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.

Association between novel genetic variants of Notch signaling pathway genes and survival of hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)-related HCC. METHODS: In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway-related genes and overall survival (OS) of 866 patients with HBV-related HCC. RESULTS: It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV-related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose-response manner (ptrend <0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (p = 0.002) and from 72.04% to 74.76 (p = 0.004) for 3-year and 5-year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of NEURL1B in the whole blood (p = 1.71 × 10-3), while the rs1990975 T allele was correlated with higher mRNA expression levels of FCER2 in the whole blood and normal liver tissues (p = 3.51 × 10-5 and 0.033, respectively). CONCLUSIONS: Three potentially functional SNPs of NEURL1B, CNTN1 and FCER2 may serve as potential prognostic biomarkers for HBV-related HCC.

Genome-wide RNA-sequencing dataset reveals AC096751.1 sever as a novel prognostic long non-coding RNA and its potential molecular mechanisms in patients with colon adenocarcinoma.

Objective: Through data analysis, we observed that AC096751.1 is markedly imbalance between colon adenocarcinoma (COAD) cancer and paracancerous tissues. However, the prognostic value and potential molecular mechanism of AC096751.1 in COAD are still unclear. Methods: Whole genome RNA-sequencing datasets of The Cancer Genome Atlas (TCGA) COAD cohort were collected into current study, comprehensive survival analysis and bioinformatics function enrichment analysis approaches were apply to explore the clinical outcome and molecular mechanisms of AC096751.1 in COAD. Results: In current study, we found that AC096751.1 is markedly down-regulated in COAD cancer tissues (log2 fold change =2.303, P<0.0001, false discovery rate <0.0001), and can be serve as a biomarker to distinguish COAD cancer and paracancerous tissues [area under curve=0.9518, 95% confidence interval (CI)=0.9261-0.9776]. Survival analysis suggests that low expression of AC096751.1 is connected with poor clinical outcome of COAD, and can serve as a novel prognostic indicator (log-rank P=0.016, adjusted P=0.005, hazard ratio=0.548, 95% CI=0.360-0.836). Bioinformatics function enrichment analysis suggests that the molecular mechanism of AC096751.1 in COAD may include participation in cell adhesion, cell proliferation, mitogen-activated protein kinase kinase (MAPKK), MAPK, janus-activated kinase-singal transducers and activators of transcriprion cascade, Erk1 and Erk 2 cascade, and nuclear factor-kappa B pathway. Tumor microenvironment and immune infiltration analysis indicates that COAD patients with different AC096751.1 expression have significant variation in tumor immune background. Conclusion: The present study found that AC096751.1 is significantly differentially expressed in COAD and can be serve as a novel prognostic biomarker.

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.

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.

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.

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.

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.

Expression and Clinical Significance of Origin Recognition Complex Subunit 6 in Breast Cancer - A Comprehensive Bioinformatics Analysis.

OBJECTIVE: We aimed to investigate the expression, diagnostic and prognostic values, and potential molecular mechanisms of the origin recognition complex (ORC) in breast cancer (BC). METHODS: Kaplan-Meier estimation was used to assess the prognostic value of ORC genes, and Oncomine, TCGA, GEO and ULCAN databases were used to analyze their expression in BC. Wilcoxon rank-sum tests were used to evaluate the relationship between ORC gene expression levels and BC clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of ORC genes in BC. Survival analysis was performed using Kaplan-Meier estimation and Cox regression. A nomogram was constructed to predict 1-, 3-, and 5-year survival probabilities in BC. Gene set enrichment analysis (GSEA) and immune infiltration were used to investigate potential molecular mechanisms of the ORC. RESULTS: ORC1L and ORC6L were highly expressed in BC compared with healthy tissue, while ORC5L expression patterns were inconsistent; no significant differences in ORC2L, ORC3L or ORC4L expression were observed between BC and healthy tissues. ORC1L and ORC6L expression levels were significantly correlated with age, tumor (T) stage and molecular subtype; ORC5L expression was significantly correlated with age and number of nearby lymph nodes with cancer (N stage). ORC6L expression had the highest diagnostic value in BC and was an independent prognostic factor for poor overall survival (OS). ORC6L may be involved in cell cycle progression and may regulate cancer signaling pathways, including NF-κB, P53, and WNT, in BC. ORC6L expression was also associated with immune infiltration. CONCLUSION: ORC1L and ORC6L are highly expressed in BC; ORC6L has a high diagnostic value and is an independent prognostic factor for poor OS. ORC6L may be involved in the initiation and progression of BC by regulating cell cycle progression, promoting cancer signaling pathway activation, and influencing tumor immune cell infiltration.

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.

Integrative Analysis of a Novel Eleven-Small Nucleolar RNA Prognostic Signature in Patients With Lower Grade Glioma.

OBJECTIVE: The present study used the RNA sequencing (RNA-seq) dataset to identify prognostic snoRNAs and construct a prognostic signature of The Cancer Genome Atla (TCGA) lower grade glioma (LGG) cohort, and comprehensive analysis of this signature. METHODS: RNA-seq dataset of 488 patients from TCGA LGG cohort were included in this study. Comprehensive analysis including function enrichment, gene set enrichment analysis (GSEA), immune infiltration, cancer immune microenvironment, and connectivity map (CMap) were used to evaluate the snoRNAs prognostic signature. RESULTS: We identified 21 LGG prognostic snoRNAs and constructed a novel eleven-snoRNA prognostic signature for LGG patients. Survival analysis suggests that this signature is an independent prognostic risk factor for LGG, and the prognosis of LGG patients with a high-risk phenotype is poor (adjusted P = 0.003, adjusted hazard ratio = 2.076, 95% confidence interval = 1.290-3.340). GSEA and functional enrichment analysis suggest that this signature may be involved in the following biological processes and signaling pathways: such as cell cycle, Wnt, mitogen-activated protein kinase, janus kinase/signal transducer and activator of tran-ions, T cell receptor, nuclear factor-kappa B signaling pathway. CMap analysis screened out ten targeted therapy drugs for this signature: 15-delta prostaglandin J2, MG-262, vorinostat, 5155877, puromycin, anisomycin, withaferin A, ciclopirox, chloropyrazine and megestrol. We also found that high- and low-risk score phenotypes of LGG patients have significant differences in immune infiltration and cancer immune microenvironment. CONCLUSIONS: The present study identified a novel eleven-snoRNA prognostic signature of LGG and performed a integrative analysis of its molecular mechanisms and relationship with tumor immunity.

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.

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.

Clinical implications and nomogram prediction of long noncoding RNA FRGCA as diagnostic and prognostic indicators in colon adenocarcinoma.

Colorectal cancer, especially colon adenocarcinoma (COAD), is associated with significant morbidity and mortality worldwide. Long noncoding RNA (lncRNA) has been implicated in tumorigenesis. The aim of the present study was to elucidate the potential diagnostic and prognostic values of lncRNA FRGCA in COAD.The data of 438 COAD patients were retrieved for analysis. Diagnostic significance was evaluated using tumor and nontumor tissues. Prognostic significance was evaluated using a Cox proportional regression model. Stratified analysis was performed to identify associations between clinical factors and lncRNA FRGCA expression. A nomogram was constructed using the clinical factors and lncRNA FRGCA for survival prediction. Enrichment analysis identified gene ontologies and metabolic pathways of mRNAs with high Pearson correlation coefficients with lncRNA FRGCA.lncRNA FRGCA was highly expressed in tumor tissues of COAD and demonstrated diagnostic value (area under curve = 0.763, P < .0001). Prognostic significance analysis indicated that lncRNA FRGCA had prognostic value in COAD [adjusted P < .001, hazard ratio (HR) = 0.444, 95% confidence interval (95% CI) = 0.288-0.685] and high expression of lncRNA FRGCA indicated better survival in COAD. A nomogram was evaluated for prediction of survival at 1, 3, and 5 years. Enrichment analysis revealed many mRNAs involved in the structural constituents of the mitochondrial inner membrane and translational termination, protein binding, translation, ribosome, oxidative phosphorylation, and metabolic pathways, especially the nucleoplasm.Differentially expressed in tumor vs nontumor tissues, lncRNA FRGCA had both diagnostic and prognostic implications in COAD, which may be associated with ribosome metabolism, oxidative phosphorylation, and nucleoplasm-related metabolic pathways.

Systematic and experimental investigations of the anti-colorectal cancer mediated by genistein.

Recent evidences have suggested that genistein, a beneficial isoflavonoid, exerts marked anti-proliferative action on colorectal cancer (CRC) cells. However, the exact molecular mechanisms behind anti-CRC effect of genistein have not been elucidated. In current report, a systemic pharmacology analysis was used to disclose the anti-CRC mechanism of genistein prior to performing experimentative certification. As shown in network pharmacology findings, a total of 189 common targets and 9 hard-core targets of genistein-anti-CRC were collected and identified. And the detailed anti-CRC functions and pathways mediated by genistein were uncovered. In further certification, human CRC samples resulted in elevated protein and mRNA expressions of myeloid leukemia cell differentiation protein (MCL1), beta amyloid A4 protein (APP), and vascular endothelial growth factor receptor 2 (KDR). In animal experiment, genistein-treated tumor-transplanted nude mice exhibited reduced tumor growth, accompanied with dose-dependent down-regulations of MCL1, APP, and KDR proteins and mRNAs. Taken together, the integrated bioinformatic and experimental findings uncover the anti-CRC mechanisms and targets mediated by genistein. Significantly, parts of hard-core biotargets were experimentally verified before clinical application, including MCL1, APP, and KDR.

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 value of L3 skeletal muscle index in evaluating preoperative nutritional risk and long-term prognosis in colorectal cancer patients.

L3 skeletal muscle index (L3SMI) was reportedly related to postoperative outcomes. We aimed to investigate the value of L3SMI in evaluating preoperative nutritional risk and long-term prognosis in colorectal cancer (CRC) patients. We retrospectively enrolled 400 CRC patients who underwent surgery from January 2012 to December 2014. The L3SMI was calculated by preoperative computed tomography (CT) and classified into two groups by gender quartile method. We found that the CT diagnostic criteria of sarcopenia in South China population was: male ≤38.89cm2/m2, female ≤33.28cm2/m2. Multivariate logistic regression analysis showed that low L3SMI was an independent risk factor for preoperative nutritional risk (p < 0.001). Kaplan-Meier survival curves showed that low status group had significantly lower disease-free survival (p = 0.004) and overall survival (p = 0.001), especially in TNM II stage. Multivariate Cox regression analysis revealed preoperative low L3SMI adversely affected disease-free survival (p < 0.001, HR 1.894 (95% CI: 1.330-2.698)), and overall survival (p < 0.001, HR 2.030 (95% CI: 1.420-2.902)). In conclusion, L3SMI is a useful supplement for screening preoperative nutritional risk and diagnosing sarcopenia, and a potential clinical indicator that can be used to predict the prognosis of CRC patients, especially TNM stage II patients.

The prognostic value of preoperative serum CA724 for CEA-normal colorectal cancer patients.

BACKGROUND AND PURPOSE: There had been no recognized serum tumor marker to predict the prognosis of colorectal cancer (CRC) patients with normal preoperative serum carcinoembryonic antigen (CEA) levels. The purpose of this study was to determine whether preoperative serum carbohydrate antigen 724 (CA724) was of predictive function for the prognosis of CRC patients with normal CEA levels. METHODS: The medical records of 295 CRC patients with normal CEA levels who underwent surgery at the Department of Colorectal Anal Surgery of the First Affiliated Hospital of Guangxi Medical University (Guangxi, China) between September 2012 and September 2014 were retrospectively reviewed. The Chi-square test was used to test the correlation between preoperative serum CA724 levels and clinical features. Kaplan-Meier curves were conducted to calculate the overall survival (OS) rate and disease-free survival (DFS) of patients. Cox regression analysis was applied to conduct univariate and multivariate analysis of the following four preoperative serum tumor makers namely CA724, carbohydrate antigen 199 (CA199), carcinoembryonic antigen 125 (CA125), carcinoembryonic antigen 242 (CA242) and clinical features. Nomograms for prognostic parameter of OS and DFS were developed using R v3.2.5. RESULTS: In the Chi-square test, only pathological node stage (pN stage) (X 2 = 14.514, P = 0.001) and differentiation (X 2 = 10.712, P = 0.001) were associated with serum CA724 levels. In the Kaplan-Meier analysis, the results revealed that the OS and DFS in patients with high CA724 was poorer than those with normal. In the multivariate Cox regression analysis of OS and DFS, only pT stage, pN stage, metastasis and serum CA724 were independent prognostic risk factors for CRC patients with normal CEA levels. CONCLUSION: Preoperative serum CA724 might serve as a potential prognostic factor for CRC patients with normal serum CEA levels.

Computed Tomography-Determined Sarcopenia Is a Useful Imaging Biomarker for Predicting Postoperative Outcomes in Elderly Colorectal Cancer Patients.

PURPOSE: This study aimed to establish whether computed tomography (CT)-determined sarcopenia is a useful imaging biomarker for postoperative outcome in elderly colorectal cancer (CRC) patients, and construct sarcopenia-based nomograms to predict individual outcomes after surgery. MATERIALS AND METHODS: CT imaging data of 298 elderly CRC patients who underwent surgery in 2012-2014 were retrospectively analyzed. Skeletal muscle mass was determined by CT, and sarcopenia was diagnosed based on the optimal cutoff value determined by X-tile program. The correlation between sarcopenia and risk of preoperative nutrition and postoperative complications was evaluated. A Cox proportional hazards model was used to determine survival predictors. Sarcopenia-based nomograms were developed based on multivariate analysis, and calibrated using concordance index and calibration curves. RESULTS: A total 132 patients (44.3%) had sarcopenia based on the optimum cutoff values (29.9 cm2/m2 for women and 49.5 cm2/m2 for men). Sarcopenia was an independent risk factor for preoperative nutrition (p < 0.001; odds ratio [OR], 3.405; 95% confidence interval [CI], 1.948 to 5.954) and postoperative complications (p=0.008; OR, 2.192; 95% CI, 1.231 to 3.903). Sarcopenia was an independent predictor for poor progression-free survival (p < 0.001; hazard ratio [HR], 2.175; 95% CI, 1.489 to 3.179) and overall survival (p < 0.001; HR, 2.524; 95% CI, 1.721 to 3.703). Based on multivariate analysis, we produced four nomograms that had better predictive performance. CONCLUSION: CT-determined sarcopenia is a useful imaging biomarker for predicting preoperative nutritional risk, postoperative complications, and long-term outcomes in elderly CRC patients. The sarcopenia-based nomograms can provide a scientific basis for guiding therapeutic schedule and follow-up strategies.