Biomarker For Prognosis In Patients Research Articles

Consensus clustering and novel risk score model construction based on m6A methylation regulators to evaluate the prognosis and tumor immune microenvironment of early-stage lung adenocarcinoma.

The aim of this study was to investigate the correlation between m6A methylation regulators and cell infiltration characteristics in tumor immune microenvironment (TIME), so as to help understand the immune mechanism of early-stage lung adenocarcinoma (LUAD). The expression and consensus cluster analyses of m6A methylation regulators in early-stage LUAD were performed. The clinicopathological features, immune cell infiltration, survival and functional enrichment in different subtypes were analyzed. We also constructed a prognostic model. Clinical tissue samples were used to validate the expression of model genes through real-time polymerase chain reaction (RT-PCR). In addition, cell scratch assay and Transwell assay were also performed. Expression of m6A methylation regulators was abnormal in early-stage LUAD. According to the consensus clustering of m6A methylation regulators, patients with early-stage LUAD were divided into two subtypes. Two subtypes showed different infiltration levels of immune cell and survival time. A prognostic model consisting of HNRNPC, IGF2BP1 and IGF2BP3 could be used to predict the survival of early-stage LUAD. RT-PCR results showed that HNRNPC, IGF2BP1 and IGF2BP3 were significantly up-regulated in early-stage LUAD tissues. The results of cell scratch assay and Transwell assay showed that overexpression of HNRNPC promotes the migration and invasion of NCI-H1299 cells, while knockdown HNRNPC inhibits the migration and invasion of NCI-H1299 cells. This work reveals that m6A methylation regulators may be potential biomarkers for prognosis in patients with early-stage LUAD. Our prognostic model may be of great value in predicting the prognosis of early-stage LUAD.

Biomarkers associated with pulmonary exacerbations in a randomized trial of nintedanib for radiation pneumonitis

Background and purposeRadiation pneumonitis (RP) is a common side effect of thoracic radiotherapy and often has a long course characterized by acute exacerbations and progression to permanent lung fibrosis. There are no validated biomarkers of prognosis in patients diagnosed with RP. Materials and methodsWe analyzed a time course of serum chemokines, cytokines, and other proteins from patients with grade 2+ RP in a randomized clinical trial of a steroid taper plus nintedanib, a multiple tyrosine kinase inhibitor, versus placebo plus a steroid taper for the treatment of RP. Weighted gene correlation network analysis (WGCNA) and univariable zero inflated Poisson models were used to identify groups of correlated analytes and their associations with clinical outcomes. ResultsThirty enrolled patients had biomarker data available, and 17 patients had enough analytes tested for network analysis. WGNCA identified ten analytes, including transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1), and platelet-derived growth factor (PDGF), that in aggregate were correlated with the occurrence of pulmonary exacerbations (p = 0.008), the total number of acute pulmonary exacerbations (p = 0.002), and treatment arm (p = 0.036). By univariable analysis, an increase in rate of change of two components of the RP module were associated with an increased incidence rate of pulmonary exacerbations: interleukin 5 (IL-5, incidence rate ratio (IRR) 1.02, 95% CI 1.01–1.04, p = 0.002), and tumor necrosis factor superfamily 12 (TNFSF12, IRR 1.06, CI 1–1.11, p = 0.036). An increased slope of epidermal growth factor (EGF) was associated with a decreased incidence rate of exacerbations (IRR 0.94, CI 0.89–1, p = 0.036). ConclusionWe identified a panel of serum biomarkers that showed association with nintedanib treatment and acute pulmonary exacerbations in patients with RP. A confirmatory study will be needed to validate this panel for use as a prognostic tool in patients with RP.

Interaction between HOTTIP, H19, and HOTAIR long noncoding RNAs and miRNA-152 in cases of HCC caused by HCV infection

BackgroundLiver cancer (hepatocellular carcinoma “HCC”) remains a significant health issue without prompt detection and appropriate prevention. By interacting with each other, long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) can form gene regulatory networks. Specifically, we aim to determine whether the lncRNAs (HOTTIP, H19, and HOTAIR) and miRNA-152 interact in a significant manner in the progression of Hepatitis C virus (HCV) patients to HCC. This is followed by the question of whether these biomarkers can be used to diagnose and prognose noninvasively. We used online computational techniques to predict which miRNA group is likely to affect the lncRNAs being examined. This study involved 133 participants. 103 patients with HCV were included in the study, which was divided into two groups: Group I, with 65 cases of chronic liver disease without HCC, and Group II, with 38 cases of chronic liver disease with HCC. In addition, 30 healthy volunteers served as controls. In this study, a qRT-PCR was used to test gene expression.ResultsA consistent reverse correlation has been observed between lncRNAs and miRNA-152 as the disease progresses.ConclusionAccording to our findings, the studied biomarkers may be useful as noninvasive biomarkers for prognosis in patients with HCV Genotype 4 who develop liver cirrhosis and HCC. Many miRNAs, including miRNA-19a and miRNA-106a, may interact with lncRNAs that have been investigated in addition to miRNA-152.

Combined score based on plasma fibrinogen and platelet-lymphocyte ratio as a prognostic biomarker in esophageal squamous cell carcinoma

BackgroundIncreasing evidence has showed that inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and fibrinogen can be used as predictors in the prognosis of esophageal squamous cell carcinoma (ESCC). The aim of this study was to explore prognostic value of these biomarkers and evaluate the clinicopathological and prognostic significance of combined score based on plasma fibrinogen and platelet-lymphocyte ratio (F-PLR score).MethodsA total of 506 patients with ESCC were enrolled in this study. Harrell’s concordance index (c-index) was used to determine the optimal cut-off values of these markers and evaluate their prognostic significance. The relationship between factors with survival rates (including overall survival [OS] and disease-free survival [DFS]) was explored by Kaplan-Meier curve, univariate analysis and multivariate cox hazard analysis.ResultsOur result indicated that high F-PLR score was significantly associated with longer tumor length and deeper depth of tumor invasion (p < 0.01). The result of Cox multivariable analysis showed that F-PLR score was an independent prognostic factor for OS (p = 0.002) and DFS (p = 0.003). In addition, F-PLR score presented the greater c-index values for OS and DFS compared with NLR, PLR and fibrinogen level. Our result also showed that the c-index values for OS and DFS were both greater in TNM + F-PLR than those in TNM stage alone.ConclusionsIn conclusion, F-PLR score is a predictive biomarker for prognosis in patients with ESCC.

Prognostic Impact of Heat Shock Protein 90 Expression in Women Diagnosed with Cervical Cancer.

Heat Shock Protein 90 (HSP90), a major molecular chaperone, plays a crucial role in cell function by folding and stabilizing proteins and maintaining proteostasis. This study aimed to elucidate the prognostic impact of HSP90 in cervical cancer. We analyzed HSP90 expression using immunohistochemistry in cervical cancer tissue microarrays from 250 patients. This study investigated correlations between HSP90 expression levels and key clinical outcomes, including overall survival (OS), progression-free survival (PFS), and FIGO classification. The statistical analyses employed included the Kruskal-Wallis-H test, log-rank (Mantel-Cox), and Cox regression. Our findings indicate that high nuclear HSP90 expression is associated with improved OS, while high cytoplasmic HSP90 expression correlates with better PFS and a lower FIGO classification in cervical squamous cell carcinoma patients. These results suggest that HSP90 could serve as a positive prognostic factor in patients diagnosed with cervical squamous cell carcinoma, underlining its potential as a biomarker for patient prognosis and as a target for therapeutic strategies.

Circulating tumor DNA as prognostic markers of relapsed breast cancer: a systematic review and meta-analysis

ObjectiveCirculating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. MethodsPubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies; (2) patients with breast cancer; (3) ctDNA measurement; (4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. ResultsA total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50–0.83), with lower ORR in the ctDNA-positive group than ctDNA-negative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04–0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73–12.17; relapse outcome: RR = 7.11, 95% CI: 3.05–16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12–3.70; post-operative: HR = 6.03, 95% CI: 1.31–27.78). ConclusionsIn this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.

Serum caspase‑1 levels serve as a predictive biomarker for the prognosis of patients undergoing arthroscopic‑assisted locking plate internal fixation in the treatment of high‑energy pilon fractures.

The present study aimed to investigate the serum levels of caspase-1 in patients with high-energy pilon fractures, and its correlation with prognosis and clinical results. In this prospective study, 136 patients with high-energy pilon fractures who were treated with a locking plate combined with ankle arthroscopy from July 2015 to July 2020 were included. The treatment efficacy was evaluated according to the Mazur ankle function score. Serum caspase-1, interleukin (IL)-6, IL-1β and C-reactive protein (CRP) levels were measured using enzyme-linked immunosorbent assay. Reverse transcription-quantitative PCR was used to measure the mRNA expression of caspase-1. Additionally, demographic data and clinical characteristics, such as sex, age, intraoperative blood loss, fracture healing time, fracture classification and complications were collected and analyzed. The study revealed that the intraoperative blood loss, proportion of Ruedi-Allgower III and the serum levels of caspase-1 in the poor prognosis group were significantly higher compared with those in the good prognosis group. Additionally, patients with high-energy pilon fractures in the poor prognosis group exhibited significantly higher levels of caspase-1 and IL-1β serum levels at all time points in contrast to those in the good prognosis group. Spearman's analysis revealed a significant association between caspase-1, IL-1β levels and Mazur scores. Furthermore, caspase-1 could serve as a potential diagnostic biomarker for poor prognosis of patients with high-energy pilon fractures. Caspase-1, IL-1β, intraoperative blood loss and Ruedi-Allgower grade were the risk factors for poor prognosis in patients with high-energy pilon fractures. In summary, this study demonstrated that serum caspase-1 levels were progressively reduced during the treatment of high-energy pilon fractures patients and prominently lowered in those with a favorable prognosis. These findings could provide novel targets and a comprehensive approach to protecting patients with high-energy pilon fractures.

P2.21-05 CD47 as Biomarker of Prognosis in Patients with Malignant Pleural Mesothelioma

P2.21-05 CD47 as Biomarker of Prognosis in Patients with Malignant Pleural Mesothelioma

P1.23-01 ctDNA Positivity Is a Clinical Prognosis Biomarker in Patients with EGFR ex20ins+ NSCLC

P1.23-01 ctDNA Positivity Is a Clinical Prognosis Biomarker in Patients with EGFR ex20ins+ NSCLC

The sarcopenia index measured using the lumbar paraspinal muscle is associated with prognosis in endometrial cancer.

The number of type-II endometrial cancer patients has been increasing and the prognosis is not favorable. We aim to investigate whether sarcopenia index in any of several different muscles could serve as a novel biomarker of prognosis in patients with type-II endometrial cancer. We retrospectively investigated a total of 194 patients at four hospitals. Ninety patients were treated as derivation set and the other 104 patients as validation set. Using preoperative computed tomography images, we measured the horizontal cross-sectional area at the third lumbar spine level: the (i) psoas major, (ii) iliac and (iii) paraspinal muscle. The clinical information including recurrence-free survival and overall survival were retrospectively collected. These results were validated with external data sets of three hospitals. The median values of the sarcopenia index (cm2/m2)±standard deviation with the first data of 90 patients using the psoas, iliac and paraspinal muscle were 3.4±1.0, 1.7±0.6 and 12.6±3.2, respectively. In univariate analyses, the sarcopenia indexes measured using the psoas or paraspinal muscle were associated with recurrence-free survival and overall survival. On the other hand, in multivariate analyses, only the sarcopenia index using paraspinal muscle was significantly related to recurrence-free survival (hazard ratio = 3.78, 95% confidence intervals = 1.29-5.97, P=0.009) and overall survival (hazard ratio=3.13, 95% confidence interval = 1.18-8.26, P=0.022). Paraspinal sarcopenia index was also related to overall survival (hazard ratio=3.74, 95% confidence interval = 1.31-10.72, P=0.014) even in patients with advanced stage. Serum albumin was significantly correlated with the sarcopenia index (P=0.012). Within the analysis of the validation set, sarcopenia index using paraspinal muscle was related to recurrence-free survival (hazard ratio=2.06, P=0.045) in multivariate analysis and recurrence-free survival (P=0.009) in patients with advanced stage. The sarcopenia index using the paraspinal muscle, not psoas, could be a suitable index to predict recurrence-free survival and overall survival in patients with type-II endometrial cancer even in advanced stage.

Development of a novel copper metabolism-related risk model to predict prognosis and tumor microenvironment of patients with stomach adenocarcinoma.

Background: Stomach adenocarcinoma (STAD) is the fourth highest cause of cancer mortality worldwide. Alterations in copper metabolism are closely linked to cancer genesis and progression. We aim to identify the prognostic value of copper metabolism-related genes (CMRGs) in STAD and the characteristic of the tumor immune microenvironment (TIME) of the CMRG risk model. Methods: CMRGs were investigated in the STAD cohort from The Cancer Genome Atlas (TCGA) database. Then, the hub CMRGs were screened out with LASSO Cox regression, followed by the establishment of a risk model and validated by GSE84437 from the Expression Omnibus (GEO) database. The hub CMRGs were then utilized to create a nomogram. TMB (tumor mutation burden) and immune cell infiltration were investigated. To validate CMRGs in immunotherapy response prediction, immunophenoscore (IPS) and IMvigor210 cohort were employed. Finally, data from single-cell RNA sequencing (scRNA-seq) was utilized to depict the properties of the hub CMRGs. Results: There were 75 differentially expressed CMRGs identified, 6 of which were linked with OS. 5 hub CMRGs were selected by LASSO regression, followed by construction of the CMRG risk model. High-risk patients had a shorter life expectancy than those low-risk. The risk score independently predicted STAD survival through univariate and multivariate Cox regression analyses, with ROC calculation generating the highest results. This risk model was linked to immunocyte infiltration and showed a good prediction performance for STAD patients' survival. Furthermore, the high-risk group had lower TMB and somatic mutation counters and higher TIDE scores, but the low-risk group had greater IPS-PD-1 and IPS-CTLA4 immunotherapy prediction, indicating a higher immune checkpoint inhibitors (ICIs) response, which was corroborated by the IMvigor210 cohort. Furthermore, those with low and high risk showed differential susceptibility to anticancer drugs. Based on CMRGs, two subclusters were identified. Cluster 2 patients had superior clinical results. Finally, the copper metabolism-related TIME of STAD was concentrated in endothelium, fibroblasts, and macrophages. Conclusion: CMRG is a promising biomarker of prognosis for patients with STAD and can be used as a guide for immunotherapy.

Mutant-allele dispersion correlates with prognosis risk in patients with advanced non-small cell lung cancer.

Intra-tumor heterogeneity (ITH) contributes to lung cancer progression and resistance to therapy. To evaluate ITH and determine whether it may be employed as a predictive biomarker of prognosis in patients with advanced non-small cell lung cancer (NSCLC), we used a novel algorithm called mutant-allele dispersion (MAD). In the study, 103 patients with advanced NSCLC were enrolled. Using a panel of 425 cancer-related genes, next-generation sequencing (NGS) was performed on tumor specimens that had been collected. From NGS data, we derived MAD values, and we next looked into their relationships with clinical variables and different mutation subtypes. The median MAD among 103 NSCLC patients was 0.73. EGFR mutation, tyrosine kinase inhibitor (TKI) therapy, radiotherapy, and chemotherapy cycles were all substantially correlated with the MAD score. In patients with lung adenocarcinoma (LUAD), correlation analysis revealed that the MAD score was substantially linked with Notch pathway mutation (P = 0.021). A significant relationship between high MAD and shorter progression-free survival (PFS) was found (HR = 2.004, 95%CI 1.269-3.163, P = 0.003). In patients with advanced NSCLC, histological type (P = 0.004), SMARCA4 mutation (P = 0.038), and LRP1B mutation (P = 0.006) were all independently associated with prognosis. The disease control rate was considerably greater in the low MAD group compared to the high MAD group in 19 LUAD patients receiving immunotherapy (92.9% vs. 40%, P = 0.037). TKI-PFS was longer in 37 patients with low MAD who received first-line TKI therapy (P = 0.014). Our findings suggested that MAD is a practical and simple algorithm for assessing ITH, and populations with high MAD values are more likely to have EGFR mutations. MAD can be used as a potential biomarker to predict not only the prognosis of NSCLC but also the efficacy of immunotherapy and TKI therapy in patients with advanced NSCLC.

A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease.

The cytoskeletal protein ezrin is upregulated in many cancer types and is strongly associated with poor patient outcome. While the clinical and prognostic value of ezrin has been previously evaluated in breast cancer, most studies to date have been conducted in smaller cohorts (less than 500 cases) or have focused on specific disease characteristics. The current study is the largest of its kind to evaluate ezrin both at the protein and mRNA levels in early-stage breast cancer patients using the Nottingham (n=1094) and METABRIC (n=1980) cohorts, respectively. High expression of ezrin was significantly associated with larger tumour size (p=0.027), higher tumour grade (p < 0.001), worse Nottingham Prognostic Index prognostic group (p=0.011) and HER2-positive status (p=0.001). High ezrin expression was significantly associated with adverse survival of breast cancer patients (p < 0.001) and remained associated with survival in multivariate Cox-regression analysis (p=0.018, hazard ratio (HR)=1.343, 95% confidence interval (CI)=1.051-1.716) when potentially confounding factors were included. High ezrin expression was significantly associated with adverse survival of patients whose tumours were categorised as receptor (oestrogen receptor (ER), progesterone receptor (PgR) or HER2) positive (p < 0.001) in comparison to those categorised as triple-negative breast cancer (p=0.889). High expression of ezrin mRNA (VIL2) in the METABRIC cohort was also significantly associated with adverse survival of breast cancer patients (p < 0.001). Retrospective analyses show that ezrin is an independent prognostic marker, with higher expression associated with shortened survival in receptor-positive (ER, PgR or HER2) patients. Ezrin expression is associated with more aggressive disease and may have clinical utility as a biomarker of patient prognosis in early-stage breast cancer.

Analysis of plasma circulating tumor DNA in borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant modified FOLFIRINOX: Clinical relevance of DNA damage repair gene alterations.

737 Background: There is no reliable biomarker to guide treatment for patient with borderline resectable pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant modified (m)FOLFIRINOX. We investigated the role of plasma circulating tumor DNA (ctDNA) sequencing to discover potential biomarkers for patients treated with neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (ClinicalTrials.gov identifier: NCT02749136). Methods: Among 44 patients enrolled in the trial, patients with plasma ctDNA analysis performed at baseline or post-operative period were included in the analysis. Plasma cell-free DNA isolation and sequencing of ctDNA were performed using the Guardant 360 assay. Association of clinical outcomes with germline or somatic mutations of DNA damage repair (DDR) genes was analyzed. Somatic alterations other than DDR genes were also analyzed to find potential biomarkers of neoadjuvant mFOLFIRINOX. Progression free-survival (PFS) was defined as time from the initiation of mFOLFIRINOX to disease progression or any cause of death. Overall survival (OS) was defined as the time from the initiation of mFOLFIRINOX to any cause of death. Results: Among 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study (15 patients with baseline data only, 3 patients with post-operative data only, and 10 patients with both baseline and post-operative data). Median age was 59 (range, 41-73) years and 15 patients (53.6%) were male. Among 25 patients with baseline plasma ctDNA data, 11 patients (44%) had somatic or germline alteration of DDR genes detected at baseline including ATM, BRCA1, BRCA2 and MLH1, and showed significantly better PFS than those without such DDR gene alterations (median 26.6 vs. 13.5 months, log-rank p = 0.004). Although there was a trend for better OS in patients with DDR gene alterations, this was not statistically significant (log-rank p = 0.29). The most observed baseline somatic alteration was TP53 (n = 7, 28%), followed by KRAS (n = 6, 24%). Patients with somatic KRAS mutation at baseline had significantly worse OS (median 8.5 months vs. not applicable, log-rank p = 0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, 8 patients (61.5%) had detectable somatic alterations. Conclusions: Detection of germline or somatic mutations of DDR genes from plasma ctDNA at baseline was associated with better survival outcomes of patients with borderline resectable PDAC treated with neoadjuvant mFOLFIRINOX. Detection of DDR gene alterations from plasma ctDNA may have a potential role as biomarker for prognosis in patients with borderline resectable PDAC treated with mFOLFIRINOX.

TREM2 as a Potential Immune-Related Biomarker of Prognosis in Patients with Skin Cutaneous Melanoma Microenvironment.

The skin cutaneous melanoma (SKCM) is a devastating form of skin cancer triggered by genetic and environmental factors, and the incidence of SKCM has rapidly increased in recent years. Immune infiltration of the tumor microenvironment is positively associated with overall survival in many tumors. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although numerous evidences suggest a crucial role for TREM2 in tumorigenesis of some tumors, no systematic SKCM analysis of TREM2 is available. Mehods. The relationship between TREM2 expression and diagnostic and prognostic value of SKCM patients via using The Cancer Genome Atlas (TCGA) data. The expression level of TREM2 and clinical characteristic correlation in SKCM patients were assessed by the Wilcoxon rank sum test. The cox regression methods, Kaplan-Meier (KM), and log-rank test were used to assess the impact of TREM2 expression on the overall survival (OS). Furthermore, the Gene Set Enrichment Analysis (GSEA) and TIMER were performed to evaluate the enrichment pathways and potential functions and quantify the immune cell infiltration level for TREM2 expression. The TREM2 in SKCM sample expression levels was significantly higher than in normal tissues. Moreover, this expression level of TREM2 was also associated with the BMI of SKCM patients. KM overall survival analysis and OS curve displayed that a high-level TREM2 expression was significantly correlated with a better SKCM prognosis of patients as compared with a low level of TREM2 expression. The GSEA analysis also revealed that TREM2 was associated with immune functions, such as neutrophil activation. TREM2 played a crucial role in SKCM, which might be a prognostic biomarker and correlated with immune infifiltrates in SKCM patients.

Determination of HMGB1 in hepatitis B virus-related acute-on-chronic liver failure patients with acute kidney injury: Early prediction and prognostic implications.

Background: Acute kidney injury (AKI) is a frequent complication in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and is associated with high rates of mortality. We aimed to estimate serum high mobility group protein 1 (HMGB1) levels in hepatitis B virus-related acute-on-chronic liver failure patients and analyze their clinical value in the development and outcomes of Acute kidney injury. Methods: A total of 251 consecutive patients with hepatitis B virus-related acute-on-chronic liver failure were enrolled in this retrospective study. Using the International Club of Ascites staging criteria of Acute kidney injury, 153 patients developed Acute kidney injury. The clinical data of patients were collected and serum levels of high mobility group protein 1 were measured by ELISA. All patients were followed up until death or for a minimum of 3months. Early prediction and prognostic implications of high mobility group protein 1 in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Patients with Acute Kidney Injury were investigated in different cohorts, including a propensity score-matched ACLF cohort. Results: Among all individuals with hepatitis B virus-related acute-on-chronic liver failure, the incidence of Acute kidney injury was 61.0% (153/251). The patients who developed stage 2/3 Acute kidney injury showed the highest high mobility group protein 1 levels, followed by those who developed stage 1 Acute kidney injury, and those without Acute kidney injury showed the lowest high mobility group protein 1 levels. Moreover, high mobility group protein 1 levels were significantly higher in non-survivors than in survivors among hepatitis B virus-related acute-on-chronic liver failure patients with Acute kidney injury. Furthermore, analysis of the area under the receiver operating characteristic curve (AUROC) indicated that serum high mobility group protein 1 levels (pre-matching: AUC = 0.740; post-matching: AUC = 0.661) may be a potential predictive factor for Acute kidney injury development and that high mobility group protein 1 (AUC = 0.727) might be a reliable biomarker for prognosis in patients with Acute kidney injury. Conclusion: In patients with hepatitis B virus-related acute-on-chronic liver failure, Acute kidney injury is universal. Acute kidney injury and its stages negatively influence the 90-day transplant-free mortality rate. Serum high mobility group protein 1 levels can serve as a positive predictor of Acute kidney injury development, and high mobility group protein 1 might also be a prognostic biomarker for Acute kidney injury among hepatitis B virus-related acute-on-chronic liver failure patients.

Metabolic parameters on baseline 18F-FDG PET/CT are potential predictive biomarkers for immunotherapy in patients with head and neck squamous cell carcinoma.

PurposeWe evaluated baseline 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters for predicting prognosis in patients with head and neck squamous cell carcinoma (HNSCC) who were receiving immune checkpoint inhibitors (ICIs). In addition, we also investigated the relationships between immunohistochemical (IHC) biomarkers and metabolic parameters.Materials and methodsA total of 39 patients with HNSCC who underwent 18F-FDG PET/CT prior to ICI therapy between November 2015 and December 2020 were enrolled. PET parameters of tumor lesions included standardized uptake values, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and spleen-to-liver ratio (SLR). Clinical variables, IHC markers, and derived neutrophil-to-lymphocyte ratio (dNLR) were also obtained. Analysis was performed using Cox proportional hazard model, Kaplan-Meier method with log-rank test, and Spearman's correlation.ResultsTotal MTV (TMTV), total TLG (TTLG), and a combined parameter consisting of TMTV and dNLR were significant predictors for progression-free survival (PFS) in univariable analysis (TMTV, p = 0.018; TTLG, p = 0.027; combined parameter, p = 0.021). Above all, the combined parameter was an independent prognostic factor for PFS in multivariable analysis. The group with low TMTV and low dNLR had longer PFS than the group with high TMTV and high dNLR (p = 0.036). SLR was the only significant predictor for overall survival (p = 0.019). Additionally, there was a negative correlation between programmed cell death-ligand 1 expression (one of the IHC markers) and MTV in subgroup analysis.ConclusionPET parameters on baseline 18F-FDG PET/CT were predictive biomarkers for prognosis in patients with HNSCC undergoing ICI therapy. With dNLR, more accurate prognostic prediction could be possible.

Body Composition as a Predictor of the Survival in Anal Cancer.

Simple SummaryObesity and overweight are major health hazards in general and for cancer patients in specific. In this study, we used two parameters for measuring obesity, namely body mass index (BMI) and visceral-to-subcutaneous fat ratio (VSR), to evaluate the effect of obesity on the survival of patients with cancer of the anus. Our results show that obese patients live shortly compared to patients without obesity. Measures to counter obesity at the time of diagnosis could be necessary to improve the outcomes of treatment.Background and aim: Sarcopenia and body composition parameters such as visceral and subcutaneous adipose tissue and visceral-to-subcutaneous adipose tissue ratio have been shown to be relevant biomarkers for prognosis in patients with different types of cancer. However, these findings have not been well studied in anal cancer to date. Therefore, the aim of this study was to evaluate the prognostic value of different body composition parameters in patients undergoing radiation therapy for the treatment of anal cancer with curative intent. Material and Methods: After approval by the institutional ethical committee, we retrospectively identified 81 patients in our local registry, who received radical intensity-modulated radiotherapy for the management of anal squamous cell cancer (ASCC). Clinical information, including body mass index (BMI), survival, and toxicities outcome, were retrieved from the local hospital registry. Based on the pre-therapeutic computer tomography (CT), we measured the total psoas muscle area, visceral adipose tissue area (VAT), subcutaneous adipose tissue area (SAT), and visceral-to-subcutaneous adipose tissue area ratio (VSR). In addition to the classical prognostic factors as T-stage, N-stage, gender, and treatment duration, we analyzed the impact of body composition on the prognosis in univariate and multivariate analyses. Results: Sarcopenia was not associated with increased mortality in anal cancer patients, whereas increased BMI (≥27 kg/m2) and VSR (≥0.45) were significantly associated with worsened overall survival and cancer-specific survival in both univariate and multivariate analyses. VSR—not BMI—was statistically higher in males. Sarcopenia and VSR ≥ 0.45 were associated with advanced T-stages. None of the body composition parameters resulted in a significant increase in treatment-related toxicities. Conclusion: BMI and visceral adiposity are independent prognostic factors for the survival of patients with anal cancer. Measurements to treat adiposity at the time of diagnosis may be needed to improve the survival outcomes for the affected patients.

Characteristics of Albumin Levels and Liver Function in Patients With COVID-19 at H. Adam Malik Hospital, Medan

Background: COVID-19 (Corona Virus Disease-2019) pandemic has a high mortality rate especially in Medan, Indonesia. Serum albumin and liver function tests are believed to be predictive biomarkers for prognosis in patients with infectious diseases, including COVID-19. This study aimed to investigate the association between the mortality events and severely ill COVID-19 patients' serum albumin and liver enzymes. Method: This is a cross-sectional study using secondary data from the medical records of H. Adam Malik Hospital patients with COVID-19 who were confirmed by RT-PCR from August to December 2020. All patients were analyzed for age, sex, hypoalbuminemia, increased liver enzymes and outcome using Chi-square tests (P&lt;0.05). Results: The average age of severe COVID-19 patients at H. Adam Malik Hospital ranged from 41 to 60 years, with more women prevalence than men. Most of the patients had hypoalbuminemia (84.2%), an increase in AST (59.4)% and ALT (45.5%). There was no significant association between hypoalbuminemia and the disease outcome (P=0.12). There was a significant association between elevated liver enzymes and mortality in severely ill COVID-19 patients (P&lt;0.001). Conclusion: We found that hypoalbuminemia is common in patients with severe COVID-19. However, we found that albumin levels had no association with the patients' mortality rate. Liver enzymes levels appear to be a predictive biomarker for outcomes in COVID-19 patients of H. Adam Malik Hospital. We found that higher ALT and AST levels were associated with significantly higher mortality.

Correlation of vascular endothelial growth factor with survival and pathological characteristics of patients with osteosarcoma: A systematic review and meta‐analysis

This study aimed to assess the prognostic role of vascular endothelial growth factor (VEGF) expression in osteosarcoma. Systematic searches of PubMed, Embase, CINAHL, Cochrane Library, ScienceDirect, and Web of Science were conducted. The correlation between VEGF expression and patients' survival was our primary endpoint. The secondary endpoints were the associations between VEGF level and patients' sociodemographic and pathological characteristics. The pooled hazard ratio (HR) or odd ratio (OR) and corresponding 95% confidence intervals (CIs) were obtained to assess the associations between VEGF expression and the target factors. Subgroup and meta-regression analyses were conducted to explore potential factors that associated with VEGF efficacy. The combined HR suggested that a positive VEGF status has a negative impact on overall survival (OS) (HR = 2.58; 95% CI, 2.09-3.19; P < 0.0001) and disease-free survival (DFS) (HR = 2.54; 95% CI, 1.84-3.50; P < 0.0001) in patients with osteosarcoma. Meta-regression analysis ruled out the influence of cut-off value, disease stage, histological subtype, disease grade, tumour location, geographic area, publication year, and method of HR acquisition on heterogeneity. Results showed that VEGF expression was closely correlated with tumour staging, chemotherapy response, and metastasis. Based on the study results, VEGF could serve as an effective biomarker of prognosis in patients with osteosarcoma. Besides, VEGF was related to increased tumour malignancy, which might help guide clinical decision-making regarding therapy and outcomes.