Independent Indicator Of Poor Prognosis Research Articles

Downregulation of short-stature homeobox protein 2 suppresses gastric cancer cell growth and stemness in vitro and in vivo via inactivating wnt/β-catenin signaling.

Gastric cancer (GC) a prevalent form of cancer globally. Previous research suggests that SHOX2 may have a role in promoting cancer progression. However, the role of SHOX2 in GC is not well understood. Based on data from TCGA_GC data set, SHXO2 levels were examined in normal and GC tissues. Patients in the TCGA_GC cohort were divided into high- and low-SHOX2 level groups for analysis of overall survival (OS), functional enrichment, and immune infiltration. Furthermore, experiments were conducted to investigate the impact of SHOX2 on GC cell function through gain- and loss-of-function experiments. Utilizing data from public databases, SHOX2 mRNA levels were found to be elevated in GC tissues compared to normal control, this finding was confirmed by RT-qPCR, western blot analysis, and immune-histochemical analyses. Elevated SHOX2 levels could serve as an independent indicator of poor prognosis in GC patients. Furthermore, SHOX2 levels had a negative correlation with CD8 T cells and CD4 memory activated T cells, and a positive correlation with of M0 macrophages in GC patients. Functional analyses revealed that SHOX2 deficiency notably suppressed GC cell proliferation, migration, and invasion. Additionally, SHOX2 deficiency was shown to suppress stemness in GC cells in vitro and in vivo via inactivating wnt/β-catenin signaling. Collectively, SHOX2 may serve as a prognostic marker for GC patients, and downregulation of SHOX2 could effectively impede GC cell growth and stemness by inactivating the wnt/β-catenin signaling pathway. These findings underscore the potential of SHOX2 as a promising therapeutic target for GC.

LncRNA BC200 promotes the development of EBV-associated nasopharyngeal carcinoma by competitively binding to miR-6834-5p to upregulate TYMS expression

Nasopharyngeal carcinoma (NPC) is closely related to Epstein–Barr virus (EBV) infection. Long noncoding RNAs (lncRNAs) play important roles in cancers. However, the molecular mechanism underlying the roles of lncRNAs in EBV-associated NPC remains largely unclear. In this study, we confirmed that the expression of the lncRNA brain cytoplasmic 200 (BC200) was significantly increased in EBV-infected NPC cells and tissues. BC200 facilitated the growth and migration of NPC cells, suggesting that it participated in NPC progression by functioning as an oncogene. Mechanistically, BC200 was found to act as a ceRNA by sponging and inhibiting miR-6834-5p. Thymidylate synthetase (TYMS), whose high expression was reported to be an independent indicator of poor prognosis in NPC via an unknown mechanism, was identified as a target gene of miR-6834-5p in the present study. BC200 upregulated TYMS expression in a manner that depends on miR-6834-5p. TYMS was abnormally upregulated in EBV-positive NPC cells and tissues, and its ectopic expression contributed to the proliferation and migration of NPC cells. This study highlights the role of lncRNA BC200, which is upregulated by EBV, in promoting the development of NPC, suggesting that BC200-mediated ceRNA network may be valuable biomarkers for the diagnosis and treatment of EBV-associated NPC.

IKZF3 amplification predicts worse prognosis especially in intestinal-type gastric cancer

PurposeIKAROS family zinc finger 3 (IKZF3) is an oncogene involved in different malignancies, particularly in the development and malignant progression of lymphocytes. However, IKZF3 amplification and clinical significance in gastric cancers (GCs) remain unexplored.MethodsWe examined IKZF3 amplification status in 404 GCs with HER2 amplification status using tissue microarray (TMA) and fluorescence in situ hybridization (FISH) assays.ResultsIKZF3 amplification was detected in 6.9% (28/404) of all GC patients, with higher rates in intestinal-type gastric cancer (IGC) (11.22%, 22/196) compared to other types (2.88%, 6/208). HER2 amplification was identified in 16.09% (65/404) of all GC patients, with higher rates in IGC (20.92%, 41/196) compared to other types (11.54%, 24/208). Co-amplification of IKZF3 and HER2 was detected in 8.16% (16/196) of IGC patients and in 2.40% (5/208) of other types. IKZF3 amplification showed significant correlation with IGC (P = 0.001) and HER2 amplification (P = 0.0001). IKZF3 amplification exhibited significantly worse disease-free survival (DFS) (P = 0.014) and overall survival (OS) (P = 0.018) in GC patients, particularly in IGC (DFS: P < 0.001; OS: P < 0.001), rather than other types. Cox regression analysis demonstrate IKZF3 amplification as an independent poor prognostic factor in all GCs (P = 0.006, P = 0.004 respectively) and in IGC patients, regardless of stages I-II or III-IV (P = 0.007, P = 0.004 respectively). On the other hand, HER2 amplification was significantly associated with worse DFS (P = 0.008) and OS (P = 0.01) in IGC patients, but not in all GCs and in multivariate analysis. Within the subset of patients with HER2 amplification, those also exhibiting IKZF3 amplification displayed potential poorer prognosis (P = 0.08, P = 0.11 respectively).ConclusionIKZF3 amplification was detected in minority of GC patients, especially in IGC, and was an independent indicator of poor prognosis. Our study, for the first time, found the prognostic value of IKZF3 was superior to HER2 for GC patients.

Prognostic Function and Immunologic Landscape of a Predictive Model Based on Five Senescence-Related Genes in IPF Bronchoalveolar Lavage Fluid.

Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease characterized by unknown causes and a poor prognosis. Recent research indicates that age-related mechanisms, such as cellular senescence, may play a role in the development of this condition. However, the relationship between cellular senescence and clinical outcomes in IPF remains uncertain. Data from the GSE70867 database were meticulously analyzed in this study. The research employed differential expression analysis, as well as univariate and multivariate Cox regression analysis, to pinpoint senescence-related genes (SRGs) linked to prognosis and construct a prognostic risk model. The model's clinical relevance and its connection to potential biological processes were systematically assessed in training and testing datasets. Additionally, the expression location of prognosis-related SRGs was identified through immunohistochemical staining, and the correlation between SRGs and immune cell infiltration was deduced using the GSE28221 dataset. The prognostic risk model was constructed based on five SRGs (cellular communication network factor 1, CYR61, stratifin, SFN, megakaryocyte-associated tyrosine kinase, MATK, C-X-C motif chemokine ligand 1, CXCL1, LIM domain, and actin binding 1, LIMA1). Both Kaplan-Meier (KM) curves (p = 0.005) and time-dependent receiver operating characteristic (ROC) analysis affirmed the predictive accuracy of this model in testing datasets, with respective areas under the ROC curve at 1-, 2-, and 3-years being 0.721, 0.802, and 0.739. Furthermore, qRT-RCR analysis and immunohistochemical staining verify the differential expression of SRGs in IPF samples and controls. Moreover, patients in the high-risk group contained higher infiltration levels of neutrophils, eosinophils, and M1 macrophages in BALF, which appeared to be independent indicators of poor prognosis in IPF patients. Our research reveals the effectiveness of the 5 SRGs model in BALF for risk stratification and prognosis prediction in IPF patients, providing new insights into the immune infiltration of IPF progression.

Downregulation of HIGD1B induces mitochondria-mediated apoptosis in gastric cancer cells by inactivating Akt and ERK pathways.

Gastric cancer (GC) is one of the most common malignancies worldwide. Hypoxia-inducible domain (HIGD) family members (e.g., HIGD1A) have been linked to tumor progression. However, the role of HIGD1B (another HIGD family member) in GC has yet to be fully understood. Based on data from TCGA_GC, GSE65801, and GSE65801 data sets, HIGD1B levels were evaluated in normal and GC tissues. Next, HIGD1B levels were validated by reverse transcription-quantitative PCR and western blot analysis analyses. Meanwhile, patients with GC in the TCGA_GC cohort were grouped into high- and low-HIGD1B level groups, and overall survival, functional enrichment, and immune infiltration were analyzed. Additionally, gain- and loss-of-function experiments were performed to determine the function of HIGD1B in GC cells. Compared to normal controls, HIGD1B mRNA levels were significantly elevated in GC tissues. Moreover, high HIGD1B levels may be an independent indicator of poor prognosis in patients with GC. Additionally, high HIGD1B levels were correlated with high stromal and ESTIMATE scores and elevated expression of immune checkpoints in patients with GC. Functional analyses showed that HIGD1B deficiency notably suppressed GC cell proliferation, migration, and invasion. Moreover, HIGD1B deficiency significantly induced mitochondria-mediated apoptosis in GC cells by inactivating Akt and ERK pathways. Collectively, HIGD1B may predict the prognosis of patients with GC and may function as an oncogene in GC. These findings suggest that HIGD1B may serve as a prognostic biomarker and potential therapeutic target in GC.

Single-cell analysis defines highly specific leukemia-induced neutrophils and links MMP8 expression to recruitment of tumor associated neutrophils during FGFR1 driven leukemogenesis

BackgroundLeukemias driven by activated, chimeric FGFR1 kinases typically progress to AML which have poor prognosis. Mouse models of this syndrome allow detailed analysis of cellular and molecular changes occurring during leukemogenesis. We have used these models to determine the effects of leukemia development on the immune cell composition in the leukemia microenvironment during leukemia development and progression.MethodsSingle cell RNA sequencing (scRNA-Seq) was used to characterize leukemia associated neutrophils and define gene expression changes in these cells during leukemia progression.ResultsscRNA-Seq revealed six distinct subgroups of neutrophils based on their specific differential gene expression. In response to leukemia development, there is a dramatic increase in only two of the neutrophil subgroups. These two subgroups show specific gene expression signatures consistent with neutrophil precursors which give rise to immature polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Analysis of gene expression in these precursor cells identified pathways that were specifically upregulated, the most pronounced of which involved matrix metalloproteinases Mmp8 and Mmp9, during leukemia progression. Pharmacological inhibition of MMPs using Ilomastat preferentially restricted in vitro migration of neutrophils from leukemic mice and led to a significantly improved survival in vivo, accompanied by impaired PMN-MDSC recruitment. As a result, levels of T-cells were proportionally increased. In clinically annotated TCGA databases, MMP8 was shown to act as an independent indicator for poor prognosis and correlated with higher neutrophil infiltration and poor pan-cancer prognosis.ConclusionWe have defined specific leukemia responsive neutrophil subgroups based on their unique gene expression profile, which appear to be the precursors of neutrophils specifically associated with leukemia progression. An important event during development of these neutrophils is upregulation MMP genes which facilitated mobilization of these precursors from the BM in response to cancer progression, suggesting a possible therapeutic approach to suppress the development of immune tolerance.

TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression

Abnormal Transmembrane protein 9 (TMEM9) expression has been identified in various human tumors. However, the prognostic potential and mechanistic role of TMEM9 in lung adenocarcinoma (LUAD) remain unclear. Here, we first found a significant upregulation of TMEM9 in LUAD tissues, and TMEM9 expression was positively correlated with microvessel density (MVD), T stage, and clinical stage. Survival analysis demonstrated TMEM9 was an independent indicator of poor prognosis in LUAD patients. In addition, downregulation of TMEM9 suppressed tumor growth and metastasis in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in a cancer cell/HUVEC coculture model. Furthermore, TMEM9 upregulated VEGF expression, and VEGF-neutralizing antibodies reversed HUVEC angiogenesis and cancer cell migration ability caused by overexpression of TMEM9. In contrast, recombinant VEGF (rVEGF) abolished the inhibitory effect of TMEM9-knockdown LUAD cells on HUVEC angiogenesis and tumor cell migration. Moreover, we showed that TMEM9 upregulated VEGF expression by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase/STAT3 (MEK/ERK/STAT3) pathway. Together, our study provides mechanistic insights into the role of TMEM9 in LUAD and highlights the potential of targeting the TMEM9/MEK/ERK/STAT3/VEGF pathway as a novel therapy for preventing LUAD progression.

CUL4A Ubiquitin Ligase Is an Independent Predictor of Overall Survival in Pancreatic Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with dismal prognosis. Genomic instability due to defects in cell-cycle regulation/mitosis or deficient DNA-damage repair is a major driver of PDAC progression with clinical relevance. Deregulation of licensing of DNA replication leads to DNA damage and genomic instability, predisposing cells to malignant transformation. While overexpression of DNA replication-licensing factors has been reported in several human cancer types, their role in PDAC remains largely unknown. We aimed here to examine the expression and prognostic significance of the DNA replication-licensing factors chromatin licensing and DNA replication factor 1 (CDT1), cell-division cycle 6 (CDC6), minichromosome maintenance complex component 7 (MCM7) and also of the ubiquitin ligase regulator of CDT1, cullin 4A (CUL4A), in PDAC. Expression levels of CUL4, CDT1, CDC6 and MCM7 were evaluated by immunohistochemistry in 76 formalin-fixed paraffin-embedded specimens of PDAC patients in relation to DNA-damage response marker H2AX, clinicopathological parameters and survival. We also conducted bioinformatics analysis of data from online available databases to corroborate our findings. CUL4A and DNA replication-licensing factors were overexpressed in patients with PDAC and expression of CDT1 positively correlated with H2AX. Expression of CUL4A and CDT1 positively correlated with lymph node metastasis. Importantly, elevated CUL4A expression was associated with reduced overall survival and was an independent indicator of poor prognosis on multivariate analysis. Our findings implicate CUL4A, CDT1, CDC6 and MCM7 in PDAC progression and identify CUL4A as an independent prognostic factor for this disease.

Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study.

Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (FOLFOX, CapeOX). Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic response, considering their interaction with oncogene mutations (KRAS, NRAS, PI3KCA, AKT1, BRAF). In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1, and MTHFR polymorphisms are independent indicators of poor prognosis, irrespective of oncogene mutations. BRAF wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYDrs1801265, ABCB1rs1045642, and MTHFRrs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of oncogene mutations.

Reliability and Validity of Kubios HRV Smart Phone Application as Measures of Heart Rate Variability

Introduction: Heart rate variability (HRV) analysis has given a non-invasive way for assessing cardiac autonomic control. Reduced HRV is an independent indicator of poor prognosis in both heart disease patients and the general population. Aim/Objective: To establish reliability and validity for Kubios HRV smart phone application. Materials and methods: Fifty (n =50) office workers volunteered for the study, with 10 females and 40 males ranging in age from 30 to 50 years (Mean age =38.4±5.6). To evaluate Intra and Inter-rater reliability and validity the of HRV parameter, R-R intervals comparing simultaneous recording from ECG and Kubios HRV app, at different three times (day1,day2 &amp;day3) one day apart and by two different trained examiners in the same participants. Each participants rested in supine for 10 minutes prior to the assessment and was instructed to remain relaxed, breathe properly, and refrain from talking and sleeping during the measurement. The RR intervals (R-R) were recorded during a 5 min period in supine position using ECG and polar H10 monitor with Kubios HRV smartphone application. Results: Kubios HRV smart phone application shows excellent reliability, Intra-rater (α =0.868) and Inter-rater (α =0.890) and Validity (r = 0.94) with R-R intervals calculated from ECG. Conclusion: The Kubios HRV smart phone application provides an accurate and reliable alternative to the ECG for acquiring inter-beat interval time series data. The Kubios HRV app gives an R-R interval that can be used for short term HRV analysis in office workers from steady resting conditions, supporting the selection of this approach of evaluation in research and clinical practise.

Abstract 11667: Red Cell Indices and Long-Term Prognosis of Heart Failure Patients

Introduction: It has been demonstrated that some properties of red blood cells also play a role in the etiology of cardiovascular diseases and their complications. Hypothesis: We determined to what extent red blood cell indices observed during hospitalization for heart failure (HF) affect the long-term prognosis of these patients. Methods: We followed 3697 patients [mean age 71.4 years (±SD10.1), 59.1% males] hospitalized for decompensated HF between 2010-20. In the multivariate model, we assessed the five-year all-cause mortality risk associated with red cell distribution width (RDW), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin concentration (dichotomized by tertiles). Results: Kaplan-Meier survival curves comparing the tertiles of red cell indices are in Figure. Patients with RDW in the top tertile showed roughly two-fold higher 5-year mortality risk than those in the bottom tertile; increased risk we also observed in the middle tertile of RDW. This association remained significant even after complex adjustments for individual characteristics (age, gender, ejection fraction, HF etiology, history of malignancy, revascularization, hypertension, diabetes, LDL, atrial fibrillation, and glomerular filtration) as well as treatments (furosemide, beta-blockers, RAS blockers, MRA′s, statins). [HRR 1.83 (95% CIs: 1.53-2.18), p&lt;0.0001, 3 rd versus 1 st ; 1.42 (95%CIs: 1.19-1.68), p&lt;0.0001, 2 nd versus 1 st ] Similarly, we observed increased mortality risk in the bottom tertile of MCHC [HRR 1.34 (95%CIs:1.14-1.59), p=0.001, 1 st versus 3 rd ( fully adjusted)] or hemoglobin [HRR 1.37 (95%CIs: 1.15-1.62), p&lt;0.0001]. In contrast, MCV did not show any additive mortality risk. Conclusions: High degree of anisocytosis and low red cell status of hemoglobin represents independent indicators of poor prognosis in heart failure patients, even long-term after an acute manifestation.

Evaluation and Prognosticationof Gd-EOB-DTPA MRI and CT in Patients With Macrotrabecular-Massive Hepatocellular Carcinoma.

Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is highly aggressive. Comparing the diagnosis ability of CT and gadoxetate disodium (Gd-EOB-DTPA) MRI for MTM-HCC are lacking. To compare the performance of Gd-EOB-DTPA MRI and CT for differentiating MTM-HCC from non-MTM-HCC, and determine the prognostic indicator. Retrospective. Post-surgery HCC patients, divided into the training (N = 272) and external validation (N = 44) cohorts. 3.0 T, T1-weighted imaging, in-opp phase, and T1-weighted volumetric interpolated breath-hold examination/liver acquisition with volume acceleration; enhanced CT. Three radiologists evaluated clinical characteristics (sex, age, liver disease, liver function, blood routine, alpha-fetoprotein [AFP] and prothrombin time international normalization ratio [PT-INR]) and imaging features (tumor length, intratumor fat, hemorrhage, arterial phase peritumoral enhancement, intratumor necrosis or ischemia, capsule, and peritumoral hepatobiliary phase [HBP] hypointensity). Compared the performance of CT and MRI for diagnosing MTM-HCC. Follow-up occurred every 3-6 months, and nomogram demonstrated the probability of MTM-HCC. Fisher test, t-test or Wilcoxon rank-sum test, area under the curve (AUC), 95% confidence interval (CI), multivariable logistic regression, Kaplan-Meier curve, and Cox proportional hazards. Significance level: P < 0.05. Gd-EOB-DTPA MRI (AUC: 0.793; 95% CI, 0.740-0.839) outperformed CT (AUC: 0.747; 95% CI, 0.691-0.797) in the training cohort. The nomogram, incorporating AFP, PT-INR, and MRI features (non-intratumor fat, incomplete capsule, intratumor necrosis or ischemia, and peritumoral HBP hypointensity) demonstrated powerful performance for diagnosing MTM-HCC with an AUC of 0.826 (95% CI, 0.631-1.000) in the external validation cohort. Median follow-up was 347 days (interquartile range [IQR], 606 days) for the training cohort and 222 days (IQR, 441 days) for external validation cohort. Intratumor necrosis or ischemia was an independent indicator for poor prognosis. Gd-EOB-DTPA MRI might assist in preoperative diagnosis of MTM-HCC, and intratumor necrosis or ischemia was associated with poor prognosis. 4 TECHNICAL EFFICACY: Stage 2.

Clinical Characteristics of Peripheral Lymphocyte Subtypes in Chronic Active Epstein-Barr Virus Infection.

We aimed to analyze the clinical characteristics of peripheral Epstein-Barr virus (EBV)-infected lymphocyte subtypes in children with chronic active EBV infection (CAEBV). The levels of peripheral EBV infection of CD4+ T cells, CD8+ T cells, and CD56+ natural killer (NK) cells were determined by flow cytometry and quantitative polymerase chain reaction (qPCR) in patients with CAEBV from July 2017 to July 2022. In total, 112 children with CAEBV were evaluated. Of these, CD4+ type, CD8+ type, and CD56+ type were defined in 44, 21, and 47 patients, respectively. Patients with CD8+ T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4+ T-cell type. Generally, patients with CD8+ T-cell type had the lowest overall survival rate (P = .017). Patients treated with chemotherapy and hematopoietic stem cell transplantation (HSCT) had a better prognosis (P = .001). In multivariate analysis, rash, hemophagocytic lymphohistiocytosis, CD8+ T-cell type, and no decrease of plasma EBV-DNA after treatment were independent indicators of poor prognosis (P = .002, .024, .022, and .012, respectively). In children with CAEBV, rash was more frequent in patients with CD8+ T-cell type, whereas patients with CD4+ T-cell type were more likely to develop hepatomegaly. Patients with CD8+ T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT.

Plasma lipid levels are associated with the CD8+ T-cell infiltration and prognosis of patients with pancreatic cancer.

Recently, researchers have found that the tumour microenvironment plays an important role in tumours. We aimed to investigate the effects of plasma lipids on the prognosis of patients with pancreatic cancer and the infiltration of CD8+ T lymphocytes in tumour tissue. We enrolled patients with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreatic surgery between 2012 and 2021. Clinical pathological data were recorded; total cholesterol (TC) and triglyceride (TG) levels were measured; and tissue samples were collected. A tissue microarray was generated using collected tissue samples, and CD8 staining was performed to determine immunoreactive scores (IRSs). The correlations of TC and TG levels with clinicopathological characteristics and prognosis were analysed. Finally, the correlations of TC and TG levels with CD8+ T-cell infiltration were analysed. A total of 90 eligible PDAC patients were included. TC levels were significantly correlated with tumour grade and lymph node metastasis, and TG levels were significantly correlated with perineural invasion. The Kaplan-Meier survival analysis results indicated that the prognosis in the high TC group was significantly worse than that in the low TC group, and the prognosis in the high TG group was significantly worse than that in the low TG group. Cox multivariate analysis indicated that TC was an independent indicator of poor prognosis of pancreatic cancer patients after surgery. Spearman correlation analysis indicated that there were significant negative correlations between CD8 IRS and TC and between CD8 IRS and TG. TC and TG levels are significantly related to the prognosis of pancreatic cancer patients. They may be associated with tumour progression to higher grades, lymph node metastasis and/or nerve invasion. More importantly, TC and TG may reduce CD8+ T lymphocyte infiltration into pancreatic cancer tissue, affecting antitumour immune functions and immunotherapy efficacy.

The prognostic value of C-reactive protein/albumin ratio and platelet-lymphocyte ratio in patients with pancreatic cancer.

678 Background: Pancreatic cancer is a highly malignant tumor with poor prognosis. Therefore, identification of prognostic markers is very crucial for improved risk stratification in pancreatic cancer patients. Although various systemic inflammatory markers have been investigated for their prognostic roles in pancreatic cancer, inconsistent results have been found across studies. Accordingly, the present study aimed to identify the prognostic value of inflammatory markers for patients with pancreatic cancer. Methods: The study enrolled 185 patients with pancreatic cancer. The inflammatory markers, namely, the modified Glasgow Prognostic Score (mGPS), the prognostic nutritional index (PNI), the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR), the C-reactive protein (CRP)/albumin ratio (CAR), the platelet/albumin ratio (PAR), and the CRP/lymphocyte ratio (CLR), were evaluated. Receiver operating characteristics curve analysis was performed to determine the cut-off values. The Cox proportional hazards model was used to analyze the factors affecting the prognosis. Results: The mean age of the patients was 64.1 years (with a standard deviation of 11.1), and their average overall survival (OS) was 10.5 months (95% confidence interval [CI] = 9.7–11.4). In the univariate analysis, metastatic disease, carbohydrate antigen (CA)19-9, mGPS, PNI, NLR, PLR, CAR, and CLR were significantly associated with OS ( P&lt; 0.05). In the multivariate analysis, metastatic diseases (hazard ratio [HR] = 2.52, 95% CI = 1.03–6.15, P = 0.04), CA19-9 (HR = 3.96, 95% CI = 2.01–7.79, P&lt; 0.001), PLR (HR = 2.37, 95% CI = 1.11–5.04, P = 0.03), and CAR (HR = 4.45, 95% CI = 2.19–9.03, P &lt; 0.001) were identified as independent prognostic factors for OS. Conclusions: Pretreatment PLR, CAR, CA 19-9 , and metastatic diseases were found to be independent indicators of poor prognosis in patients with pancreatic cancer. We believe that our findings will shed light on the identification of prognostic factors, which might enable a better risk stratification in pancreatic cancer patients.

Survival Impact of Postoperative Skeletal Muscle Loss in Gastric Cancer Patients Who Underwent Gastrectomy.

It has recently been recognized that preoperative sarcopenia contributes to postoperative complications and overall survival in gastric cancer (GC). However, few studies have investigated the relationship between postoperative skeletal muscle loss (SML) and survival in GC, despite the inevitability of body weight loss after gastrectomy in most GC patients. Herein, we studied the impact of postoperative SML on GC prognosis. A total of 370 patients with GC who underwent curative gastrectomy were retrospectively evaluated in this study. Postoperative SML was assessed on computed tomography (CT) images taken before surgery and 1 year after surgery. The impact of postoperative SML on survival was evaluated. Postoperative severe SML was significantly associated with presence of comorbidities, higher tumor stage, higher postoperative complication rate and longer hospital stay. Univariate and multivariate analyses of prognostic factors for overall survival revealed that SML was an independent indicator of poor prognosis, along with age, tumor stage, preoperative sarcopenia, and operation time (hazard ratio, 2.65; 95% confidence interval, 1.68-4.20, p<0.0001). There was a strong association of severe postoperative SML with decreased overall survival in patients with preoperative sarcopenia. To improve the prognosis of GC patients after surgery, it is important to prevent postoperative SML as well as preoperative sarcopenia. Perioperative multimodal interventions including nutritional counseling, oral nutritional supplements, and exercise are required to prevent SML after gastrectomy.

Impact of low and high body mass index on predicting therapeutic efficacy and prognosis in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

To evaluate the significance of both low and high body mass index (BMI) as a biomarker in first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). The oncological outcome of 235 patients with mRCC treated with TKI from 2007 to 2018 was reviewed retrospectively. All patients received first-line TKI as therapy. We analyzed the relationship between BMI (low and high) and disease control rate. The primary outcome was progression free survival and overall survival, and the association between BMI and survival prognosis was evaluated. The median BMI was 22.5 kg/m2 , and 25 patients (10.7%) had a low BMI (<18.5 kg/m2 ), 158 patients (67.2%) had a normal BMI (18.5-25 kg/m2 ), and 52 patients (22.1%) had a high BMI (≥ 25 kg/m2 ). Patients in the low BMI group had a significantly lower disease control rate, whereas patients in the high BMI group had a significantly higher disease control rate (p=0.002 and p=0.030, respectively). A log-rank test showed prognosis to be significantly poorer in the low BMI group and to be significantly better in the high BMI group than that in the normal BMI group. Multivariable Cox regression analysis showed that low BMI was an independent indicator of poor prognosis, whereas high BMI was an independent indicator of favorable prognosis. We showed the impact of both low and high BMI on predicting therapeutic efficacy and prognosis in mRCC patients treated with TKI.

The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: a systematic review and meta-analysis

IntroductionColorectal cancer is the fourth most common cancer in the UK. There remains a need for improved risk stratification following curative resection. Circulating-tumour DNA (ctDNA) has gained particular interest as a cancer biomarker in recent years. We performed a systematic review to assess the utility of ctDNA in identifying minimal residual disease in colorectal cancer.MethodsStudies were included if ctDNA was measured following curative surgery and long-term outcomes were assessed. Studies were excluded if the manuscript could not be obtained from the British Library or were not available in English.ResultsThirty-seven studies met the inclusion criteria, involving 3002 patients. Hazard ratios (HRs) for progression-free survival (PFS) were available in 21 studies. A meta-analysis using a random effects model demonstrated poorer PFS associated with ctDNA detection at the first liquid biopsy post-surgery [HR: 6.92 CI: 4.49–10.64 p < 0.00001]. This effect was also seen in subgroup analysis by disease extent, adjuvant chemotherapy and assay type.DiscussionHere we demonstrate that ctDNA detection post-surgery is associated with a greater propensity to disease relapse and is an independent indicator of poor prognosis. Prior to incorporation into clinical practice, consensus around timing of measurements and assay methodology are critical.Protocol registrationThe protocol for this review is registered on PROSPERO (CRD42021261569).

Identification and Development of an Age-Related Classification and Signature to Predict Prognosis and Immune Landscape in Osteosarcoma.

Background In childhood and adolescence, the prevailing bone tumor is osteosarcoma associated with frequent recurrence and lung metastasis. This research focused on predicting the survival and immune landscape of osteosarcoma by developing a prognostic signature and establishing aging-related genes (ARGs) subtypes. Methods The training group comprised of the transcriptomic and associated clinical data of 84 patients with osteosarcoma accessed at the TARGET database and the validation group consisted of 53 patients from GSE21257. The aging-related subtypes were identified using unsupervised consensus clustering analysis. The ARG signature was developed utilizing multivariate Cox analysis and LASSO regression. The prognostic value was assessed using the univariate and multivariate Cox analyses, Kaplan-Meier plotter, time-dependent ROC curve, and nomogram. The functional enrichment analyses were performed by GSEA, GO, and KEGG analysis, while the ssGSEA, ESTIMATE, and CIBERSORT analyses were conducted to reveal the immune landscape in osteosarcoma. Results The two clusters of osteosarcoma patients formed based on 543 ARGs, depicted a considerable difference in the tumor microenvironment, and the overall survival and immune cell infiltration rate varied as well. Among these, the selected 23 ARGs were utilized for the construction of an efficient predictive prognostic signature for the overall survival prediction. The testing in the validation group of osteosarcoma patients confirmed the status of the high-risk score as an independent indicator for poor prognosis, which was already identified as such using the univariate and multivariate Cox analyses. Furthermore, the ARG signature could distinguish different immune-related functions, infiltration status of immune cells, and tumor microenvironment, as well as predict the immunotherapy response of osteosarcoma patients. Conclusion The aging-related subtypes were identified and a prognostic signature was developed in this research, which determined different prognoses and allowed for treatment of osteosarcoma patients to be tailored. Additionally, the immunotherapeutic response of individuals with osteosarcoma could also be predicted by the ARG signature.

Mitochondrial Aconitase ACO2 Links Iron Homeostasis with Tumorigenicity in Non-Small Cell Lung Cancer.

FeS cluster-associated proteins including ACO2, mNT (encoded by CISD1), and IRP1 (encoded by ACO1) are part of an "ACO2-Iron Axis" that regulates iron homeostasis and is a determinant of a particularly aggressive subset of NSCLC.