Independent Predictor For Patients Research Articles

Identification of a Liver Progenitor Cell-Related Genes Signature Predicting Overall Survival for Hepatocellular Carcinoma.

Background: Liver progenitor cells (LPCs) play significant roles in the development and progression of hepatocellular carcinoma (HCC). However, no studies on the value of LPC-related genes for evaluating HCC prognosis exist. We developed a gene signature of LPC-related genes for prognostication in HCC. Methods: To identify LPC-related genes, we analyzed mRNA expression arrays from a dataset (GSE57812 & GSE 37071) containing LPCs, mature hepatocytes, and embryonic stem cell samples. HCC RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to explore the differentially expressed genes (DEGs) related to prognosis through DEG analysis and univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed to construct the LPC-related gene prognostic model in the TCGA training dataset. This model was validated in the TCGA testing set and an external dataset (International Cancer Genome Consortium [ICGC] dataset). Finally, we investigated the relationship between this prognostic model with tumor-node-metastasis stage, tumor grade, and vascular invasion of HCC. Results: Overall, 1770 genes were identified as LPC-related genes, of which 92 genes were identified as DEGs in HCC tissues compared with normal tissues. Furthermore, we randomly assigned patients from the TCGA dataset to the training and testing cohorts. Twenty-six DEGs correlated with overall survival (OS) in the univariate Cox regression analysis. Lasso and multivariate Cox regression analyses were performed in the TCGA training set, and a 3-gene signature was constructed to stratify patients into 2 risk groups: high-risk and low-risk. Patients in the high-risk group had significantly lower OS than those in the low-risk group. Receiver operating characteristic curve analysis confirmed the signature's predictive capacity. Moreover, the risk score was confirmed to be an independent predictor for patients with HCC. Conclusion: We demonstrated that the LPC-related gene signature can be used for prognostication in HCC. Thus, targeting LPCs may serve as a therapeutic alternative for HCC.

Prognostic value of peripheral blood T lymphocyte subsets in clear cell renal cell carcinoma.

BackgroundTo date, few studies have evaluated the role of peripheral blood T lymphocyte subsets in patients with clear cell renal cell carcinoma (ccRCC). Here we measured the levels of peripheral blood T lymphocyte subsets and evaluated its prognostic value in ccRCC.MethodsData from 122 patients with RCC from January 2018 to January 2020 were collected. Preoperative peripheral blood T lymphocyte subsets and medical records were analyzed. Kaplan-Meier cures and log rank test were used for analyzing overall survival (OS). Univariate and multivariate survival analyses were underwent by performing the Cox proportional hazards models. Correlations were tested by Pearson’s correlation analysis.ResultsOf 122 patients, a total of 80 ccRCC patients was enrolled. Patients with low CD3+ T cells and low CD4+/CD8+ ratio displayed a worse OS than patients with high CD3+ T cells and high CD4+/CD8+ ratio (P=0.029 and 0.002, respectively). Multivariate analyses showed CD3+ T cells and CD4+/CD8+ ratio were independent predictive factors for the OS (HR: 0.295, 95% CI, 0.091–0.956; P=0.042 and HR: 0.244, 95% CI, 0.065–0.920; P=0.037, respectively). Moreover, NLR negatively correlated with both levels of CD3+ T cells and CD4+/CD8+ ratio (P<0.001, r=−0.398 and P=0.012, r=−0.280, respectively).ConclusionsThe findings of our study suggest that preoperative CD3+ T cells and CD4+/CD8+ ratio in peripheral blood are independent predictors for patients with ccRCC.

Risk Factors for Local Bone Destruction Progression in Palliative Percutaneous Vertebroplasty for Vertebral Metastases and the Significance of Bone Cement Filling Rates

BACKGROUND: For palliative percutaneous vertebroplasty (PVP) for vertebral metastases, local bone destruction progression (LBDP) commonly occurs in the previously treated vertebrae. There were no studies regarding LBDP and its risk factors in previous reports, and there was no uniform evaluation method for the distribution of bone cement in the vertebrae. OBJECTIVES: We aimed to investigate the risk factors for LBDP after PVP for palliative treatments in patients with vertebral metastases. We also proposed that filling rates could be used as a simple evaluation method to detect vertebral metastases and explored its clinical significance. STUDY DESIGN: This was a retrospective study. SETTING: A university hospital. METHODS: A total of 48 patients and 54 vertebrae that had received PVP as a palliative treatment for vertebral metastases were recruited between October 2012 to October 2019 from the Shengjing Hospital of the China Medical University. We collected and evaluated the data including age, gender, cement filled completely or not, cement dose used, the cement distribution score, time of LBDP, and so on, and the filing rate we proposed was also included. RESULTS: This retrospective study divided 48 patients and 54 vertebrae into group A for those with an LBDP of less than 6 months (n = 41), and group B for those with an LBDP of 6 or more months (n = 13). The complete filling of bone cement and bone cement dose in group B was much higher than that in group A (2.85 ± 0.97 vs. 4.12 ± 1.77; P = 0.027), and the time of recurrent pain in group B was significantly higher compared with that in group A (8.46 ± 2.73 vs. 3.39 ± 1.63; P &lt; 0.0001). There was a statistical difference in the Saliou score and filling rate between the 2 groups (11.77 ± 3.17 vs. 9.34 ± 3.28, P = 0.023; 0.752 ± 0.227 vs. 0.489 ± 0.161, P &lt; 0.0001). Univariate logistic analysis showed that complete filling of cement, the cement dose, Saliou score, and filling rate were statistically significant predictors of LBDP occurring in less than 6 months. Multivariate logistic analysis showed that the filling rate was an independent predictor of patients with vertebral metastases developing LBDP in less than 6 months (odds ratio, &lt; 0.001; 95% confidence interval, &lt; 0.001–0.006; P = 0.0007). The cutoff value for the filling rate calculated from the receiver operating characteristic (ROC) curve analysis was 0.646, which could identify patients who had LBDP in less than 6 months of PVP with a sensitivity of 85.4% and specificity of 84.6%. The 6-month LBDP in the 0.646 or less ROC curve group was higher than that in the greater than 0.646 ROC curve group (97.22% vs. 55.56%, P &lt; 0.0001). LIMITATIONS: The retrospective nature and small sample size were significant. Variation in the time and state of bone cement injected during all PVP procedures was a bias. There was no pathological diagnosis of all vertebral metastases. CONCLUSIONS: The cement dose, complete filling of cement, Saliou score, and filling rate were factors negatively related to LBDP occurring in less than 6 months. Patients with lower filling rates are maybe more likely to have early LBDP compared with those with higher filling rates. KEY WORDS: Bone cement, distribution of bone cement, local bone destruction progression, percutaneous vertebroplasty, palliative treatment, vertebral metastases

Perspectives, fears and expectations of patients with gynaecological cancers during the COVID-19 pandemic: A Pan-European study of the European Network of Gynaecological Cancer Advocacy Groups (ENGAGe).

BackgroundThe impact of the COVID‐19 pandemic on European gynaecological cancer patients under active treatment or follow‐up has not been documented. We sought to capture the patient perceptions of the COVID‐19 implications and the worldwide imposed treatment modifications.MethodsA patient survey was conducted in 16 European countries, using a new COVID‐19‐related questionnaire, developed by ENGAGe and the Hospital Anxiety & Depression Scale questionnaire (HADS). The survey was promoted by national patient advocacy groups and charitable organisations.FindingsWe collected 1388 forms; 592 online and 796 hard‐copy (May, 2020). We excluded 137 due to missing data. Median patients’ age was 55 years (range: 18–89), 54.7% had ovarian cancer and 15.5% were preoperative. Even though 73.2% of patients named cancer as a risk factor for COVID‐19, only 17.5% were more afraid of COVID‐19 than their cancer condition, with advanced age (>70 years) as the only significant risk factor for that. Overall, 71% were concerned about cancer progression if their treatment/follow‐up was cancelled/postponed. Most patients (64%) had their care continued as planned, but 72.3% (n = 892) said that they received no information around overall COVID‐19 infection rates of patients and staff, testing or measures taken in their treating hospital. Mean HADS Anxiety and Depression Scores were 8.8 (range: 5.3–12) and 8.1 (range: 3.8–13.4), respectively. Multivariate analysis identified high HADS‐depression scores, having experienced modifications of care due to the pandemic and concern about not being able to visit their doctor as independent predictors of patients’ anxiety.InterpretationGynaecological cancer patients expressed significant anxiety about progression of their disease due to modifications of care related to the COVID‐19 pandemic and wished to pursue their treatment as planned despite the associated risks. Healthcare professionals should take this into consideration when making decisions that impact patients care in times of crisis and to develop initiatives to improve patients’ communication and education.

Construction and Validation of a Novel Glycometabolism-Related Gene Signature Predicting Survival in Patients With Ovarian Cancer.

Among all fatal gynecological malignant tumors, ovarian cancer has the highest mortality rate. The purpose of this study was to develop a stable and personalized glycometabolism-related prognostic signature to predict the overall survival of ovarian cancer patients. The gene expression profiles and clinical information of ovarian cancer patients were derived from four public GEO datasets, which were divided into training and testing cohorts. Glycometabolism-related genes significantly associated with prognosis were selected. A risk score model was established and validated to evaluate its predictive value. We found 5 genes significantly related to prognosis and established a five-mRNA signature. The five-mRNA signature significantly divided patients into a low-risk group and a high-risk group in the training set and validation set. Survival analysis showed that high risk scores obtained by the model were significantly correlated with adverse survival outcomes and could be regarded as an independent predictor for patients with ovarian cancer. In addition, the five-mRNA signature can predict the overall survival of ovarian cancer patients in different subgroups. In summary, we successfully constructed a model that can predict the prognosis of patients with ovarian cancer, which provides new insights into postoperative treatment strategies, promotes individualized therapy, and provides potential new targets for immunotherapy.

Solute carrier family 12 member 8 impacts the biological behaviors of breast carcinoma cells by activating TLR/NLR signaling pathway.

This study aimed to understand the expression of solute carrier family 12 member 8 (SLC12A8) in breast carcinoma and its biological functions, as well as its effect on the Toll-like receptor /NOD-like receptor (TLR/NLR) signaling pathway. The expression of SLC12A8 was analyzed using the public RNA sequencing dataset from TCGA database and the two datasets from Oncomine database. The former dataset was also used to evaluate the prognostic value of SLC12A8 in breast carcinoma. Real-time qPCR and western blot were applied to measure relative expression of SLC12A8. Functionally, the effect of SLC12A8 on the cells proliferation and motion was studied using cell counting kit 8 and Transwell assays respectively. Mechanistic studies were conducted using Gene Set Enrichment Analysis (GSEA) and confirmed by western blot. As a result, SLC12A8 was upregulated in breast carcinoma, and high levels of SLC12A8 led to a poorer prognosis and can be regarded as an independent prognosticator for patients with breast carcinoma. Functional experiments demonstrated that SLC12A8-knockdown suppressed while SLC12A8-overexpression elevated the viability, invasiveness and motility of breast carcinoma cells. Furthermore, GSEA indicated that high SLC12A8 was positively correlated with TLR/NLR signaling pathway. Silencing SLC12A8 significantly reduced the protein expression of TLR/NLR-related markers, whereas overexpression of SLC12A8 caused an elevation on the protein expression of these markers. All these data suggested that SLC12A8 plays a promoting effect on the cells viability, invasiveness and motility in breast carcinoma by activating TLR/NLR signaling pathway.

Transmembrane protein ADAM29 facilitates cell proliferation, invasion and migration in clear cell renal cell carcinoma

Abnormal expression of ADAM29 has been frequently reported in several cancers, however, its role in clear cell renal cell carcinoma (ccRCC) has not evaluated in detail. Herein, we attempt to determine the biological role and the action mechanism of ADAM29 in ccRCC. Bioinformatics analysis based on the ccRCC RNA-Seq dataset from TCGA database revealed that ADAM29 was up-expressed in ccRCC tissues by comparison with normal tissues. And a significant increase of ADAM29 expression was also observed in 3 ccRCC cell lines (UT33A, Caki-1, and786-O) in comparison with normal cell line. Besides, high level of ADAM29 was found to be connected with the poor prognosis and could be considered as an independent prognosticator for patients with ccRCC. Furthermore, functional experiments in vitro demonstrated that ADAM29 promoted the growth, invasion and migration of ccRCC cells. Moreover, Western blot assays indicated that ADAM29 was positively correlated with the level of proliferation-related proteins Cyclin D1 and PCNA and motion-related proteins MMP9 and Snail. Our data indicate that ADAM29 acts as an oncogene that increases tumour cells proliferation, invasion and migration partly by regulating the expression of Cyclin D1/PCNA/MMP9/Snail, suggesting that ADAM29 may become a prognosticator and therapeutic candidate for ccRCC.

Clinical and pathological response to neoadjuvant chemotherapy with different chemotherapy regimens predicts the outcome of locally advanced breast cancer.

This retrospective analysis was designed to research whether clinical response partial response (PR)/complete response (CR) and pathological response (PCR) to neoadjuvant chemotherapy can translate into prognosis benefit pathological response in patients with locally advanced breast cancer and whether different chemotherapy regimens will influence the outcomes. One hundred and thirty-five patients with breast cancer patients who received neoadjuvant chemotherapy were included in the retrospective analysis. Patients were followed up strictly. Overall survival (OS) was evaluated by the Kaplan-Meier analysis. The comparison of the clinical and pathological characteristics and recurrence was performed using the carried out by chi-squared and Fisher's exact tests. Univariate and multivariate analyses were performed by the Cox regression analysis. Clinical response was strongly correlated with lymph nodes status (P=0.032). The OS comparison of pathological response between the pCR group and non-pCR groups did not exhibit statistically significant differences (P=0.400). A similar non-significant response result was observed in the comparison of clinical response between the PR/CR and SD/PD groups group (P=0.108). Univariate and multivariate analyses did not support clinical response (P=0.156 P=0.095 respectively) or pathological response (P=0.600 P=0.144 respectively) as the predictors of prognosis. There were no significant differences in either the comparison of the clinical response group it seems no statistically significance (P=0.496) or the comparison of the pathological response group (P=0.460). OS analyses across different neoadjuvant chemotherapy regimens demonstrated no significant differences (P=0.307). In the PR/CR and PD/SD comparison of every single regimen, there were no significant differences. However, for patients with PR/CR patients from the comparison of five regimens, namely, TAC, FAC, AC-T, AT and TCBP demonstrated a significant difference (P=0.022). In the group of patients with luminal A breast cancer, the result of the Fisher's exact test approached significant (P=0.059). Neither PR/CR nor pCR can translate into long-term outcome benefit. PR/CR and PCR are not independent predictors in patients with advanced breast cancer. Patients who received a taxane + anthracycline regimen exhibited a higher recurrence rate than any other regimens, especially those patients with luminal A breast cancer.

Risk of a three-year ischemic stroke recurrence and its independent predictors in patients with a confirmed manifestationof viral infection

Objective — to assess the risk of the manifest viral infection impact on the three‑year frequency of the recurrent stroke and to determine its independent predictors.Methods and subjects. From 2014 to 2019 70 patients with ischemic stroke with viral infection manifestation during 2 weeks before hospitalization were examined. The presence of viral infection was confirmed by a polymerase chain reaction (main group). A total of 220 patients without viral manifestation were included in the comparison group, who were compared with the main group by stroke severity, average age and gender. The severity of neurological deficiency was assessed by the NIHSS scale. The pathogenetic subtype of stroke was determined according to TOAST criteria.Results. Over the three‑year period, the three‑year cumulative rate of stroke recurrence was higher in main group patients — 17.4 % (non‑recurring survival 82.6 ± 4.58 %) than in comparison group — 12.1 % (non‑recurring survival 87.9 ± 2.2 %), p = 0.240. In the case of at least 2 types of viruses genomes presence in the blood, the frequency of recurrence has increased to 22.8 % (probability of non‑recurring survival 77.2 6.05 %), in comparison group — 12.1 % (probabilityofnon‑recurringsurvival 87.9 2 %), p = 0.0470. In the case of HSV1 determination, the risk of a stroke reccurence in the main group comparing to comparison group patients increased by 2.16 times: BP = 2.16; 95 % CI: 1.15 — 4.04 (p = 0.0154); HSV2 : 1.69: BP = 1.69; 95 % CI: 0.76 — 3.77 (p = 0.1983); HNV6 : 2.49: BP = 2.49; 95 % CI: 1.05 — 4.56 (p = 0.0356); CMV: 2.82: BP = 2.82; 95 % CI: 1.34 — 5.95 (p = 0.0065); EBV: 2.67 times: BP = 2.67; 95 % CI: 1.26 — 5.68 (p = 0.0106); Influenza virus: 2.64 times: BP = 2.64; 95 % CI: 1.17 — 5.95 (p = 0.0188). HSV1 (B coefficient = 4.52), CMV (B coefficient = 3.63), Influenza virus (B coefficient = 4.11), and Intima‑media thickness (B coefficient = 10.77), constant — 20.57 were determined as independent prognostic factors of a three‑year stroke recurrence in patients with viral manifestation. The predictive value of the model is high with an area of the figure under the ROC curve = 0.971, 95 % CI: 0.900 — 0.966 and model sensitivity — 100.0 %, 95 % CI: 71.5 — 100.0 % and specificity — 83.1 % (95 % CI: 71.0 — 91.6 %).Conclusions. The risk of a stroke recurrence with viral manifestation and the presence of herpes virus and influenza virus genome significantly increases in 1.89 times when two or more types of viruses are present and is 22.8 % to GP (12.1 %). The presence of HSV1, CMV DNA, influenza RNA, and Intima‑media thickness in the patient are the independent prognostic factors of a three‑year stroke recurrance in patients with viral manifestation according to the developed mathematical model using the step‑by‑step multivariant binary logistic regression.

Plaque characteristics and hemodynamics contribute to neurological impairment in patients with ischemic stroke and transient ischemic attack.

We aimed to investigate differential characteristics of plaque in the middle cerebral artery (MCA) and hemodynamics in patients with ischemic stroke and transient ischemic attack (TIA), and to develop a predictive model for the presence of ischemic stroke and neurological impairment. Sixty-seven patients with acute ischemic events in MCA territory who underwent high-resolution vessel wall imaging between September 2016 and August 2018 were reviewed retrospectively. Patients were assigned to either the stroke group or TIA group, according to diffusion-weighted imaging and neurological examination. Plaque characteristics and anterograde score (AnS) were calculated. Tmax > 6.0-s volume was acquired by RApid Processing of perfusIon and Diffusion software. Multivariate logistic regression analysis and multiple linear regression analysis were performed to establish a predictive model for irreversible infarction occurrence and clinical severity. Forty-five patients were assigned to the stroke group, and 22 were assigned to the TIA group. Plaque length, intraplaque hemorrhage (IPH), enhancement, AnS, and Tmax > 6.0-s volumes were significantly different between the two groups (p < 0.05). IPH and AnS were independent predictors for patients with stroke (p = 0.020 and 0.034, respectively). Tmax > 6.0-s volume, IPH, hypertension, and AnS were associated with high National Institutes of Health Stroke Scale (NIHSS) scores (all p < 0.05, R = 0.725, and adjusted R2 = 0.494). IPH and AnS are useful in predicting stroke occurrence. Tmax > 6.0-s volume, IPH, hypertension, and AnS are associated with neurological impairment of the patients. • Ischemic stroke and TIA patients have different plaque characteristics and hemodynamics. • Intraplaque hemorrhage and anterograde score have high diagnostic efficiency for ischemic stroke. • The combination of Tmax > 6.0-s volume, intraplaque hemorrhage, hypertension, and anterograde score can predict the National Institutes of Health Stroke Scale scores of patients.

VALUE OF ST-SEGMENT ELEVATION IN LEAD aVR IN NON STELEVATION MYOCARDIAL INFARCTION/UNSTABLE ANGINA IN PREDICTING DISEASE EXTENT, SEVERITY AND OUTCOMES.

Background: ST -segment elevation (STE) in lead aVR has been associated with three vessel disease and left main coronary stenosis in acute coronary syndrome, but prognostic relevance of this finding as an independent predictor in patients with non ST elevation myocardial infarction(NSTEMI) or unstable angina (UA) remains unknown. Methodology: We prospectively evaluated the initial electrocardiogram (ECG) in 112 patients with NSTEMI or UA. ST-elevation in lead aVR was measured. Echocardiography was performed, mitral regurgitation and left ventricular ejection fraction (LVEF) were assessed. Selective coronary angiography was performed at median of 3 days after admission, SYNTAX and Gensini scores were calculated. All the patients were followed up in hospital and 3 months after discharge. Results: Overall, 34 patients (30.3%) had STE in lead aVR (group A) and remaining 78 patients (68.7%) had NSTE (Group B). Group A patients had a higher prevalence of lateral leads ST–segment depression (p=0.001). However, group A peak troponin I (p =0.14) and LVEF ( p= 0.22) were not significantly different, but had a higher incidence of mitral regurgitation (MR) (p=0.02). The incidence of single vessel disease, double vessel disease and triple vessel disease in group A were 41%, 29.3% and 23.5%, whereas in group B they were 49%, 33.3% and 10% respectively (p=0.43, p=0.67 and p=0.06 respectively). The mean SYNTAX score was 24.56±16.43 in group A and 19.46±14.39 in group B (p = 0.47). The mean Gensini score was 64.73±40.70 in group A as compared to 46.32±39.43 in group B (p =0.53). There was no significant difference in 3 months clinical outcomes in the two groups. Conclusion: Our study showed that in NSTEMI/Unstable angina, ST elevation in aVR is associated with ST depression in lateral leads and significant MR. Readmission due to acute coronary syndromes was significantly higher in patients with STE in aVR. However, there was no significant difference in troponin I levels, LVEF, disease extent by Gensini and SYNTAX score between the two groups.

The prognostic impact of the uric acid level in patients who require cardiovascular intensive care - is serum uric acid a surrogate biomarker for critical patients in the non-surgical intensive care unit?

The prognostic impact of hyperuricemia and the factors that induce hyperuricemia in cardiovascular intensive care patients remain unclear. A total of 3257 emergency department patients were screened, and data for 2435 patients who were admitted to an intensive care unit were analyzed. The serum uric acid level was measured within 15 min of admission. The patients were assigned to a low-uric acid group (uric acid ⩽7.0 mg/dl, n=1595) or a high-uric acid group (uric acid >7.0 mg/dl, n=840) according to their uric acid level on admission. Thereafter, the patients were divided into four groups according to the quartiles of their serum uric acid level (Q1, Q2, Q3 and Q4), and uric acid levels and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. A Kaplan-Meier curve showed a significantly lower 365-day survival rate in a high-uric acid group than in a low-uric acid group, and in Q3 than in Q1 or Q2 and in Q4 than in the other groups. The multivariate logistic regression model for 30-day mortality identified Q4 (odds ratio: 1.856, 95% confidence interval (CI) 1.140-3.022; p=0.013) as an independent predictor of 30-day mortality. The area under the receiver-operating characteristic curve values of the serum uric acid level and APACHE II score for the prediction of 30-day mortality were 0.648 and 0.800, respectively. The category-free net reclassification improvement and integrated discrimination improvement showed that the calculated risk shifted to the correct direction by adding the serum uric acid level to the APACHE II score (0.204, 95% CI 0.065-0.344; p=0.004, and 0.015, 95% CI 0.005-0.025; p=0.004, respectively). The prognosis, including the 365-day mortality, among patients with a high uric acid level and a high APACHE II score was significantly poorer in comparison with other patients. The serum uric acid level, which might be elevated by the various critical stimuli on admission, was an independent predictor in patients who were emergently hospitalized in the intensive care unit. The serum uric acid level is therefore useful as a surrogate biomarker for critical patients in the intensive care unit.

Comparison of non-schistosomal colorectal cancer and schistosomal colorectal cancer

AimThe purpose of this study was to compare clinicopathological features of patients with non-schistosomal and schistosomal colorectal cancer to explore the effect of schistosomiasis on colorectal cancer (CRC) patients’ clinical outcomes.MethodsThree hundred fifty-one cases of CRC were retrospectively analyzed in this study. Survival curves were constructed by using the Kaplan-Meier (K-M) method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables.ResultsColorectal cancer patients with schistosomiasis (CRC-S) were significantly older (P < 0.001) than the patients without schistosomiasis (CRC-NS). However, there were no significant differences between CRC-S and CRC-NS patients in other clinicopathological features. Schistosomiasis was associated with adverse overall survival (OS) upon K-M analysis (P = 0.0277). By univariate and multivariate analysis, gender (P = 0.003), TNM stage (P < 0.001), schistosomiasis (P = 0.025), lymphovascular invasion (P = 0.030), and lymph nodes positive for CRC (P < 0.001) were all independent predictors in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was also an independent predictor in patients with stage III–IV tumors and in patients with lymph node metastasis, but not in patients with stage I–II tumors and in patients without lymph node metastasis.ConclusionSchistosomiasis was significantly correlated with OS, and it was an independent prognostic factor for OS in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was still an independently unfavorable prognosis factor for OS in patients with stage III–IV tumors or patients with lymph node metastasis.

&lt;p&gt;Clinicopathological Characteristics and Prognostic Factors of Patients with Gastric Cancer Accompanying Neuroendocrine Differentiation (NEDGC)&lt;/p&gt;

AimGastric carcinoma with neuroendocrine differentiation (NEDGC) is a relatively rare pathologic diagnosis in clinical practice, which has no specific guidelines or treatment recommendations yet. In this study, we aim to investigate the clinicopathological characteristics and prognostic factors of this disease.Patients and MethodsWe retrospectively analyzed clinicopathological data from a series of 82 NEDGC patients who underwent surgery for gastrectomy at Huashan Hospital Fudan University between January 2007 and December 2018. Furthermore, a series of 50 cases were used to analyze 3-year overall survival (OS).ResultsAges of the patients ranged from 26 to 83 years (M:F, 4.8:1). The majority of patients suffered from some symptoms (97.6%), as the most common one was abdominal pain (48.8%). Most of the tumors were ≥5 cm (53.7%), in the lower part of the stomach (47.5%), and with advanced T (87.8% ≥T3) and N (67.1% ≥N1) stage. As to the neuroendocrine markers, Syn showed a slight advantage on sensitivity than CgA (79.3 and 75.6%, respectively). The 3-year OS was 54%. Advanced T stage (≥T3) of the primary tumor, positive lymphovascular invasion (LVI), large tumor size (5.5cm), high neutrophil-to-lymphocyte ratio (NLR, 2.51), and low prealbumin level (173.87 mg/L) were associated with inferior OS based on the univariate analysis. Low preoperative hemoglobin level (113.87g/L), laparoscopic-assisted gastrectomy, and advanced N stage (N3) were three independent risk factors for 3-year OS of NEDGC patients in both univariate and multivariate analysis.ConclusionThe TN staging system for gastric adenocarcinoma also has a prognostic value for NEDGC patients, while N3 stage works as an independent predictor of patients’ survival. Since most of the NEDGC patients were in advanced stage, proper indications to perform operative laparoscopy should be selected.

ATP6V0D2, a subunit associated with proton transport, serves an oncogenic role in esophagus cancer and is correlated with epithelial-mesenchymal transition.

The poor prognosis of esophagus cancer (EC) is mainly due to its high invasiveness and metastasis, so it is urgent to search effectively prognostic markers and explore their roles in the mechanism of metastasis. Based on the TCGA database, we downloaded the RNA-Seq for analyzing the expression of ATP6V0D2. QRT-PCR was used to test the mRNA levels of ATP6V0D2 in cell lines. Chi-square tests were used to evaluate the correlation between ATP6V0D2 and clinical characteristics. Prognostic values were determined by Kaplan-Meier methods and cox's regression models. CCK-8 and clone formation assays were employed to evaluate the cell viability, and Transwell assay was implemented to determine the invasive and migratory abilities. Correlations between ATP6V0D2 and motion-related markers were analyzed by the GEPIA database and confirmed by western blot. Moreover, the relationship between ATP6V0D2 and molecules related to cell cycle and apoptosis was also determined by western blot. A significant increase was observed in 3 EC-related cell lines compared to the normal cell line. ATP6V0D2 has a connection with the poor prognosis and can be considered as an independent prognosticator for patients with EC. Besides, ATP6V0D2 can improve cells viability as well as invasive and migratory abilities. What's more, downregulation of ATP6V0D2 notably enhanced E-cadherin expression, while decreased N-cadherin, Vimentin, and MMP9 expression, whereas overexpression of ATP6V0D2 presented the opposite outcomes. Furthermore, we found that silencing ATP6V0D2 led to a significant reduction on the protein expression of Cyclin D1, CDK4, Bcl-2, whereas resulted in a notable enhancement on the Bax level. ATP6V0D2 might be an independent prognosticator for EC patients, and it possibly promotes tumorigenesis by regulating epithelial-mesenchymal transition, cell cycle and apoptosis-related markers, providing the possibility that ATP6V0D2 may be a novel biomarker for the therapeutic intervention of EC.

Unique metastasis-associated lncRNA signature optimizes prediction of tumor relapse in lung adenocarcinoma.

BackgroundLocal relapses and metastases are primary causes of death in lung cancer patients. In the present study, we aimed to develop a prognostic signature based on metastasis‐associated lncRNAs in patients with lung adenocarcinoma (LUAD).MethodsFirstly, the potential metastasis‐associated lncRNAs were identified by analyzing high‐throughput data from The Cancer Genome Atlas (TCGA), and based on which, an lncRNA signature was constructed for prediction of relapse in LUAD patients using Cox proportional hazards regression analysis. Moreover, the prognostic performance of the lncRNA signature was evaluated using Kaplan‐Meier survival analysis, time‐dependent receiver operating characteristic (ROC) curve and Cox analysis, respectively. In addition, the potential metastasis‐associated function of these six lncRNAs was confirmed by lncRNA over‐expression or depletion and in vitro transwell assays in LUAD cells.ResultsAn lncRNA signature consisting of six most important prognostic factors (LINC01819, ZNF649‐AS1, HNF4A‐AS1, FAM222A‐AS1, LINC02323 and LINC00672) was developed. The signature was an independent predictor for patients' relapse‐free survival (RFS), which could provide higher tumor relapse prediction capability compared with the TNM staging system at three years and five years, respectively (P = 0.0209 and P = 0.0468). Furthermore, the combination of this lncRNA signature and TNM stage had better prognostic value than TNM stage alone at three and five years, respectively (P = 0.0006 and P = 0.0096). Additionally, all the lncRNAs of the signature had a regulatory role in the LUAD cell mobility.ConclusionsThis novel six‐lncRNA signature had considerable prognostic value for prediction of relapse in LUAD patients.Key pointsSignificant findings of the studyThe unique metastasis‐associated lncRNA signature was related to tumor metastasis and prognosis in LUAD patients.What this study addsThis signature had considerable prognostic value for prediction of relapse in LUAD patients.

18F-fluorodeoxyglucose PET/CT as an independent predictor for patients with hepatocellular carcinoma combined with major portal vein tumor thrombus.

PurposeHepatocellular carcinoma (HCC) patients with major portal vein tumor thrombosis (mPVTT) complications were generally characterized by extremely poor prognoses. The aim of this study was to explore the role of 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging in predicting HCC complicated by mPVTT.MethodsFive hundred one HCC patients received surgery in our hospital during November 2008 to December 2014, among which 32 patients (6.4%) were diagnosed as HCC complicated by mPVTT. Six cases were excluded for reasons of complex medical conditions, including 2 cases of salvage liver transplantation, 2 cases of re-resection, 1 case of mPVTT combined with inferior vina cava tumor thrombosis, and 1 case of residual portal vein tumor thrombosis. Ultimately, 26 cases were enrolled in this study. The maximal tumor standardized uptake value (SUVmax) was identified as a predictive factor and detected. The univariate and multivariate regression analyses were performed to identify the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) of HCC patients complicated by mPVTT.ResultsOur results showed that the median OS was 16 months. The 1-, 3-, and 5-year cumulative OS was 55.6%, 31.7%, and 31.7%, respectively. The multivariate regression analysis revealed that SUVmax ≥ 4.65 was the only independent risk factor for RFS and OS.ConclusionSUVmax was an independent predictor for RFS and OS of patients suffering from both HCC and mPVTT. L ow SUVmax could serve as an effective factor for selecting candidates with low recurrence risks and for helping with improving patient survival after surgical resection.

Association of sclerostin with cardiovascular events and mortality in dialysis patients

Introduction Sclerostin has been reported to be a novel biomarker associated with the bone-vascular axis. In this study, we determined the relationships between serum sclerostin and all-cause mortality, the prevalence of cardiovascular events (CVEs), and coronary artery calcifications (CACs) in dialysis patients. Methods A total of 165 dialysis patients (84 hemodialysis [HD] and 81 peritoneal dialysis [PD]) were enrolled in this study. We performed multivariable linear regression analysis to test the relationships between serum sclerostin levels and demographics and clinical parameters. We also performed Cox proportional hazard regression analysis to determine independent predictors of overall survival and CVEs. Results The median serum sclerostin level was 250.9 pg/mL in dialysis patients. Kaplan–Meier analysis showed that both overall and CVE-free survival rates were significantly lower in the high serum sclerostin group (serum sclerostin level >250.9 pg/mL) compared to the low serum sclerostin group (serum sclerostin level ≤250.9 pg/mL) in patients with PD (p < 0.05). In patients with HD, only CVE-free survival rates notably declined in the high serum sclerostin group compared to the low serum sclerostin group (p = 0.029). However, serum sclerostin level was only an independent predictor of all-cause mortality and CVEs in patients with PD after adjusting for confounding factors (p < 0.05), and therefore was not an independent predictor for patients with HD (p > 0.05). Conclusions A low serum sclerostin was associated with better overall survival and lower prevalence of CVEs in patients with PD, but had no relationships in patients with HD. We found that serum sclerostin level was not correlated with CACs in either patients with HD or PD.

Abdominal aortic calcification is superior to other arteries calcification in predicting the mortality in peritoneal dialysis patients \u2013 a 8\u2009years cohort study

BackgroundIn recent years, there has been a growing concern that abdominal aortic calcification (AAC) has a predictive effect on the prognosis of patients with end-stage renal disease (ESRD). However, whether other vascular calcification (VC) can predict the occurrence of adverse events in patients, and whether it is necessary to assess the calcification of other blood vessels remains controversial. This study aimed to assess VC in different sites using X-ray films, and to investigate the predictive effects of VC at different sites on all-cause mortality and cardiovascular (CV) mortality in peritoneal dialysis (PD) patients.MethodsThe data of Radiographs (lateral abdominal plain film, frontal pelvic radiograph and both hands radiograph) were collected to evaluate the calcification of abdominal aorta, iliac artery, femoral artery, radial artery, and finger arteries. Patients’ demographic data, clinical characteristics, laboratory data were recorded. The total follow-up period was 8 years, and the time and cause of death were recorded. Survival curves were estimated using Kaplan-Meier analysis. COX regression analysis was used to examine independent predictors of all-cause mortality and CV mortality.ResultsOne hundred fifty PD patients were included, a total of 79 patients (52.7%) died at the end of follow-up. After adjusting variables in the multivariate COX regression analysis, AAC was an independent predictor of all-cause mortality in PD patients (HR = 2.089, 95% CI: 1.089–4.042, P = 0.029), and was also an independent predictor of CV mortality (HR = 4.660, 95% CI: 1.852–11.725, P = 0.001). We also found that femoral artery calcification had a predictive effect on all-cause and CV mortality. But the calcification in iliac artery, radial artery, and finger arteries were not independent predictors of patients’ all-cause and CV mortality in PD patients.ConclusionAAC was more common in PD patients and was an independent predictor of all-cause mortality and CV mortality. The femoral artery calcification also can predict the mortality, but the calcification of iliac artery, radial artery, and finger arteries cannot predict the mortality of PD patients.

Identification of Periostin as a Potential Biomarker in Gliomas by Database Mining

Bioinformatics analysis integrating microenvironmental factors and single cell analysis segregated the glioblastoma (GBM) subtype into 3 subtypes: proneural, classic, and mesenchymal. Mesenchymal GBM tends to have the worst survival but benefits from aggressive treatment protocols. Therefore, it is clinically meaningful to identify relevant biomarkers to distinguish the mesenchymal subtype. Moreover, in developing nations with limited resources, rigorous examinations are costly and inefficient for patient care. In this study, we analyzed The Cancer Genome Atlas (TCGA)-Glioblastoma and TCGA-Low-Grade Glioma RNA sequencing (RNAseq) cohorts and confirmed that the mesenchymal subtype was associated with the worst prognosis. We identified periostin (POSTN) as a mesenchymal subtype biomarker with prognostic value across histologic grades and confirmed the reliability of POSTN by gene expression meta-analysis combining TCGA, Chinese Glioma Genome Atlas (CGGA) and REMBRANDT (Repository for Molecular Brain Neoplasia Data) GBM cohorts (hazard ratio, 1.71 [range, 1.47-2.07], n= 693) and LGG cohorts (hazard ratio, 2.55 [range, 1.61-4.05], n= 1226). By using available online glioma databases, our study provided an insight into the expression of POSTN as an independent predictor for patients with glioma (GBM and LGG) and could be useful for diagnostic simplification to identify high-risk groups.