Prognostic importance of systemic inflammation and insulin resistance in patients with cancer: a prospective multicenter study.

BACKGROUND: Systemic inflammation and insulin resistance (IR) are often associated with poor prognosis in cancer. This study aimed to investigate the prognostic value of surrogate systemic inflammation and IR indices in patients with cancer. METHODS: This multicenter prospective study included 5,221 patients with cancer, with a mean age of 59.41±11.15 years, of whom 3,061 (58.6%) were male. The surrogate IR indices included low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LHR) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/ HDL-c) ratio, triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and fasting triglyceride glucose (TyG). Prognostic receiver operator characteristic (ROC) curves and C-indices were used to select a better surrogate IR index in patients with cancer. The prognostic value of the indicators was evaluated using univariate and multivariate survival analyses. RESULTS: In this study, the median survival time of patients was 44.5 (40.5-51.4) months, and the overall mortality in the 12-month period was 1,115 (53.7%), with 196 mortality events per 1,000 patient-years of patients' follow-up. The prognostic ROC curve and C-index suggested that the prognostic value of LHR was better than that of the other IR indices. The multivariate-adjusted hazard ratios (HRs) for overall survival (OS) were higher in patients with high C-reactive protein (CRP) (HR, 1.51; 95% confidence interval [CI]: 1.38-1.65) and high LHR (HR, 1.20; 95% CI: 1.06-1.37), respectively. The mortality rate of patients with both high CRP and LHR was 1.75-fold higher than that of patients with both low CRP and LHR. CONCLUSION: Both CRP and LHR showed good survival predictions in patients with cancer. CRP combined with LHR can improve the predictive power of patients with cancer.

Oncogene PLCE1 may be a diagnostic biomarker and prognostic biomarker by influencing cell cycle, proliferation, migration, and invasion ability in hepatocellular carcinoma cell lines.

Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real-time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan-Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC-M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p < .05). The diagnostic value of PLCE1 was validated with the datasets (all p < .01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse-free survival (both p < .05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤ .05). The oncogene PLCE1 was differentially expressed in HCC and non-HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.

The diagnosis and prognosis values of WNT mRNA expression in colon adenocarcinoma.

WNT family genes have participated in the progression and development of many cancers, however, the association between colon adenocarcinoma (COAD) and WNTs have been rarely reported. This study investigated the significance of WNT genes expression in COAD from the standpoint of diagnosis and prognosis. The RNA-sequencing dataset of COAD was downloaded from The Cancer Genome Atlas and University of California, Santa Cruz Xena browser. The biology functions of WNT genes were investigated by biological analysis. Biological analysis of WNT family genes indicated that WNT genes were noticeably enriched in the complex process of WNT signaling pathway. The Pearson correlation analysis suggested WNT1 and WNT9B had a strong correlation. And receiver operating characteristic curves suggested that most of the genes could serve as a significant diagnostic makers in COAD (P < .05), especially WNT2 and WNT7B had high diagnostic values that the area under curve were 0.997 (95% confidence interval [0.994-1.000]) and 0.961 (95%CI [0.939-0.983]), respectively. And our multivariate survival analysis suggested the downregulated of WNT10B (P < .05) showed a favor prognosis in COAD overall survival. And the risk score model predicted that the upregulated expression of WNT10B might increase the risk of death. The very study we had conducted suggested that WNT genes had a certain connection with the diagnosis and prognosis of COAD. The messenger RNA expression of WNT2 and WNT7B might become potentially diagnostic biomarkers, and WNT10B might serve as an independent prognosis indicator for COAD.

Use of Genome-Scale Integrated Analysis to Identify Key Genes and Potential Molecular Mechanisms in Recurrence of Lower-Grade Brain Glioma.

BACKGROUND The aim of this study was to identify gene signals for lower-grade glioma (LGG) and to assess their potential as recurrence biomarkers. MATERIAL AND METHODS An LGG-related mRNA sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA) Informix. Multiple bioinformatics analysis methods were used to identify key genes and potential molecular mechanisms in recurrence of LGG. RESULTS A total of 326 differentially-expressed genes (DEGs), were identified from 511 primary LGG tumor and 18 recurrent samples. Gene ontology (GO) analysis revealed that the DEGs were implicated in cell differentiation, neuron differentiation, negative regulation of neuron differentiation, and cell proliferation in the forebrain. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database suggests that DEGs are associated with proteoglycans in cancer, the Wnt signaling pathway, ECM-receptor interaction, the PI3K-Akt signaling pathway, transcriptional deregulation in cancer, and the Hippo signaling pathway. The hub DEGs in the protein-protein interaction network are apolipoprotein A2 (APOA2), collagen type III alpha 1 chain (COL3A1), collagen type I alpha 1 chain (COL1A1), tyrosinase (TYR), collagen type I alpha 2 chain (COL1A2), neurotensin (NTS), collagen type V alpha 1 chain (COL5A1), poly(A) polymerase beta (PAPOLB), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and anomalous homeobox (ANHX). GSEA revealed that the following biological processes may associated with LGG recurrence: cell cycle, DNA replication and repair, regulation of apoptosis, neuronal differentiation, and Wnt signaling pathway. CONCLUSIONS Our study demonstrated that hub DEGs may assist in the molecular understanding of LGG recurrence. These findings still need further molecular studies to identify the assignment of DEGs in LGG.

Association of HLA-B27 with ankylosing spondylitis and clinical features of the HLA-B27-associated ankylosing spondylitis: a meta-analysis.

Many studies have estimated the correlation between HLA-B27 polymorphisms and ankylosing spondylitis (AS). However, the results were controversial. Therefore, we performed this meta-analysis to determine the association of HLA-B*27 polymorphisms with AS and investigate the impacts of HLA-B27 on the clinical symptoms of AS patients. A comprehensive search was performed in PubMed, Web of Science and Embase databases to retrieve the eligible studies, which addressed the association between HLA-B27 polymorphisms and AS susceptibility. The correlation in fixed-effect model was estimated using the relative risk (RR) and 95% confidence intervals (CI). Finally, 41 studies were included in this meta-analysis, among which 35 studies were used to analyze the correlation between HLA-B27 and AS. And 11 studies were applied to estimate the effects of HLA-B27 on the clinical characteristics of AS patients. Besides, our meta-analysis was composed of 8993 AS patients and 19,254 healthy controls. The results suggested that HLA-B27, HLA-B27*02 and HLA-B27*04 were positively in relation to AS (RRHLA-B27 (95% CI) 16.02 (13.85, 18.54), P < 0.001; RRHLA-B*2702 (95% CI) 1.28 (1.08, 1.53), P = 0.005; RRHLA-B27*04 (95% CI) 1.14 (1.01, 1.29), P = 0.041). Moreover, positive association was observed between HLA-B27 and sex (male) [RR (95% CI) 1.10 (1.05, 1.15), P < 0.001], family history [RR (95% CI) 1.10 (1.06, 1.140), P < 0.001], uveitis [RR (95% CI) 1.07 (1.03, 1.11), P < 0001], peripheral joint involvement [RR (95% CI) 1.04 (1.01,1.07), P = 0.013] and hip joints involvement [RR (95% CI) 1.06 (1.02, 1.10), P = 0.003]. In addition, we also found that HLA-B27*04 showed association with peripheral joint involvement [RR (95% CI) 1.13 (1.05-1.23), P = 0.002]. In conclusion, the current meta-analysis indicates that HLA-B27, especially, its subtypes (HLA-B27*02 and HLA-B27*04) may be potential risk factors for AS.

The prognostic and immunological role of MCM3 in pan-cancer and validation of prognosis in a clinical lower-grade glioma cohort.

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

Inflammatory geriatric nutritional risk index stratified the survival of older adults with cancer sarcopenia.

BACKGROUND: Aging is accompanied by muscle loss. In older adults with cancer sarcopenia (OACS), systemic inflammation, reduced food intake, and reduced physical activity led to a poor prognosis. This study was to investigate the prognostic ability of the inflammatory Geriatric Nutritional Risk Index (GNRI), which combines patient's inflammation, diet status, and physical activity status to predict overall survival of OACS. METHODS: This prospective multi-center study enrolled 637 OACS, with an average age of 72.78 ± 5.98 years, of which 408 (64.1%) were males. We constructed the Inflammatory Functional Prognostic Index (IFPI) of OACS based on inflammatory GNRI scores, reduced food intake, and reduced physical activity. According to the IFPI, OACS was divided into high-, moderate-, and low-risk groups. Univariate and multivariate survival analyses analyzed the prognostic ability of the clinical parameters. RESULTS: Compared with OACS with a high GNRI score, the 1-, 3-, and 5-year hazard ratios (95% confidence interval) of OACS with a low GNRI score was 1.816 (1.076-3.063), 1.678 (1.118-2.518), and 1.627 (1.101-2.407), respectively. This result was consistent with that of the calibration curve. The subgroup analysis showed that the low GNRI score had a significant positive relation with patients with gastrointestinal cancer (Pinteraction < 0.001). Notably, the survival analysis of IFPI showed that the mortality risk of moderate- and high-risk patients was 1.722-and 2.509-fold higher, respectively, than that of low-risk patients. CONCLUSION: The GNRI score was a short-term and long-term inflammatory prognostic indicator for OACS. The IFPI score could improve patient survival prediction.

Impact of oral care with versus without toothbrushing on the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Ventilator-associated pneumonia (VAP) remains a common hazardous complication in mechanically ventilated patients and is associated with increased morbidity and mortality. We undertook a systematic review and meta-analysis of randomized controlled trials to assess the effect of toothbrushing as a component of oral care on the prevention of VAP in adult critically ill patients. METHODS: A systematic literature search of PubMed and Embase (up to April 2012) was conducted. Eligible studies were randomized controlled trials of mechanically ventilated adult patients receiving oral care with toothbrushing. Relative risks (RRs), weighted mean differences (WMDs), and 95% confidence intervals (CIs) were calculated and heterogeneity was assessed with the I(2) test. RESULTS: Four studies with a total of 828 patients met the inclusion criteria. Toothbrushing did not significantly reduce the incidence of VAP (RR, 0.77; 95% CI, 0.50 to 1.21) and intensive care unit mortality (RR, 0.88; 95% CI, 0.70 to 1.10). Toothbrushing was not associated with a statistically significant reduction in duration of mechanical ventilation (WMD, -0.88 days; 95% CI, -2.58 to 0.82), length of intensive care unit stay (WMD, -1.48 days; 95% CI, -3.40 to 0.45), antibiotic-free day (WMD, -0.52 days; 95% CI, -2.82 to 1.79), or mechanical ventilation-free day (WMD, -0.43 days; 95% CI, -1.23 to 0.36). CONCLUSIONS: Oral care with toothbrushing versus without toothbrushing does not significantly reduce the incidence of VAP and alter other important clinical outcomes in mechanically ventilated patients. However, the results should be interpreted cautiously since relevant evidence is still limited, although accumulating. Further large-scale, well-designed randomized controlled trials are urgently needed.

Immune ULBP1 is Elevated in Colon Adenocarcinoma and Predicts Prognosis.

Background: Colon adenocarcinoma (COAD) is still the main cause of cancer deaths worldwide. Although immunotherapy has made progress in recent years, there is still a need to improve diagnosis, prognosis, and treatment tools. UL-16 binding protein 1 (ULBP1) is a ligand that activates the receptor natural killer cell group 2 receptor D (NKG2D) and plays an important immunomodulatory role. We aimed to investigate the clinical significance of ULBP1 in COAD. Methods: We obtained the relevant data from The Cancer Genome Atlas (TCGA). A total of 438 patients with COAD were included in this study, with a mean age of 67.1 ± 13.03 years old, of which 234 (53.42%) were male. The diagnostic value of COAD tumor tissues and adjacent tissues was analyzed by ROC curve. Univariate and multivariate survival analysis investigated the prognostic value of ULBP1 gene, and Gene Set Enrichment Analysis (GSEA) curve was performed to analyze the biological process and enriched enrichment pathway of ULBP1 in COAD. Combination survival analysis investigated the combined prognostic effect of prognostic genes. Results: ULBP1 gene had a high diagnostic value in COAD [AUC (TCGA) = 0.959; AUC (Guangxi) = 0.898]. Up-regulated ULBP1 gene of patients with COAD predicted a worse prognosis compared to those patients with down-regulated ULBP1 gene (Adjusted HR = 1.544, 95% CI = 1.020-2.337, p = 0.040). The GSEA showed that ULBP1 was involved in the apoptotic pathway and biological process of T cell mediated cytotoxicity, regulation of natural killer cell activation, and T cell mediated immunity of COAD. The combination survival analysis showed that the combination of high expression of ULBP1, AARS1, and DDIT3 would increase the 2.2-fold death risk of COAD when compared with those of low expression genes. Conclusion: The immune-related ULBP1 gene had diagnostic and prognostic value in COAD. The combination of ULBP1, AARS1, and DDIT3 genes could improve the prognostic prediction performance in COAD.

A Novel Inflammation and Insulin Resistance Related Indicator to Predict the Survival of Patients With Cancer.

Background: Systemic inflammation and insulin resistance (IR) are closely related in patients with cancer. However, there is no relevant indicator that combines inflammation and IR to predict patient prognosis. Therefore, this study aimed to develop and validate a novel inflammation- and IR-related marker in patients with cancer. Methods: The total cohort of this study included 5221 patients with cancer, and the training and validation cohorts were randomized in a 7:3 ratio. C-reactive protein (CRP) and fasting triglyceride glucose (TyG) were used to reflect patients' inflammation and IR status, respectively. The CRP-TyG index (CTI) was composed of CRP and TyG. The concordance (C)-index, receiver operator characteristic (ROC) curve, and calibration curve reflected the prognostic predictive power of CTI. Univariate and multivariate survival analyses predicted the prognostic value of CTI in patients with cancer. Results: The C-indices of CTI in patients with cancer were 0.636, 0.617, and 0.631 in the total, training, and validation cohorts, respectively. The 1-, 3-, and 5-year ROC and calibration curves showed that CTI had a good predictive ability of survival in patients with cancer. Meanwhile, patients with high CTI had a worse prognosis compared to patients with low CTI (total cohort: hazard ratio [HR] = 1.46, 95% confidence interval [95% CI] = 1.33-1.59; training cohort: HR = 1.36, 95% CI = 1.22-1.52; validation cohort: HR = 1.73, 95% CI = 1.47-2.04]. Conclusion: The CTI is a useful prognostic indicator of poor prognosis and a promising tool for treatment strategy decision-making in patients with cancer.

A Novel Systemic Inflammation Prognostic Score to Stratify Survival in Elderly Patients With Cancer.

Background: Elderly patients with cancer face the challenge of systemic inflammation, which can lead to a poor prognosis. Existing inflammatory indices cannot fully reflect the immune-inflammatory status of patients. This study aimed to develop a new scoring system to predict the survival of elderly patients with cancer using inflammatory indices, namely, the systemic inflammation prognostic score (SIPS). Materials and Methods: This prospective multicenter study included a total of 1,767 patients with cancer, with a mean age of 70.97 ± 5.49 years, of whom 1,170 (66.2%) were men. We performed the least absolute shrinkage and selection operator (LASSO) regression to screen inflammatory indicators to include in constructing SIPS. Prognostic analysis of SIPS was performed using univariate and multivariate survival analyzes. The prognostic value of SIPS and its components were compared using the prognostic receiver operating characteristic curve and concordance index. The population was divided into the training cohort and the validation cohort in a 7:3 ratio and a SIPS prognostic analysis was performed. Results: The LASSO regression selected C-reactive protein (CRP) (≤ 9.81, "0"; > 9.81, "1"), geriatric nutritional risk index (GNRI) (≤ 93.85, "1"; 93.85, "0"), advanced lung cancer inflammation index (ALI) (≤ 23.49, "1"; > 23.49, "0"), and lymphocyte to C-reactive protein ratio (LCR) (≤ 2523.81, "1"; > 2523.81, "0") to develop SIPS. Patients were divided into the three groups based on the total SIPS: low-risk (0), moderate-risk (1-2), and high-risk (3-4). On the multivariate survival analysis, patients in the moderate-risk [P < 0.001, hazard ratio (HR) = 1.79, 95% CI: 1.47-2.17] and high-risk groups (P < 0.001, HR = 2.40, 95% CI: 1.98-2.92) showed a worse prognosis than those in the low-risk group. The total cohort, training cohort, and validation cohort all showed that SIPS had better survival prediction than CRP, GNRI, ALI, and LCR. The HRs were 2.81 times higher in patients in the high-risk group with malnutrition than in patients in the low-risk group without malnutrition. Conclusion: SIPS was an independent prognostic indicator in elderly patients with cancer. Malnutrition in the high-risk group increased the mortality risk.

Association of systemic inflammation and low performance status with reduced survival outcome in older adults with cancer.

BACKGROUND: Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). METHODS: We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. RESULTS: The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p < 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p < 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). CONCLUSION: LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

Investigation and verification of the clinical significance and perspective of natural killer group 2 member D ligands in colon adenocarcinoma.

This study investigated and verified the diagnostic and prognostic values of natural killer group 2 member D ligand (NKG2DL) genes in colon adenocarcinoma (COAD). We downloaded NKG2DLs expression data and corresponding clinical parameters from The Cancer Genome Atlas (TCGA) and used bioinformatics techniques to investigate the values of NKG2DLs in COAD. Then, we used the GSE40967 cohort to verify the prognostic value of NKG2DLs. Finally, we verified the ULBP2 expression level in tissues, and also investigated the diagnostic and prognostic values of ULBP2 in COAD. The diagnostic receiver operating characteristic curves showed that ULBP1, ULBP2, ULBP3, and RAET1L had high diagnostic values in COAD [Area Under Curve (AUC) > 0.9]. In TCGA cohort, the univariate and multivariate survival analyses suggested that ULBP2 was correlated with the prognosis of COAD recurrence-free survival (RFS) and overall survival (OS). In GSE40967 cohort, ULBP2 was associated with CC RFS and OS. Reverse transcription-quantitative polymerase chain reaction and immunohistochemistry results showed that ULBP2 was highly expressed in COAD tumor tissues (P < 0.05) and both had diagnostic values (AUC > 0.7). Validated survival analysis showed that the high expression of ULBP2 had a worse prognosis in COAD OS and RFS. Thus, ULBP2 might be an independent diagnostic and prognostic biomarker of COAD.

Diagnosis and prognostic value of C-X-C motif chemokine ligand 1 in colon adenocarcinoma based on The Cancer Genome Atlas and Guangxi cohort.

Objective: The objective was to identify and validate C-X-C motif chemokine ligand 1(CXCL1) for diagnosis and prognosis in colon adenocarcinoma (COAD). Methods: Our current study had enrolled one The Cancer Genome Atlas (TCGA) cohort and two Guangxi cohorts to identify and verify the diagnostic and prognostic values of CXCL1 in COAD. Functional enrichment was performed by gene set enrichment analysis (GSEA). Results: In TCGA cohort, the expression of CXCL1 was significantly up-regulated in tumor tissues and decreased as the tumor stage developed. The receiver operating characteristic (ROC) curve showed that CXCL1 had a high diagnostic value for COAD. The result of Kaplan-Meier survival analysis showed that CXCL1 gene expression (P=0.045) was significantly correlated with overall survival (OS) of COAD. Results of Guangxi cohort also verified the diagnostic value of CXCL1 in COAD, and sub-group survival analyses also suggested that patients with high CXCL1 expression were related to a favorable OS (Corrected P=0.005). GSEA revealed that CXCL1 high expression phenotype was related to cytokine activity, cell apoptosis, P53 regulation pathway, and regulation of autophagy in COAD. Conclusions: In this study, we found that CXCL1 gene might be a potential diagnostic biomarker for COAD, and might serve as a prognostic biomarker for specific subgroup of COAD.

Distinct diagnostic and prognostic values of γ-aminobutyric acid type A receptor family genes in patients with colon adenocarcinoma.

In the present study, the significance of GABAA genes in colon adenocarcinoma (COAD) were investigated from the view of diagnosis and prognosis. All data were achieved from The Cancer Genome Atlas. Overall survival was analyzed by the Kaplan-Meier analyses and Cox regression model and the hazard ratios and 95% confidence interval were calculated for computation. The Database for Annotation, Visualization and Integrated Discovery, and the Biological Networks Gene Ontology (BiNGO) softwares were applied to assess the biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway analysis to predict the biological function of GABAA genes. The associated Gene Ontology and KEGG pathways were conducted by Gene Set Enrichment Analysis (GSEA). From receiver operating characteristics curves analysis, it was found that the expression of GABR, γ-aminobutyric acid type A receptor GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRG3, GABRD, GABRE were correlated with COAD occurrence [P<0.0001, area under the curve (AUC)>0.7]. The low expression of the GABRB1, GABRD, GABRP and GABRQ in genes after tumor staging adjustment were positively correlated with the overall survival rate [P=0.049, hazard ratio (HR)=1.517, 95% confidence interval (CI)=1.001-2.297; P=0.006, HR=1.807, 95% CI=1.180-2.765; P=0.005, HR=1.833, 95% CI=1.196-2.810; P=0.034, HR=1.578, 95% CI=1.036-2.405). GSEA showed enrichment of cell matrix adhesion, integrin binding, angiogenesis, endothelial growth factor and endothelial migration regulation in patients with COAD with GABRD overexpression. GABRB1, GABRD, GABRP and GABRQ were associated with the prognostic factors of COAD. The expression levels of GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRD and GABRE may allow differentiation between tumor tissues and adjacent normal tissues.

The Perspective of Diagnostic and Prognostic Values of Lipoxygenases mRNA Expression in Colon Adenocarcinoma.

BACKGROUND: This study was mainly to explore and study the potential application of lipoxygenases (ALOX) family genes in the diagnostic and prognostic values of colon adenocarcinoma (COAD). METHODS: Data sets related to the ALOX genes of COAD were obtained from The Cancer Genome Atlas and the University of California, Santa Cruz Xena browser. Then, the relevant biological information was downloaded from the public data platform. Finally, the bioinformatics technologies and clinical verification were employed to comprehensively analyze the potential values of ALOX genes. RESULTS: The Pearson correlation analysis indicated that there were correlations among ALOXE3, ALOX5, ALOX12, and ALOX12B. The diagnostic receiver operating characteristic (ROC) curves suggested that ALOXE3 and ALOX12 had significant diagnosis in COAD: ALOXE3; P<0.001, area under curve (AUC) 95%CI:=0.818 (0.773-0.862) and ALOX12; P<0.001, AUC 95%CI=0.774 (0.682-0.807). Besides, the verification study indicated that ALOX12 had a diagnostic value in COAD. Finally, our multivariate survival analysis and comprehensive prognosis of ALOX genes in COAD suggested that the ALOXE3 and ALOX12 were associated with COAD overall survival: ALOXE3; P=0.025, HR 95%CI=1.765 (1.074-2.901), ALOX12; P=0.046, HR 95%CI=1.680 (1.009-2.796), and the low expression of ALOXE3 and ALOX12 had a favorable prognosis of COAD (all P<0.05); on the contrary, the high regulation of them increased the risk of death. CONCLUSION: In our study, we observed that the mRNA expressions of ALOX genes were associated with the diagnosis and prognosis of COAD. The results of the diagnostic analysis suggested that ALOX12 might have a diagnosis value in COAD. Besides, our comprehensive prognosis analysis indicated that ALOXE3 combined ALOX12 might serve as potential prognosis biomarkers for COAD.

Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy.

Objective: The goal of our current study is to assess the immunohistochemical of p53, p21, nm23, and VEGF expression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) prognosis after hepatectomy, as well as the prospective molecular mechanisms of prognostic indicator. Methods: There were 419 HBV-related HCC patients who were from southern China of Guangxi province and were used to evaluate the immunohistochemical expression for these biomarkers in prognosis. A genome-wide expression microarray dataset of HBV-related HCC were obtained from GSE14520. Results: In our study, the expression of p53, p21, and nm23 in cancer tissues of patients with hepatitis B-related hepatocellular carcinoma did not affected the clinical outcome of 2 years, 5 years or overall. Patients with high expression of VEGF had a worse overall survival after 2 years of surgery than patients with low expression (adjusted P=0.040, adjusted HR = 1.652, 95% CI = 1.024-2.665). Survival analysis of VEGF in GSE14520 cohort also demonstrated that VEGF mRNA expression also significantly associated with HBV-related HCC OS (adjusted P=0.035, adjusted HR =1.651, 95% CI =1.035-2.634). The prospective molecular mechanisms by co-expression analysis suggested that VEGF might be correlated to regulation of cell proliferation, cell growth and apoptotic process, Rap1 signaling pathway, HIF-1 signaling pathway, PPAR signaling pathway, cell cycle. Whereas the GSEA suggested that VEGF might involve in the regulation of HIF and HIF1A pathway, and TP53 regulation pathway. Conclusion: Our findings suggested that VEGF might be a prognostic indicator of HBV-related HCC, and we also identified the VEGF prospective molecular mechanisms through the whole genome co-expression and GSEA approaches.

The prognostic value of the postoperative serum CEA levels/preoperative serum CEA levels ratio in colorectal cancer patients with high preoperative serum CEA levels.

PURPOSE: This study aimed to assess the prognostic value of the postoperative serum carcinoembryonic antigen (CEA) levels/preoperative serum CEA levels ratio (CEA ratio) in colorectal cancer (CRC) patients with high preoperative serum CEA levels and to identify the optimal prognostic cutoff value. PATIENTS AND METHODS: The medical records of 187 CRC patients in a single center who underwent surgery between September 2012 and September 2014 were retrospectively reviewed. CEA ratio was defined as the ratio between the postoperative serum CEA and preoperative serum CEA. The optimal cutoff values for the CEA ratio were determined by time-dependent receiver operating characteristic (ROC) curve analyses. The Chi-square test or Fisher's exact probability test were used to test the correlation between CEA ratio and clinicopathological characteristics. Univariate, multivariate, and subgroup Cox proportional hazards analysis were used to identify independent prognostic factors. Kaplan-Meier method was used for establishing survival curves. RESULTS: The median follow-up time was 62 months (range 3-88 months). The optimal CEA ratio cutoff value closely related to disease-free survival was 0.295. In the Chi-square test, the CEA ratio was associated with pN stage (p=0.003) and postoperative CEA (p<0.001). In the multivariate analysis, the CEA ratio was an independent prognostic factor for disease-free survival (p=0.003, HR 2.300 [95% CI: 1.326-3.988]) and cancer-special survival (p=0.003, HR 2.525 [95% CI: 1.381-4.614]). The CEA ratio reflected the prognosis of CRC patients more accurately than postoperative CEA levels alone, and the CEA ratio of 0.295 was more likely to reflect the prognosis than other cutoff values. CONCLUSION: The CEA ratio is a simple and useful tool for further forecasting the prognosis of CRC patients with high preoperative CEA levels and may help develop strategies for the postoperative treatment of CRC patients.

Diagnostic and prognostic values of integrin α subfamily mRNA expression in colon adenocarcinoma.

The integrin α (ITGA) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in colon adenocarcinoma (COAD) remain elusive. The present study investigated the significance of the expression of ITGA genes in COAD from the perspective of diagnosis and prognosis. A COAD RNA­sequencing dataset was obtained from The Cancer Genome Atlas. The present study investigated the biological function of the ITGA subfamily genes through bioinformatics analysis. Reverse transcription­quantitative polymerase chain reaction was applied to investigate the distribution of integrin α8 (ITGA8) expression in COAD tumors and adjacent normal tissues. Bioinformatics analysis indicated that ITGA genes were noticeably enriched in cell adhesion and the integrin­mediated signaling pathway, and co­expressed with each other. It was also revealed through observation that the majority of gene expression was significantly low in tumor tissues (P<0.05), and diagnostic receiver operating characteristic curves revealed that most of the genes could serve as significant diagnostic markers in COAD (P<0.05), especially ITGA8 which had a high diagnostic value with an area under curve (AUC) of 0.989 [95% confidence interval (CI) 0.980­0.997] in COAD (P<0.0001). In addition, ITGA8 expression was verified in clinical samples and it was revealed that it was higher in adjacent normal tissues (P=0.041) compared to COAD tissues, and the AUC was 0.704 (95% CI, 0.577­0.831; P<0.0085). Multivariate survival analysis indicated that integrin α (ITGA5) may be an independent prognostic indicator for COAD overall survival. Gene set enrichment analysis indicated that ITGA5 may participate in multiple biological processes and pathways. The present study revealed that ITGA genes were associated with the diagnosis and prognosis of COAD. The mRNA expression of ITGA8 may be a potential diagnosis biomarker and ITGA5 may serve as an independent prognosis indicator for COAD.