results. The high expression levels of MFG-E8 showed a greater association with lymph node metastasis, TNM stage and histological grade (P < 0.001). Moreover, high MFG-E8 expression was related to a shortened overall survival (OS) (P < 0.001) and disease-free survival (DFS) (P < 0.001). Bioinformatics analysis with a Kaplan-Meier plotter also demonstrated a strong association of MFG-E8 mRNA overexpression with a short OS and DFS compared with low MFG-E8 expression (P = 0.040, P = 0.005). ConclusionsOur findings indicate that MFG-E8 may be a potential marker for poor prognosis and survival in breast cancer.

Moesin is an independent prognostic marker for ER-positive breast cancer.

Moesin, a cytoskeletal protein belonging to the ezrin-radixin-moesin family serves important roles in cell motility, invasion and metastasis. Moesin has been demonstrated to be of prognostic significance in tumor progression, due to its role in the metastatic process; however, its role in breast cancer is not well characterized. In the present study, the moesin expression was determined using immunohistochemistry in 404 and 46 patients with breast cancer and fibroadenoma, respectively, and the associations between moesin expression and the clinical parameters and prognostic values were analyzed. The positive rate of moesin protein expression was 47.8% (193/404) in breast cancer tissues, which was significantly higher than in fibroadenoma tissues (15.2%, 14/46). Overexpression of moesin was significantly associated with advanced clinical stage (P=0.002), positive lymph node metastasis (P<0.0001), and estrogen receptor (ER; P=0.008) and progesterone receptor (P=0.026) status. Patients with high moesin expression had significantly lower recurrence-free survival time, compared with patient with low moesin expression. Notably, overexpression of moesin was significantly associated with poor prognosis in patients with ER-positive breast cancer, and in patients treated with tamoxifen. Using a Cox proportional hazard regression model, further analysis was conducted, which demonstrated that moesin overexpression was a predictive prognostic factor for reduced overall survival time in patients with ER-positive breast cancer, and in patients treated with tamoxifen. These results indicated that moesin may be a potential marker for poor prognosis in patients with ER-positive breast cancer treated with tamoxifen. In conclusion, moesin serves an important role in the progression of breast cancer, and may be a valuable marker of breast cancer prognosis.

Elevated serum soluble programmed cell death ligand 1 concentration as a potential marker for poor prognosis in small cell lung cancer patients with chemotherapy

BackgroundPotential relationship between serum soluble programmed cell death ligand 1 and prognosis of small cell lung cancer is not well explored. The aim of the study was to reveal the prognostic significance of serum soluble programmed cell death ligand 1 in patients with small cell lung cancer.MethodsA total of 250 small cell lung cancer patients and 250 controls were included. Research information was obtained from their medical records. Blood samples were collected on admission. Serum concentration of programmed cell death ligand 1 was measured using Enzyme-Linked Immunosorbent Assay. The patients underwent cisplatin-etoposide chemotherapy with a maximum of six cycles. Subsequently, they were followed-up for 12 months, and therapeutic response and cancer death were recorded.ResultsSerum concentration of programmed cell death ligand 1 was higher in the patients than in the controls on admission (P < 0.001). After chemotherapy, 112 patients had no response to this therapy. In the 12-month follow up period, 118 patients died due to this cancer. Multivariate Cox regression model revealed that the higher serum concentration of programmed cell death ligand 1 on admission was associated with the higher risk of no response to chemotherapy or cancer caused death (HR: 1.40, 95% CI: 1.05 ~ 1.87; HR: 1.43, 95% CI: 1.08 ~ 1.87).ConclusionElevated serum concentration of soluble programmed cell death ligand 1 might be an independent risk factor for non-response to chemotherapy and cancer caused death in small cell lung cancer patients.

Elevated Serum Exosomal miR-125b Level as a Potential Marker for Poor Prognosis in Intermediate-Risk Acute Myeloid Leukemia

Background: The prognostic significance of miR-125b in intermediate-risk acute myeloid leukemia has not been well investigated. The aim of the study was to reveal the relationship between the elevated exosomal miR-125b level and the poor prognosis in adult patients with this disease. Methods: A total of 154 consecutive patients with intermediate-risk acute myeloid leukemia were enrolled. Exosomes were isolated from blood specimens. The exosomal miR-125b level was determined using quantitative real-time polymerase chain reaction. Patients received standardized therapy and were followed up for 1–24 months. Details about relapse and overall death were recorded. Results: Patients were divided into the high miR-125b level group (n = 77) and the low miR-125b level group (n = 77). In the multivariate Cox proportional hazard regression model, the high miR-125b level group was separately associated with increased risks of relapse and overall death in 2 years (hazard ratio [HR] 2.84, 95% CI 1.81–4.33 and HR 2.69, 95% CI 1.87–4.52). Kaplan-Meier analysis also revealed that a high miR-125b level was related to a higher cumulative relapse and overall death rates (p < 0.001 and p < 0.001, respectively). Conclusion: Circulating exosomal miR-125b concentration might be an independent prognostic indicator in intermediate-risk acute myeloid leukemia patients. An elevated miR-125b level indicated higher risks of relapse and overall death.

Clinical significance of calcium-binding protein S100A8 and S100A9 expression in non-small cell lung cancer.

BackgroundThe purpose of this study was to evaluate the correlation between calcium‐binding protein S100A8 and S100A9 expression in non‐small cell lung cancer (NSCLC) and patients’ clinical features.MethodsFifty‐two NSCLC patients who underwent surgery at Zhejiang Hospital from February 2014 to January 2016 were included in this study. Calcium‐binding protein S100A8 and S100A9 expression patterns in cancer and para‐cancer tissues were examined by immunohistochemistry assay. The correlation between calcium‐binding protein S100A8 and S100A9 expression patterns and NSCLC patients’ clinical characteristics, including age, gender, tumor node metastasis stage, and pathology type, were evaluated.ResultsS100A8 and S100A9 were generally expressed on the cytoplasm and nucleus of NSCLC cells, mainly located in the cytoplasm, stained with brown particles, and distributed evenly. The positive expression rates of S100A8 and S100A9 in cancer tissues were 71.2% and 76.9%, respectively, which were significantly higher than in para‐cancer tissues at 11.5% and 19.2%, respectively, with statistical significance (P < 0.05). S100A8 and S100A9 positive expression was associated with tumor differentiation degree (P < 0.05) but were not correlated with age, gender, smoking history, tumor diameter, pathology type, tumor node metastasis stage, or pleural effusion (P all > 0.05).ConclusionS100A8 and S100A9 positive expression in cancer tissues was significantly higher than in para‐cancer tissues and was correlated with tumor differentiation, which may be a potential marker for poor prognosis.

Elevated Plasma Haptoglobin Level as a Potential Marker for Poor Prognosis in Acute Cerebral Infarction

Background: Relationship between peripheral circulation concentration of haptoglobin (Hp) and risk of cerebrovascular disease has not been well investigated so far. The aim of the study was to reveal the prognostic significance of Hp on acute cerebral infarction. Methods: A total of 200 patients with acute cerebral infarction and 200 controls were included. Research data were collected from their medical records. Blood samples were obtained on admission. Hp phenotyping was performed using a native polyacrylamide gel electrophoresis. Plasma Hp levels were determined using enzyme-linked immunosorbent assays. The patients were followed up yearly, and endpoint was overall death. Results: Plasma levels of Hp were significantly elevated in the patients than in the controls (p < 0.001). Three-year overall death in the follow-up period was associated with the high plasma level of Hp (Hazard ratio [HR] 2.33, 95% CI 1.74–3.12). But, 3-year overall death was not related to Hp phenotyping (Hp 2–1 vs. 1–1: HR 1.07, 95% CI 0.66–1.73; Hp 2–2 vs. 1–1: HR 1.08, 95% CI 0.67–1.74). Conclusion: Peripheral circulation concentration of Hp might be an independent prognostic factor for acute cerebral infarction. But there was no relationship between Hp phenotyping and prognosis in this disease.

Expression of GRK2 and IGF1R in hepatocellular carcinoma: clinicopathological and prognostic significance

AimIt has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study...

The association between the prognosis and the localization and expressionof heparanase in human laryngeal squamous cell carcinoma

Objective:The aim of this study is to explore the expression of heparanase(HPA) in human laryngeal squamous cell carcinoma and its correlation with the clinical pathologic features, such as clinical stage, T grade, lymph node metastasis and cellular differentiation. At the same time, to evaluate the relationship between heparanse localization and expression in human laryngeal squamous cell carcinoma (HLSCC) and tumor prognosis and patients survival. Method: The expression levels of HPA in HLSCC tissues of 73 cases and benign lesions of 38 cases(control) were detected via immunohistochemistry. The correlation of HPA expression with various clinical pathologic features was evaluated with single factor analysis.The Fisher exact test and chisquare tests were used to compare categorical data. Univariate survival was evaluated by KaplanMeier curves and tested using logrank test. Multivariate Cox proportionalhazards regression was used to evaluate independent prognostic factors associated with survival. Result: The positive expression rate of HPA in 73 HLSCC patients and benign lesions of 38 cases were 76.71%（56/73）and 21.05%（8/38）respectively（P<0.05）. The clinical pathologic analysis showed that HPA level had a relationship with the clinical stage, T grade, cellular differentiation and lymph node metastasis(P<0.05), while not with gender, age and clinical types(P>0.05). Survival analysis showed that the patients with high HPA expression had significantly poorer outcome as compared with the patients with low HPA expression. The medium survival time and the 5year survival rate were 24 months and 43.33% in highheparanase group, 56 months and 61.54% in the lowheparanase group and 65 months and 70.59% in the noneheparanse group(P=0.010). The survival was related to clinical stage, T grade, lymph node metastasis, and cellular differentiation(P<0.05), but not with age, sex and clinical types(P>0.05).In multivariate Cox proportionalhazards regression analysis, the results suggested that lymph node metastasis, hepanranase expression level and heparanase localization were independent prognosis factor for HLSCC. Moreover, hepanranase localization correlated with patient outcome. Kaplan Meier analysis demonstrated statistically significantly difference for 5-years overall survival rate between the patients with HPA nuclear staining and the patients with HPA cytoplasmic staining(P<0.05).Conclusion:HPA was related with worse overall survival and could be considered as a potential marker of poor prognosis. Cytoplasmic staining of heparanase inversely correlated with patients survival and predicts poor prognosis, whereas nuclear heparanase predicts a favourable outcome.

Anti–factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study

AbstractNeutralizing autoantibodies against factor VIII (FVIII), also called FVIII inhibitors, are the cause of acquired hemophilia A (AHA). They are quantified in the Bethesda assay or Nijmegen-modified Bethesda assay by their ability to neutralize FVIII in normal human plasma. However, FVIII inhibitors do not represent the whole spectrum of anti-FVIII autoantibodies. Here, we studied isotypes, immunoglobulin G subclasses, and apparent affinities of anti-FVIII autoantibodies to assess their prognostic value for the outcome in AHA. We analyzed baseline samples from patients enrolled in the prospective GTH-AH 01/2010 study. Our data suggest that anti-FVIII immunoglobulin A (IgA) autoantibodies are predictors of poor outcome in AHA. Anti-FVIII IgA-positive patients achieved partial remission similar to anti-FVIII IgA-negative patients but had a higher risk of subsequent recurrence. Consequently, IgA-positive patients achieved complete remission less frequently (adjusted hazard ratio [aHR], 0.35; 95% confidence interval [CI], 0.18-0.68; P < .01) and had a higher risk of death (aHR, 2.62; 95% CI, 1.11-6.22; P < .05). Anti-FVIII IgA was the strongest negative predictor of recurrence-free survival after achieving partial remission and remained significant after adjustment for baseline demographic and clinical characteristics. In conclusion, anti-FVIII IgA represents a potential novel biomarker that could be useful to predict prognosis and tailor immunosuppressive treatment of AHA.