Good Prognostic Value Research Articles

Collagen score in the tumor microenvironment predicts the prognosis of rectal cancer patients after neoadjuvant chemoradiotherapy

Background and purposeLittle is known about the relationship between collagen and the prognosis of patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). This study aimed to quantitatively analyze collagen alterations, establish a collagen score (CS) in the tumor microenvironment, and evaluate and validate the relationship of the CS with prognosis in these patients. Materials and methodsA total of 365 primary patients diagnosed with LARC after nCRT between 2011 and 2018 were retrospectively reviewed (training cohort: 210; independent validation cohort: 155). Multiple collagen features of two fields in the tumor microenvironment, the core of the tumor (CT) and the invasive margin (IM), were derived from multiphoton imaging, and the CSIM-CT was generated using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. ResultsThe CSIM-CT was created based on 3 features: collagen area, number of collagen fibers and a Gabor textural feature. In the training cohort, the CSIM-CT predicted 3-year disease-free survival (DFS) with an area under the receiver operating characteristic curve (AUROC) of 0.765 (0.675–0.854) and an overall survival (OS) with AUROC of 0.822 (0.734–0.909). Additionally, the CSIM-CT was significantly associated with DFS and OS in the two cohorts. A nomogram with the CSIM-CT was developed and showed good prognostic value predicting a 3-year DFS with an AUROC of 0.826 (0.748–0.905) and an OS with AUROC of 0.882 (0.803–0.960). ConclusionsThe CSIM-CT is an effective prognostic marker in patients with LARC after nCRT, and the nomogram with the CSIM-CT can be used to accurately predict the individual prognosis of these patients.

JAM2 predicts a good prognosis and inhibits invasion and migration by suppressing EMT pathway in breast cancer

ObjectivesLarge-scale epidemiological surveys have shown that patients with Down syndrome, which is caused by a chromosomal abnormality (an extra chromosome 21), are significantly less likely to develop solid tumors, including breast cancer, than those without. This feature has prompted the search for oncogenes located on chromosome 21. Junctional adhesion molecule 2 (JAM2), which is located on chromosome 21, is expressed at low levels in breast cancer and is associated with a good prognosis. These findings strongly suggest that JAM2 may be a potential oncogene suppressor in breast cancer. However, the role and function of JAM2 in breast cancer are not yet clear. Therefore, this study aimed to explore the biological functions and mechanisms of JAM2 in breast cancer. MethodsSeveral databases were used to explore JAM2 expression in breast cancer and to analyze its diagnostic and prognostic value in breast cancer. Changes in relevant markers were examined at the gene and protein levels using RT-qPCR and Western blot techniques, in addition, cell migration and invasion abilities were identified by scratch assays and transwell assays. Untargeted metabolomics, transcriptome sequencing and Luminex liquid suspension chip detection were performed in combination to study the mechanisms. ResultsJAM2 is expressed at low levels in breast cancer, and patients with high JAM2 expression have a good prognosis, indicating that JAM2 has good clinical diagnostic and prognostic value. Overexpression of JAM2 can block the invasion and migration of breast cancer cells, and the mechanism may be that JAM2 inhibits the EMT pathway. Finally, combined multiomics analysis revealed that JAM2 may affect the immune microenvironment of breast cancer by influencing the secretion of CXCL9/10 from tumor cells.

Prognostic Value of Late Enhanced Cardiac Magnetic Resonance Imaging Derived Texture Features in Dilated Cardiomyopathy Patients With Severely Reduced Ejection Fractions.

Background: Late enhanced cardiac magnetic resonance (CMR) images of the left ventricular myocardium contain an enormous amount of information that could provide prognostic value beyond that of late gadolinium enhancements (LGEs). With computational postprocessing and analysis, the heterogeneities and variations of myocardial signal intensities can be interpreted and measured as texture features. This study aimed to evaluate the value of texture features extracted from late enhanced CMR images of the myocardium to predict adverse outcomes in patients with dilated cardiomyopathy (DCM) and severe systolic dysfunction.Methods: This single-center study retrospectively enrolled patients with DCM with severely reduced left ventricular ejection fractions (LVEFs < 35%). Texture features were extracted from enhanced late scanning images, and the presence and extent of LGEs were also measured. Patients were followed-up for clinical endpoints composed of all-cause deaths and cardiac transplantation. Cox proportional hazard regression and Kaplan–Meier analyses were used to evaluate the prognostic value of texture features and conventional CMR parameters with event-free survival.Results: A total of 114 patients (37 women, median age 47.5 years old) with severely impaired systolic function (median LVEF, 14.0%) were followed-up for a median of 504.5 days. Twenty-nine patients experienced endpoint events, 12 died, and 17 underwent cardiac transplantations. Three texture features from a gray-level co-occurrence matrix (GLCM) (GLCM_contrast, GLCM_difference average, and GLCM_difference entropy) showed good prognostic value for adverse events when analyzed using univariable Cox hazard ratio regression (p = 0.007, p = 0.011, and p = 0.007, retrospectively). When each of the three features was analyzed using a multivariable Cox regression model that included the clinical parameter (systolic blood pressure) and LGE extent, they were found to be independently associated with adverse outcomes.Conclusion: Texture features related LGE heterogeneities and variations (GLCM_contrast, GLCM_difference average, and GLCM_difference entropy) are novel markers for risk stratification toward adverse events in DCM patients with severe systolic dysfunction.

Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China.

ObjectiveAntithyroglobulin antibody (TgAb) is a potential tumour marker for detecting differentiated thyroid cancer (DTC) recurrence, but insufficient data have supported its clinical applications. Our study aimed to describe the changing trend of TgAb after surgery and identify the relationship between this trend and clinical outcomes.Patients and MethodsWe reviewed the electronic records of 1,686 DTC patients who had undergone total thyroidectomy (TT) and radioactive iodine (131I) therapy at West China Hospital of Sichuan University from January 2015 to December 2017. Finally, 289 preoperative TgAb-positive DTC patients were included and divided into four subgroups depending on the clinical outcome: Group A (tumour free), Group B (uncertain), Group C (incomplete biochemical response), and Group D (structural disease). The patient demographics, tumour characteristics, operations, pathology reports, and all serological biomarkers were reviewed and compared, and the prognostic efficacy of TgAb was evaluated.ResultsAmong all 1,686 patients, 393 (23.65%) were TgAb positive (>40 IU/ml) preoperatively. The TgAb level in Group A decreased significantly after surgery and 131I therapy and stabilised at a low level after 1–2 years of 131I therapy. However, in the other three groups, the decrease in TgAb was not significant after treatment. Conversely, TgAb declined slowly and remained stable or increased. The variations in TgAb relative to the preoperative level of Group A were significantly larger than those of Groups B, C, and D at most time points of follow-up (p < 0.001). By receiver operating characteristic (ROC) analyses, the variations of TgAb > −77.9% at 6 months after 131I therapy (area under the curve (AUC) = 0.862; p < 0.001) and TgAb > −88.6% at 2 years after 131I therapy (AUC = 0.901; p < 0.001) had good prognostic efficacy in tumour-free survival. When the variation in TgAb > −88.6% at 2 years after 131I therapy was incorporated as a variable in the American Thyroid Association (ATA) categories, both intermediate- and high-risk patients also had a significantly increased chance of being tumour free (from 75.68% to 93.88% and 42.0% to 82.61%, respectively).ConclusionsFor preoperative TgAb-positive DTC patients, variations in TgAb > −77.9% at 6 months after 131I therapy and TgAb > −88.6% at 2 years after 131I therapy had good prognostic efficacy. Their incorporation as variables in the ATA risk stratification system could more accurately predict disease-free survival.

Immune Score-based Molecular Subtypes and Signature Associated with Clinical Outcome in Hepatoblastoma

Background: This study aimed to identify genes related to the immune score of hepatoblastoma, examine the characteristics of the immune microenvironment of hepatoblastoma, and construct a risk scoring system for predicting the prognosis of hepatoblastoma. Methods: Through using the gene chip data of patients with hepatoblastoma with survival data in the ArrayExpress and GEO databases, the immune score of hepatoblastoma was calculated by the ESITIMATE algorithm, and the prognostic value of immune score in patients with hepatoblastoma was studied by the survival analysis. Genes related to the immune score were identified by the WGCNA algorithm. According to these genes, patients with hepatoblastoma were clustered unsupervised. Finally, the risk scoring system was constructed according to the immune score-related genes. Results: The immune score calculated by the ESTIMATE algorithm had a good prognostic value in patients with hepatoblastoma. Patients with high immune scores had better OS than those with low immune scores (P &lt; 0.001). A total of 146 immune score-related genes were identified by WGCNA analysis, and univariate COX regression analysis indicated that 59 of the genes had prognostic value. According to the unsupervised clustering results of the 146 immune score-related genes, patients with hepatoblastoma could be divided into two subtypes with different prognoses, namely molecular subtype 1 and subtype 2, with molecular subtype 1 having a better prognosis. The immunocyte infiltration analysis results showed that the difference between the two subtypes was mainly in activated CD4 T cells, activated dendritic cells, CD56 bright natural killer cells, the macrophage, and regulatory T cells. According to the immune score-related genes, a risk scoring system was constructed based on a five-gene signature. After the cut-off value was determined, patients with hepatoblastoma were divided into a high-risk group and a low-risk group. The prognosis of the two groups was different. Conclusions: The immune score has a good prognostic value in patients with hepatoblastoma. Based on the different expression patterns of immune score-related genes, hepatoblastoma can be divided into two different prognostic molecular subtypes, showing different immunocyte infiltration patterns. The established risk scoring system based on a five-gene signature has a good predictive value in patients with hepatoblastoma.

A prognostic nomogram based on a new classification of combined micropapillary and solid components for stage IA invasive lung adenocarcinoma.

We aimed to develop a prognostic nomogram based on a new classification of combined micropapillary and solid components in pathological stage IA invasive lung adenocarcinoma (LUAD). According to the total proportion of solid and micropapillary components (TPSM), the X-tile software was applied to classify patients into the following three groups: TPSM-low (TPSM-L), TPSM-middle (TPSM-M), and TPSM-high (TPSM-H). The postoperative survival was compared among the three groups. The multivariate Cox regression analysis was performed to identify independent prognostic factors for survival. According to these factors, a nomogram model was developed to provide a personalized prognostic evaluation. A total of 595 patients with pathological stage IA invasive LUAD were included in our study. The 5-year disease-free survival and overall survival rates in patients with TPSM-H and TPSM-M were significantly lower than those with TPSM-L. The multivariate Cox regression analysis revealed that the TPSM classification was an independent prognostic factor for survival. According to TPSM classification, we developed a nomogram model which had good calibration and reliable discrimination ability to evaluate survival. The nomogram based on the combination of micropapillary and solid components has good prognostic value in predicting postoperative recurrence and survival of patients with pathological stage IA invasive LUAD.

Low serum prealbumin concentration predicts long-term mortality in maintenance hemodialysis patients with hepatitis B and/or C virus infections.

Background and AimA low serum prealbumin concentration is common in maintenance hemodialysis patients with hepatitis B and C and may be associated with mortality. In this study, we assessed Department of Nephrology and Hemodialysis predictive value of a low serum prealbumin concentration on mortality in HD patients using reused low‐flux dialyzers who were infected with hepatitis B and/or C virus.MethodsWe used serum prealbumin levels to predict the long‐term mortality of 326 hemodialysis patients. The patients were divided into two groups: group 1 (n = 140, with hepatitis B and/or C virus infections), and group 2 (n = 186, without hepatitis virus infections).ResultsDuring a 5‐year follow‐up, there were 75 deaths due to all‐cause mortality (23.0%). Mortality was significantly higher (P < 0.001) in patients with hepatitis B and/or C infection (44%) than in those without hepatitis infection (8%). Serum prealbumin was lower in the hepatitis infected group and mortality group than in non‐infected group and survival group. Multivariate Cox regression analysis showed that long duration of HD and lower serum prealbumin and albumin were related to mortality in patients undergoing maintenance HD. Receiver operating characteristic curves showed that serum prealbumin had a good prognostic value in predicting mortality in both groups with hepatitis B and/or C virus infection and without hepatitis infection (AUC = 0.792 [95% confidence interval: 0.714–0.87], P < 0.001; cut‐off value = 24.5 mg/dl, sensitivity = 62.3%, and specificity = 88.6%).ConclusionIn HD patients, serum prealbumin was a good prognostic biomarker of mortality in both groups of patients with hepatitis B and/or C virus infections and without hepatitis infections.

Conjoint analysis of circulating tumor cells and solid tumors for exploring potential prognostic markers and constructing a robust novel predictive signature for breast cancer

BackgroundDistance metastasis is the leading cause of death for breast cancer patients, and circulating tumor cells (CTCs) play a key role in cancer metastasis. There have been few studies on CTCs at the molecular level due to their rarity, and the heterogeneity of CTCs may provide special information for solid tumor analysis.MethodsIn this study, we used the gene expression and clinical information of single-cell RNA-seq data of CTCs of breast cancer and discovered a cluster of epithelial cells that had more aggressive characteristics. The differentially expressed genes (DEGs) between the identified epithelial cells cluster and others from single-CTCs were selected for further analysis in bulk sequence data of solid breast cancers.ResultsEighteen genes closely related to the specific CTC epithelial phenotype and breast cancer patient prognosis were identified. Among these 18 genes, we selected the GARS gene, which has not been studied in breast cancer, for functional research and confirmed that it may be a potential oncogene in breast cancer. A risk score was established by the 18 genes, and a high-risk score was strongly associated with a high metastasis rate and poor survival prognosis in breast cancer. The high-risk score group was related to a defective immune infiltration environment in breast cancer, and the immune checkpoint therapy response rate was lower in this group. The drug-sensitive analysis shows that the high-risk score patients may be more sensitive to AKT-mTOR and the cyclin-dependent kinase (CDK) pathways drugs than low-risk score patients.ConclusionsOur 18-gene risk score shows good prognostic and predictive values and might be a personalized prognostic marker or therapy guide marker in breast cancer patients.

Novel Diffusion-Weighted Imaging Score Showed Good Prognostic Value for Acute Basilar Artery Occlusion Following Endovascular Treatment: The Pons-Midbrain and Thalamus Score.

Prognostic factors for outcome of endovascular treatment remains to be investigated in patients with acute basilar artery occlusion. We aimed to assess the prognostic value of a novel pretreatment diffusion-weighted imaging score: The Pons-Midbrain and Thalamus (PMT) score. Eligible patients who underwent endovascular treatment due to acute basilar artery occlusion were reviewed. The PMT score was a diffusion-weighted imaging-based semiquantitative scale in which the infarctions of pons, midbrain, and thalamus were fully considered. The PMT score was assessed as well as the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score and Brain Stem Score. Good outcomes were defined as a modified Rankin Scale score of ≤3 at 90-day and successful reperfusion as Thrombolysis in Cerebral Infarction grades 2b/3. The associations between baseline clinical parameters and good outcomes were evaluated with logistic regression. A total of 107 patients with pretreatment magnetic resonance imaging were included in this cohort. The baseline PMT score (median [interquartile range], 3 [1-5] versus 7 [5-9]; P<0.001) and Brain Stem Score (median [interquartile range], 2 [1-4] versus 3 [2-5]; P=0.001) were significantly lower in good outcome group; the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score was higher in good outcome group without statistical significance. As a result of receiver operating characteristic curve analyses, the posterior circulation Acute Stroke Prognosis Early Computed Tomography Score showed poor prognostic accuracy for good outcome (area under the curve, 0.60 [95% CI, 0.49-0.71]; P=0.081); The baseline PMT score showed significantly better prognostic accuracy for 90-day good outcome than the Brain Stem Score and National Institutes of Health Stroke Scale (area under the curve, 0.80 versus 0.68 versus 0.78, P=0.003). In addition, favorable PMT score <7 (odds ratio, 22.0 [95% CI, 6.0-80.8], P<0.001), Brain Stem Score <3 (odds ratio, 4.65 [95% CI, 2.05-10.55], P<0.001) and baseline National Institutes of Health Stroke Scale <23 (odds ratio, 8.0 [95% CI, 2.5-25.6], P<0.001) were associated with improved good outcome. In patients with acute basilar artery occlusion following endovascular treatment, the pretreatment diffusion-weighted imaging based PMT score showed good prognostic value for clinical outcome.

Integrative Analysis of Prognostic Value and Immune Infiltration of Spindle and Kinetochore-associated Family Members in Breast Cancer

ABSTRACT Spindle and kinetochore associated (SKA) complex subunit, which maintains the stability of mitotic metaphase, with emerging research implying its effect as a carcinogenic regulator in cancer. However, its potential role in BC has not been fully elucidated. ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, cBioPortal and TIMER databases were performed to analyze the expression, prognosis, mutation, immune infiltration and potential biological mechanisms of SKA1/2/3 in BC. Our results showed that SKA1/2/3 expression was upregulated in BC. Survival analysis reveals that SKA3 overexpression was associated with poor overall survival (OS), relapse-free survival (RFS), post-progression survival (PPS) and distant metastasis-free survival (DMFS). SKA1 overexpression was associated with poor OS, RFS and DMFS while SKA2 overexpression was only associated with RFS and DMFS. Notably, the results implied that SKA1 has a good prognostic value in HER2-positive BC. Besides, the genetic alterations of SKA were investigated and the altered group correlated with shorter progress-free survival (PFS) and disease-specific survival (DSS). GO and KEGG analysis showed that SKA1/2/3 were implicated in regulating cell cycle, p53 signaling pathway and DNA replication. The 10 Hub genes in the protein network were upregulated in BC and related to poorer prognosis. Additionally, SKA1/2/3 expression was negatively correlated with infiltration of various immune cells with antitumor effects, whereas positively correlated with the expression of immune checkpoints molecules. Further experiments revealed that SKA1/2/3 silencing markedly impeded the proliferation and migration of BC cells. Herein, our study firmly shows that SKA genes may serve as a promising therapeutic target for patients with BC.

Identification and Validation of an 6-Metabolism-Related Gene Signature and Its Correlation With Immune Checkpoint in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor with relatively high malignancy and rapid disease progression. Metabolism-related genes (MRGs) are involved in the pathogenesis of HCC. This study explored potential key MRGs and their effect on T-cell immune function in the tumor immune microenvironment to provide new insight for the treatment of HCC. Of 456 differentially expressed MRGs identified from TCGA database, 21 were screened by MCODE and cytoHubba algorithms. From the key module, GAD1, SPP1, WFS1, GOT2, EHHADH, and APOA1 were selected for validation. The six MRGs were closely correlated with survival outcomes and clinicopathological characteristics in HCC. Receiver operating characteristics analysis and Kaplan-Meier plots showed that these genes had good prognostic value for HCC. Gene set enrichment analysis of the six MRGs indicated that they were associated with HCC development. TIMER and GEPIA databases revealed that WFS1 was significantly positively correlated and EHHADH was negatively correlated with tumor immune cell infiltration and immune checkpoint expression. Finally, quantificational real-time polymerase chain reaction (qRT-PCR) confirmed the expression of WFS1 and EHHADH mRNA in our own patients’ cohort samples and four HCC cell lines. Collectively, the present study identified six potential MRG biomarkers associated with the prognosis and tumor immune infiltration of HCC, thus providing new insight into the pathogenesis and treatment of HCC.

RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway.

BackgroundGlioblastoma (GBM) is a prevalent brain malignancy with an extremely poor prognosis, which is attributable to its invasive biological behavior. The RNA-binding motif protein 8A (RBM8A) has different effects on various human cancers. However, the role of RBM8A in GBM progression remains unclear.MethodsWe investigated the expression levels of RBM8A in 94 GBM patients and explored the correlation between RBM8A expression and patient prognosis. Using in vitro and in vivo assays, combined with GBM sequencing data from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we examined whether and how RBM8A contributes to GBM progression.ResultsRBM8A was up-regulated in GBM tissues, and its higher expression correlated with worse prognosis. Knockdown of RBM8A inhibited GBM progression and invasion ability both in vitro and in vivo. On the contrary, overexpression of RBM8A promoted GBM progression and invasion ability. Enrichment analysis of differentially expressed genes in GBM data identified the Notch1/STAT3 network as a potential downstream target of RBM8A, and this was supported by molecular docking studies. Furthermore, we demonstrated that RBM8A regulates the transcriptional activity of CBF1. The γ-secretase inhibitor DAPT significantly reversed RBM8A-enhanced GBM cell proliferation and invasion, and was associated with down-regulation of p-STAT3 and Notch1 protein. Finally, the gene set variance analysis score of genes involved in regulation of the Notch1/STAT3 network by RBM8A showed good diagnostic and prognostic value for GBM.ConclusionsRBM8A may promote GBM cell proliferation and migration by activating the Notch/STAT3 pathway in GBM cells, suggesting that RBM8A may serve as a potential therapeutic target for the treatment of GBM.

The prognostic value of the lymph node ratio in patients with stage IIIC ovarian cancer treated with preoperative chemotherapy.

Ovarian cancer is a major cause of morbidity and mortality in females. Due to the unremarkable symptoms associated with early ovarian cancer, many patients are already in the advanced stages at first diagnosis. Recent studies have shown that the lymph node ratio (LNR) has a certain value in predicting the prognosis of patients with ovarian cancer. However, preoperative chemotherapy may lead to changes in the LNR, and thus, the predictive value of the LNR in such patients is unclear. Therefore, this study examined the predictive value of the LNR in ovarian cancer patients undergoing preoperative chemotherapy. A total of 208 patients with stage IIIC ovarian cancer, who were treated in the Fourth Clinical Medical College of Xinxiang Medical University, Xinxiang Central Hospital from January 2014 to January 2016, were recruited for this study. The median LNR was 0.32. Patients with LNR <0.32 were defined as the control group and those with LNR ≥0.32 were defined as the observation group. The prognosis of the two groups was compared. The LNR in the observation group was significantly higher than that of the control group (0.63±0.21 vs. 0.19±0.08; P=0.000). Patients in the observation group showed significantly higher postoperative recurrence rates (51.92% vs. 22.12%; P=0.000), greater incidences of postoperative metastasis (43.27% vs. 17.31%; P=0.000), and significantly increased postoperative mortality (36.54% vs. 11.54%; P=0.000) compared to the control group. The survival function showed that the overall survival, recurrence-free survival, and metastasis-free survival were all significantly shorter in the observation group compared to the control group (P=0.000). The receiver operating characteristic curves showed that the LNR had certain diagnostic value for postoperative recurrence [area under the curve (AUC) =0.658; 95% confidence interval (CI): 0.582 to 0.734; P=0.000], postoperative metastasis (AUC =0.640; 95% CI: 0.560 to 0.720; P=0.001), and postoperative mortality (AUC =0.653; 95% CI: 0.569 to 0.737; P=0.001) in patients with stage IIIC ovarian cancer treated with preoperative chemotherapy. The LNR has good prognostic value in patients with locally advanced ovarian cancer treated with preoperative chemotherapy.

Development and Validation of an Immune-Related Gene Pairs Signature in Grade II/III Glioma.

BackgroundGliomas are prevalent primary intracerebral malignant tumors. Increasing evidence indicates an association between the immune signature and Grade II/III glioma prognosis. Thus, we aimed to develop an immune-related gene pair (IRGP) signature that can be used as a prognostic tool in Grade II/III glioma.MethodsThe gene expression levels and clinical information of Grade II/III glioma patients were collected from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. The TCGA data were randomly divided into a training cohort (n = 249) and a validation cohort (n = 162), and a CGGA dataset served as an external validation group (n = 605). IRGPs significantly associated with prognosis were selected by Cox regression. Gene set enrichment analysis and filtration were performed with the IRGPs.ResultsWithin a set of 1991 immune genes, 8 IRGPs including 15 unique genes that significantly affect survival constituted a gene signature. In the validation datasets, the IRGP signature significantly stratified patients with Grade II/III glioma into low- and high-risk groups (P < 0.001), and the IRGP index was found to be an independent prognostic factor through univariate and multivariate analyses (P < 0.05). Additionally, 26 functional pathways were identified through the intersection of Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) enrichment analysis.ConclusionThe IRGP signature demonstrated good prognostic value for Grade II/III gliomas, which may provide new insights into individual treatment for glioma patients. The IRGPs might function through the identified 26 functional pathways.

Prognostic Impact of Cytotoxic CD4 T Cells in Tumor Immune Microenvironment of Patients with Breast Cancer.

Prognostic Impact of Cytotoxic CD4 T Cells in Tumor Immune Microenvironment of Patients with Breast Cancer.

Predictive value and regulatory mechanism of serum miR-499a-5p on myocardial dysfunction in sepsis

BackgroundThis study sought to investigate the predictive value and regulatory mechanism of serum miR-499a-5p in sepsis-induced myocardial dysfunction (SIMD).MethodsA total of 60 patients with sepsis and 60 healthy volunteers were enrolled in this study. The serum levels of miRNAs (miR-451, miR-378 and miR-499a-5p) were detected. Receiver operating characteristic curve and logistic regression analysis were used to evaluate the diagnostic and prognostic value of miR-499a-5p in SIMD patients. AC16 cells were used to establish SIMD model in vitro using lipopolysaccharide (LPS). An analysis was conducted for miR-499a-5p expression, cell viability, and the concentration of creatine kinase-MB isoform (CK-MB), brain natriuretic peptide (BNP), superoxide dismutase (SOD) and cytochrome C oxidase IV (COX IV). The downstream target of miR-499a-5p was verified.ResultsOur results revealed a poor expression of miR-499a-5p in the serum of SIMD patients, while no significant difference was evident for miR-451 and miR-378. The level of miR-499a-5p in the survival group was higher than the non-survival group. miR-499a-5p elicited good diagnostic and prognostic value for SIMD. Our findings revealed that miR-499a-5p was decreased significantly in LPS-treated cardiomyocytes. After overexpression of miR-499a-5p, the cell viability increased, and the concentrations of CK-MB and BNP were decreased, while the concentrations of SOD and COX IV were increased. EIF4E was validated as the target of miR-499a-5p. After overexpression of EIF4E, the cell viability was decreased and the concentrations of CK-MB and BNP were increased while the concentrations of SOD and COX IV were decreased.ConclusionThe level of miR-499a-5p is weak in SIMD patients. miR-499a-5p has a good diagnostic and prognostic value for SIMD by inhibiting EIF4E transcription.

Exploration of a Novel Prognostic Risk Signature and Its Effect on the Immune Response in Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic carcinoma with different molecular characteristics and clinical outcomes. In this work, we aimed to establish a novel gene signature that could predict the prognosis of NPC patients. A total of 13 significant genes between the recurrence/metastasis (RM) group and the no recurrence/metastasis (no-RM) group were identified by machine learning from RNA-Seq data including 60 NPC tumor biopsies. Based on these genes, a 4-mRNA signature (considering U2AF1L5, TMEM265, GLB1L and MLF1) was identified. Receiver operating characteristic (ROC) and Kaplan-Meier (K-M) analyses indicated that this signature had good prognostic value for NPC. The overall survival (OS) and progression-free survival (PFS) of the patients in the high-risk group were significantly shorter than those of the patients in the low-risk group (p = 0.00126 and p = 0.000059, respectively). The area under the ROC curve (AUC) values of the 4-mRNA signature were higher than those of T stage and N stage for OS (0.893 vs 0.619 and 0.582, respectively) and PFS (0.86 vs 0.538 and 0.622, respectively). Furthermore, the 4-mRNA signature was closely associated with cell proliferation and the immune response. The expression of GLB1L and TMEM265 was associated with the level of tumor-infiltrating immune cells (r > 0.4, p < 0.05). We have validated the model through measuring the expression levels of the 4-mRNA signature by qRT-PCR, in an independent cohort of NPC patients. Here, we report a novel gene signature that can serve as a new tool for predicting the prognosis of NPC patients.

Integrative Analysis of Metallothioneins Identifies MT1H as Candidate Prognostic Biomarker in Hepatocellular Carcinoma.

Background: Metallothioneins (MTs) play crucial roles in the modulation of zinc/copper homeostasis, regulation of neoplastic growth and proliferation, and protection against apoptosis. The present study attempted to visualize the prognostic landscape of MT functional isoforms and identify potential prognostic biomarkers in hepatocellular carcinoma (HCC). Methods: The transcriptional expression, comprehensive prognostic performances, and gene–gene interaction network of MT isoforms in HCC were evaluated via Oncomine, GEPIA, Kaplan–Meier plotter, and GeneMANIA databases. Characterized by good prognostic value in three external cohorts, MT1H was specifically selected as a potential prognostic biomarker in HCC with various clinicopathological features. Functional and pathway enrichment analyses of MT1H status were performed using cBioPortal, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), and ssGSVA method. Results: MT1E/1F/1G/1H/1M/1X/2A was greatly downregulated in HCC. Prognostic analyses elucidated the essential correlations between MT1A/1B/1H/1X/2A/4 attenuation and poor overall survival, between MT1B/1H/4 downregulation and worse relapse-free survival, and between MT1A/1B/1E/1H/1M/2A/4 downregulation and diminished progression-free survival in HCC. Taken together, these results indicated the powerful prognostic value of MT1H among MTs in HCC. In-depth analyses suggested that MT1H may be more applicable to alcohol-derived HCC and involved in the downregulation of the inflammatory pathway, Jak–STAT pathway, TNF pathway, and Wnt signaling pathway. Conclusion: MT-specific isoforms displayed aberrant expression and varying prognostic value in HCC. MT1H repression in HCC was multi-dimensionally detrimental to patient outcomes. Therefore, MT1H was possibly associated with carcinogenesis and exploited as a novel prognostic biomarker and candidate therapeutic target for HCC.

Assessment of Clinicopathological Characteristics and Development of an Individualized Prognostic Model for Patients With Hepatoid Adenocarcinoma of the Stomach

Few studies have examined the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma of the stomach (HAS). To explore the clinicopathological characteristics and prognoses of patients with HAS and develop a nomogram to predict overall survival (OS). This prognostic study involved a retrospective analysis of data from 315 patients who received a diagnosis of primary HAS between April 1, 2004, and December 31, 2019, at 14 centers in China. OS and prognostic factors. Patients were randomly assigned to a derivation cohort (n = 220) and a validation cohort (n = 95). A nomogram was developed based on independent prognostic factors identified through a multivariable Cox mixed-effects model. Among 315 patients with HAS (mean [SD] age, 61.9 [10.2] years; 240 men [76.2%]), 137 patients had simple HAS (defined as the presence of histologically contained hepatoid differentiation areas only), and 178 patients had mixed HAS (defined as the presence of hepatoid differentiation areas plus common adenocarcinoma areas). Patients with simple HAS had a higher median preoperative α-fetoprotein level than those with mixed HAS (195.9 ng/mL vs 48.9 ng/mL, respectively; P < .001) and a higher rate of preoperative liver metastasis (23 of 137 patients [16.8%] vs 11 of 178 patients [6.2%]; P = .003). The 3-year OS rates of patients with simple vs mixed HAS were comparable (56.0% vs 60.0%; log-rank P = .98). A multivariable Cox analysis of the derivation cohort found that the presence of perineural invasion (hazard ratio [HR], 2.13; 95% CI, 1.27-3.55; P = .009), preoperative carcinoembryonic antigen levels of 5 ng/mL or greater (HR, 1.72; 95% CI, 1.08-2.74; P = .03), and pathological node category 3b (HR, 3.72; 95% CI, 1.34-10.32; P = .01) were independent risk factors for worse OS. Based on these factors, a nomogram to predict postoperative OS was developed. The concordance indices of the nomogram (derivation cohort: 0.72 [95% CI, 0.66-0.78]; validation cohort: 0.72 [95% CI, 0.63-0.81]; whole cohort: 0.71 [95% CI, 0.66-0.76]) were higher than those derived using the American Joint Committee on Cancer's AJCC Cancer Staging Manual (8th edition) pathological tumor-node-metastasis (pTNM) staging system (derivation cohort: 0.63 [95% CI, 0.57-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]) and those derived using a clinical model that included pTNM stage and receipt of adjuvant chemotherapy (derivation cohort: 0.64 [95% CI, 0.58-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]). Based on the nomogram cutoff of 10 points, the whole cohort was divided into high-risk and low-risk groups. The 3-year OS rate of patients in the high-risk group was significantly lower than that of patients in the low-risk group (29.7% vs 75.9%, respectively; log-rank P < .001), and the 3-year prognosis of high-risk and low-risk groups could be further distinguished into pTNM stage I to II (33.3% vs 80.2%; exact log-rank P = .15), stage III (34.3% vs 71.3%; log-rank P < .001), and stage IV (15.5% vs 70.3%; log-rank P = .009). This study found that perineural invasion, preoperative carcinoembryonic antigen levels of 5 ng/mL or greater, and pathological node category 3b were independent risk factors associated with worse OS. An individualized nomogram was developed to predict OS among patients with HAS. This nomogram had good prognostic value and may be useful as a supplement to the current American Joint Committee on Cancer TNM staging system.

Applying immune-related lncRNA pairs to construct a prognostic signature and predict the immune landscape of stomach adenocarcinoma

ABSTRACT Background: Long noncoding RNAs (lncRNAs) are associated with the survival of cancer patients. We constructed an immune-related lncRNA (irlncRNA) pair signature for stomach adenocarcinoma (STAD). Research design and methods: irlncRNAs were identified via coexpression analysis with immune-related genes. Differentially expressed irlncRNAs (DEirlncRNAs) were paired. Least absolute shrinkage and selection operator (LASSO) and multivariate Cox proportional hazards regression methods were used to construct the signature. We calculated the area under the receiver operating characteristic (ROC) curve and determined the best cutoff value according to the Akaike information criterion (AIC). Patients were divided into high – and low-risk groups, and differences in immune cell infiltration, tumor mutation burden (TMB) and drug treatment effects between the groups were explored according to the risk score. Results: An 8-irlncRNA-pair signature was constructed and proven to be a strong prognosis predictor in STAD patients through external verification. Moreover, the risk score was identified as an independent prognostic factor. There were significant differences in immune cell infiltration and the response to several drug treatments between patients with high and low risk scores, and the risk score was negatively correlated with TMB. Conclusions: The signature consisting of 8 irlncRNA pairs showed good prognostic predictive value.