Valuable Prognostic Biomarker Research Articles

Prognostic Nutritional Index is a valuable preoperative prognostic biomarker in Mexican patients surgically intervened on gastrointestinal stromal tumors: a retrospective cohort study.

The immunonutritional status of cancer patients has a profound impact on lifespan. Prognostic Nutritional Index (PNI) evaluates prognosis in operated patients with both neoplastic and non-neoplastic conditions. This study estimates the overall survival (OS) of Mexican patients operated on gastrointestinal stromal tumors (GIST) based on PNI. Immune-nutritional status was retrospectively analyzed in a cohort of 104 patients operated on GIST. Receiver operating characteristic (ROC) curves and X-tile software were used to estimate the optimal cutoff point and predict OS stratifying patients by PNI. Survival curves were obtained through Kaplan-Meier and log-rank methods. Multivariate analysis of survival was performed by Cox regression. PNI (≥ 36.5) (p = 0.024) and mitotic index (≥ 5) (p = 0.013) were the only independent prognostic scores; the PNI-high group had better survival with 81.5% less risk of death (HR = 0.185). High PNI was correlated with favorable characteristics, i.e., low/intermediate risk (p = 0.046), reduced mitotic index (< 5) (p = 0.001), and younger age (< 55years, p = 0.047). PNI ≥ 36.5 entails a better prognosis for Mexican patients with surgically resected GIST. PNI represents a simple, reliable, and cost-effective prognostic tool, besides the pathological approach.

Predicting Severe COVID-19 Outcomes in the Elderly: The Role of Systemic Immune Inflammation, Liver Function Tests, and Neutrophil-to-Lymphocyte Ratio.

Background: Patients aged 80 years and above are at increased risk for severe COVID-19 outcomes. This study aimed to evaluate the prognostic utility of the derived neutrophil-to-lymphocyte ratio (dNLR), aspartate-aminotransferase-to-lymphocyte ratio index (ALRI), aspartate-aminotransferase-to-platelet ratio index (APRI), and systemic immune inflammation index (SII) in predicting severe disease, intensive care unit (ICU) admission, and mortality among COVID-19 patients aged 80 years and older. Methods: In this retrospective cohort study, 138 elderly patients (≥80 years) and 215 younger controls (<65 years) with confirmed COVID-19 were included. Laboratory data at admission were collected, and the dNLR, ALRI, APRI, and SII scores were calculated. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of these indices. Results: The SII had the highest area under the ROC curve (AUC) for predicting severe disease in elderly patients (AUC = 0.857, 95% CI: 0.795-0.919, p < 0.001), with an optimal cutoff value of 920 × 10⁹/L (sensitivity 86%, specificity 78%). Elevated SII was significantly associated with increased risk of ICU admission (hazard ratio (HR): 2.9, 95% CI: 1.8-4.6, p < 0.001) and mortality (HR: 3.2, 95% CI: 1.9-5.2, p < 0.001). Similarly, dNLR showed good predictive value (AUC = 0.792, 95% CI: 0.722-0.862, p < 0.001). Conclusions: SII and dNLR are valuable prognostic biomarkers for predicting severe outcomes in COVID-19 patients aged 80 years and above. Early identification using these indices can assist clinicians in risk stratification and management decisions to improve patient outcomes.

Exon 1 methylation status of CDH13 is associated with decreased overall survival and distant metastasis in patients with postoperative colorectal cancer

BackgroundCadherin 13 (CDH13) is a member of the cadherin superfamily that exerts tumor-suppressive effects on cancers derived from epithelial cells. Although hypermethylation of CDH13 promoter has been reported in various cancers, its prognostic value for colorectal cancer (CRC) is still controversial. The methylation alterations of CDH13 within exon 1 have not yet been investigated.MethodsA total of 49 CRC patients were recruited for the prospective study. The methylation status of CpG sites was quantified by Bisulfite Amplicon Sequencing (BSAS) in malignant tissues and adjacent normal tissues. The primary endpoint of the study was overall survival (OS) after surgery. The relationship between methylation level with pathological stage and OS was also evaluated.ResultsCompared with adjacent normal tissues, the overall average methylation level within exon 1 was significantly increased in tumor tissues (p < 0.001). The association study showed that the hypermethylation status of the CpG1 site was non-significantly associated with the presence of distant metastasis (p = 0.032). Moreover, the hypermethylation of two CpG sites, including CpG1 (p = 0.003) and CpG5 (p = 0.032), was associated with worse OS in CRC. Co-hypermethylation of CpG1 and CpG5 sites was significantly associated with a worse clinical outcome (HR: 4.43 [95% CI 1.27–15.46]; p = 0.019) in multivariate Cox regression analysis.ConclusionThe methylation level of CDH13 exon 1 in CRC tissue was significantly higher than in adjacent normal tissues. Hypermethylation at the CpG1 site suggests a risk of distant metastasis in CRC. The hypermethylation of the CpG1 site and CpG5 site, including the co-hypermethylation of these two sites, may serve as a valuable prognostic biomarker.

An Integrated Framework to Identify Prognostic Biomarkers and Novel Therapeutic Targets in Hepatocellular Carcinoma-Based Disabilities

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors globally, significantly affecting liver functions, thus necessitating the identification of biomarkers and effective therapeutics to improve HCC-based disabilities. This study aimed to identify prognostic biomarkers, signaling cascades, and candidate drugs for the treatment of HCC through integrated bioinformatics approaches such as functional enrichment analysis, survival analysis, molecular docking, and simulation. Differential expression and functional enrichment analyses revealed 176 common differentially expressed genes from two microarray datasets, GSE29721 and GSE49515, significantly involved in HCC development and progression. Topological analyses revealed 12 hub genes exhibiting elevated expression in patients with higher tumor stages and grades. Survival analyses indicated that 11 hub genes (CCNB1, AURKA, RACGAP1, CEP55, SMC4, RRM2, PRC1, CKAP2, SMC2, UHRF1, and FANCI) and three transcription factors (E2F1, CREB1, and NFYA) are strongly linked to poor patient survival. Finally, molecular docking and simulation identified seven candidate drugs with stable complexes to their target proteins: tozasertib (−9.8 kcal/mol), tamatinib (−9.6 kcal/mol), ilorasertib (−9.5 kcal/mol), hesperidin (−9.5 kcal/mol), PF−562271 (−9.3 kcal/mol), coumestrol (−8.4 kcal/mol), and clofarabine (−7.7 kcal/mol). These findings suggest that the identified hub genes and TFs could serve as valuable prognostic biomarkers and therapeutic targets for HCC-based disabilities.

Pan-cancer analysis of STAT3 indicates its potential prognostic value and correlation with immune cell infiltration in prostate cancer

BackgroundTargeting the STAT3 signaling pathway is a promising therapeutic approach for cancer patients. However, the association between STAT3 expression, the tumor immune microenvironment, and genetic variation remains unclear across human cancers, especially prostate cancer.MethodsWe used R software and other tools to analyze pan-cancer and mutation data from publicly available databases statistically. A comprehensive investigation was performed to assess the genetic heterogeneity and clinical relevance of STAT3 in various malignancies, with a specific focus on its role in the immune landscape and prognostic significance in prostate cancer. The findings were validated through immunohistochemistry (IHC) and multiplex immunofluorescence (mIF).ResultsSTAT3 expression is abnormal in the majority of cancer tissues, which is strongly correlated with these patients' prognosis. Eight measures of tumor heterogeneity and six measures of tumor stemness of multiple tumor types showed a strong correlation with STAT3 expression. Furthermore, in individuals with prostate cancer, STAT3 expression indicated the degree of immune cell infiltration and the advancement of the disease. IHC analysis revealed that STAT3 was down-regulated in prostate tumor tissues, while mIF analysis demonstrated that STAT3 signaling (p-STAT3) was extensively active in tumor tissues and positive lymph node tissues.ConclusionSTAT3 may serve as a valuable prognostic biomarker and therapeutic target across various cancers, with particular relevance to prostate cancer.

Design of buffer property for the new enrichment method of circulating tumor cell based on immunomagnetic-negative separation

Metastasis is a significant contributor to cancer-related mortality and a critical issue in cancer. Monitoring the changes in circulating tumor cells (CTCs) with metastatic potential is a valuable prognostic and predictive biomarker. CTCs are a rare population in the peripheral blood of patients with cancer. The enrichment process is extremely important for the isolation of clinically significant CTC subpopulations, which can then be used for further analysis. The present study postulates that the buffer serves as an essential field for immunomagnetic separation, thereby enhancing the efficacy of CTC enrichment in peripheral blood. This, in turn, facilitates CTC detection. Here, we describe the design of buffers for developing a novel immunomagnetic-negative separation method for CTC enrichment. During the design process, the buffer properties of the floating and cell coatings had a synergistic effect on the efficiency of cell enrichment in blood samples. The efficacy of the method was evaluated using peripheral blood samples from patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The developed method enriched clinically relevant CTC subpopulations that expressed the epithelial-mesenchymal transition (EMT)-related molecule vimentin and/or the cancer immune checkpoint marker programmed death ligand 1 (PD-L1). Furthermore, it was applicable as a part of the enrichment process in a TelomeScan® (OBP-401)-based CTC detection assay with high sensitivity and specificity. From the perspective of methodological approaches, the design of buffer properties can be useful for developing a highly versatile enrichment method for handling CTC heterogeneity.

Serum endocan (ESM-1) as diagnostic and prognostic biomarker in Multisystem inflammatory syndrome in children (MIS-C)

Endothelial-cell-specific molecule-1 (ESM-1) also called endocan is a well-known biomarker for detecting inflammation, endothelial dysfunction (ED), and cardiovascular (CV) risk in COVID-19 patients. Upon SARS-CoV-2 infection, a small percentage of children develop Multisystem Inflammatory Syndrome in children (MIS-C). Whether endocan can be used as a biomarker of MIS-C is unknown. In this study, we assessed ESM-1 levels in MIS-C (n = 19) and healthy controls (HC; n = 17). We observed a significant increase in serum ESM-1 levels in MIS-C vs HC (p = 0.0074). In addition, ROC curve analysis demonstrated that this factor has a reasonable discriminatory power between MIS-C patients and HC (AUC of 0.7585). Notably, after one week of hospitalization and care, ESM-1 levels decreased, and this reduction was observed also for other inflammatory and pro-thrombotic markers like C-reactive protein, procalcitonin, fibrinogen, D-dimer, and ferritin, suggesting a general recovery trend in MIS-C patients. In fact, we observed that serum ESM-1 levels positively correlated with procalcitonin (PCT) (r = 0.468; p = 0.043). Finally, logistic regression analysis demonstrated an association between endocan levels and cardiac complications like myocarditis. Therefore, this study suggests that ESM-1 is a valuable diagnostic and prognostic biomarker in patients with MIS-C that may help identify those MIS-C patients at higher risk for cardiovascular complications and guide treatment strategies.

The silent predictors: exploring galectin-3 and Irisin’s tale in severe COVID-19

ObjectiveThis study aimed to evaluate the roles of galectin-3 and irisin as biomarkers in predicting severe outcomes in COVID-19 patients.ResultsWe analyzed serum levels of galectin-3 and irisin in 59 patients with severe COVID-19 and 30 healthy controls. Elevated galectin-3 levels were associated with increased risks of mortality, need for intensive care, and severe acute respiratory distress syndrome. The optimal cut-off value for galectin-3 was 13.47 ng/ml, with a sensitivity of 72.7% and specificity of 76.6%. Irisin levels did not differ significantly between survivors and non-survivors at admission or on the 3rd day post-admission, but approached significance on the 7th day. These findings suggest that galectin-3 could be a valuable prognostic biomarker for severe COVID-19 outcomes, while irisin’s role remains to be clarified in further studies.

Pre-treatment of hyponatremia as a biomarker for poor immune prognosis in advanced or metastatic gastric cancer: A retrospective case analysis

ABSTRACT Hyponatremia, a prevalent electrolyte imbalance among tumor patients, has often been overlooked regarding its prognostic significance for immunotherapy. In this study, we delved into the prognostic ramifications of hyponatremia in advanced gastric cancer (AGC) patients undergoing immunotherapy. Enrolling AGC patients diagnosed between December 2014 and May 2021, we extracted pertinent data from electronic medical records, with a median follow-up of 35.8 months. Kaplan–Meier curves illuminated patients’ progression-free survival (PFS) and overall survival (OS), while survival disparities were tested using the Mantel–Haenszel log rank test. COX and logistic regressions were employed to scrutinize the correlation between serum sodium levels and prognosis in 268 AGC patients, both at baseline and during treatment. Notably, patients with hyponatremia exhibited shorter PFS (4.7 vs 2.1 months, p = .001*) and OS (12.5 vs 3.9 months, p < .001*). Serum sodium emerged as an independent prognostic factor for both PFS (HR = 1.773; 95% CI 1.067–2.945; p = .001*) and OS (HR = 1.773; 95% CI 1.067–2.945; p = .003*). Subgroup analysis revealed that AGC patients with hyponatremia derived no benefit from immunotherapy in terms of PFS and OS. Strikingly, a decrease in serum sodium during immunotherapy was associated with early relapse and mortality. Based on these findings, we hypothesize that hyponatremia portends poor prognostic outcomes in AGC patients treated with immunotherapy and may serve as a valuable prognostic biomarker. However, further large-scale prospective studies are warranted to validate these observations.

The Influence of Microbiota on Breast Cancer: A Review

Breast cancer remains one of the leading causes of death among women worldwide, and recent research highlights its growing connection to alterations in the microbiota. This review delves into the intricate relationship between microbiotas and breast cancer, exploring its presence in healthy breast tissue, its changes during cancer progression, and its considerable impact on both the tumor microenvironment (TME) and the tumor immune microenvironment (TIME). We extensively analyze how the microbiota influences cancer growth, invasion, metastasis, resistance to drugs, and the evasion of the immune system, with a special focus on its effects on the TIME. Furthermore, we investigate distinct microbial profiles associated with the four primary molecular subtypes of breast cancer, examining how the microbiota in tumor tissues compares with that in adjacent normal tissues. Emerging studies suggest that microbiotas could serve as valuable diagnostic and prognostic biomarkers, as well as targets for therapy. This review emphasizes the urgent need for further research to improve strategies for breast cancer prevention, diagnosis, and treatment. By offering a detailed examination of the microbiota’s critical role in breast cancer, this review aims to foster the development of novel microbiota-based approaches for managing the disease.

Serum Prealbumin Levels and Risks of Adverse Clinical Outcomes After Ischemic Stroke.

Prealbumin is a symbol of protein nutrition and is involved in anti-inflammatory and neuron regeneration, but its association with the prognosis of ischemic stroke remains unclear. We aimed to prospectively explore the associations between serum prealbumin levels and adverse clinical outcomes after ischemic stroke in a large-scale cohort study. We measured serum prealbumin levels among 6609 ischemic stroke patients admitted at Minhang hospital. The primary outcome was composite of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3 months after stroke onset, and secondary outcomes included death and the ordered 7-level categorical score of mRS. During 3 months of follow-up, a total of 2118 patients developed the primary outcome. After multivariable adjustment, high prealbumin levels were associated with a decreased risk of primary outcome (odds ratio, 0.71; 95% CI, 0.59-0.85; P trend< 0.0001) when 2 extreme quartiles were compared. Each unit increase of log-transformed prealbumin was associated with a 42% (95% CI, 28-53%) decreased risk of primary outcome. There was a better shift in the distribution of mRS score at 3 months with higher quartiles of serum prealbumin in ischemic stroke patients (P trend< 0.0001). Multivariable-adjusted spline regression model showed a linear relationship between prealbumin and the risk of primary outcome (P for linearity = 0.0036). High serum prealbumin level was independently associated with decreased risks of adverse clinical outcomes among ischemic stroke patients. Our findings suggested that prealbumin may be a valuable prognostic biomarker and indicated the importance of keeping nourished in the daily life.

Evaluation of serum fibronectin levels and fibronectin gene polymorphism in patients receiving intravesical BCG therapy for non-muscle invasive bladder cancer and its prognostic value

BackgroundBladder cancer continues to be a significant health issue, leading to ongoing research into novel biomarkers and treatment strategies. This study aims to evaluate the potential of serum fibronectin levels and fibronectin gene polymorphisms as biomarkers for predicting the recurrence and treatment response in patients with NMIBC undergoing intravesical BCG therapy.MethodsBetween June 2022 and December 2022, data of 73 patients who applied to the Mersin University Urology Clinic due to NMIBC and were followed and treated in our clinic, receiving intravesical BCG treatment, when necessary, as well as 56 individuals without any malignancy, were prospectively examined. Serum fibronectin levels were measured using the enzyme-linked immunosorbent assay method. PCR testing was applied for the fibronectin gene RS10202709 and RS 35,343,655 gene polymorphisms by using Real-Time PCR.ResultsThe mean serum fibronectin level in the patient group was 76.794 ± 66.998ng/ml. Simultaneously, it was 50.486 ± 25.156ng/ml in the control group, and these differences in serum fibronectin levels were statistically significant(p = 0.003). Out of the 73 patients included in the study, recurrence of bladder cancer was observed in 53 of them. They were divided into two groups based on the recurrence times: early recurrence and late recurrence. The mean fibronectin level in the early recurrence group was 102 ± 86.1 ng/ml, while it was 44.7 ± 11.8 ng/ml in the late recurrence group. Emphasize the significance of the higher fibronectin levels in the early recurrence group by stating, patients with early recurrence exhibited significantly higher serum fibronectin levels compared to those with late recurrence (p < 0.001), suggesting a potential role for fibronectin as a prognostic biomarker.ConclusionsThe statistically higher concentrations of serum fibronectin levels in patients with bladder cancer observed in our study are a noteworthy finding. These findings suggest that serum fibronectin levels could serve as a valuable prognostic biomarker for early recurrence in NMIBC patients, although their predictive value for BCG treatment response remains limited.

Prognostic value of red blood cell distribution width-to-albumin ratio in ICU patients with coronary heart disease and diabetes mellitus.

The red blood cell distribution width (RDW)-to-albumin ratio (RAR) has emerged as a potentially valuable prognostic indicator in diverse medical conditions. However, the prognostic significance of RAR in intensive care unit (ICU) patients with coronary heart disease (CHD) and diabetes mellitus (DM) remains uncertain and requires further investigation. This study aims to investigate the prognostic significance of RAR in ICU patients with coexisting CHD and DM through a retrospective cohort analysis using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (version 2.2). The study population included patients aged 18 years or older who were diagnosed with both CHD and DM. The primary endpoint was 1-year mortality, and the secondary endpoints included 30-day mortality, 90-day mortality, hospital length of stay (LOS), and ICU LOS. A total of 3416 patients, of whom 64.64% were male, were included in the study. The 30-day mortality, 90-day mortality, and 1-year mortality were 7.08%, 7.44%, and 7.49%, respectively. After adjusting for confounding factors, multivariate Cox proportional risk analysis demonstrated that high RAR levels were associated with an increased risk of 30-day mortality (HR, 1.53 [95% CI 1.17-2.07], P = 0.006), 90-day mortality (HR, 1.58 [95% CI 1.17-2.13], P = 0.003), and 1-year mortality (HR, 1.58 [95% CI 1.17-2.13], P = 0.003). Furthermore, the restricted cubic spline (RCS) model indicated a linear relationship between RAR and 1-year mortality. The results suggest that RAR holds potential as a valuable prognostic biomarker in ICU patients with both CHD and DM. Elevated RAR levels were found to be significantly associated with increased mortality during hospitalization, facilitating the identification of individuals at higher risk of adverse outcomes. These findings underscore the importance of incorporating RAR into risk stratification and overall management strategies for ICU patients with coexisting CHD and DM.

Expression profiling of circulating lncRNA GIAT4RA, lncRNA AATBC, lncRNA Sirt1-AS, and SMARCB1 in lung cancer patients

Long noncoding RNAs (lncRNAs) are crucial regulators of biological processes such as transcription interference and activation, chromatin remodeling, and mRNA translation. Uncontrolled gene expression could result from various epigenetic modifiers, like lncRNAs. So, this study aimed to evaluate the expression profiles of lncRNA GIAT4RA, lncRNA AATBC, lncRNA Sirt1-AS, and SMARCB1 in lung cancer. The current study included lung cancer patients (n = 50), patients with chronic inflammatory diseases (n = 30), and healthy volunteers (n = 20). The expression of blood genes and the concentration of serum neuron-specific enolase were determined by real-time PCR and electrochemiluminescence immunoassay, respectively. The receiver operating characteristic and Kaplan-Meier analyses assess the sensitivity of genes as diagnostic and prognostic biomarkers, respectively. LncRNA GIAT4RA and lncRNA AATBC were upregulated, while lncRNA Sirt1-AS was significantly downregulated in all patients compared to the control group. SMARCB1 expression was significantly downregulated in chronic inflammatory patients, while in those with lung cancer, it showed an insignificant difference. The expression of lncRNA GIAT4RA and lncRNA AATBC was significantly related to the stage of lung cancer. The survival analyses showed that lower lncRNA Sirt1-AS was linked to lung cancer patients’ poorer disease-free survival and overall survival. Differences in lncRNA GIAT4RA, lncRNA AATBC, and lncRNA Sirt1-AS expression were detected in all patients. The consequent abnormal expression of lncRNAs could be crucial in lung cancer development. LncRNA GIAT4RA, lncRNA AATBC, and lncRNA Sirt1-AS may be utilized as promising diagnostic biomarkers. LncRNA AATBC, lncRNA Sirt1-AS, and SMARCB1 may be valuable prognostic biomarkers for lung cancer.

Preoperative Posterior Stromal Ripples as Predictive Biomarkers of Visual Recovery After DMEK.

To investigate the role of preoperative posterior stromal ripples (pre-PSR) on visual acuity recovery after Descemet membrane endothelial keratoplasty (DMEK). This is a comparative case series retrospectively analyzing patients who underwent DMEK. Electronic records and imaging of DMEK patients were reviewed. The last preoperative and first postoperative available anterior segment optical coherence tomography scans for each eye were analyzed for the presence of pre-PSR. The difference in longitudinal trends of visual acuity recovery after DMEK was assessed in eyes with and without pre-PSR. The frequency of rebubbling and measures of proportional relative risk of rebubbling were analyzed according to the presence of preoperative and postoperative PSR. A total of 66 patients (71 eyes) were included. Pre-PSR were associated with lower preoperative visual acuity [0.6 (0.5) vs. 0.9 (0.6) LogMAR, P = 0.02] and higher central corneal thickness [613 (73.8) vs. 715.7 (129.6) micron, P < 0.001]. Eyes with pre-PSR had a slower visual recovery up to 3.5 months after surgery compared to eyes without pre-PSR and achieved lower final visual acuity [0.1 (0.2) vs. 0.3 (0.3) LogMAR, P = 0.02]. Cox proportional hazard ratios showed that postoperative PSR were associated with a greater risk of rebubbling [hazard ratio (95% CI), 7.1 (1.3, 39.5), P = 0.02] while pre-PSR were not. The presence of pre-PSR is associated with slower visual recovery and lower final visual acuity after DMEK while postoperative PSR confer a higher risk of rebubbling. PSR represent a valuable prognostic biomarker both before and after DMEK.

Smartphone-based lateral flow immunoassay for sensitive determination of lactate dehydrogenase at the point of care

Lactate dehydrogenase (LDH), a prevalent enzyme involved in anaerobic glycolysis, is released into body fluids following cell damage and has long been a general marker of tissue injury. However, due to its lack of selectivity and the advent of more accurate biomarkers, the clinical utility of LDH has been largely limited to confirming hemolysis. LDH has been recognized as a valuable prognostic biomarker for various cancers, making its monitoring crucial during cancer management. Traditional LDH methods include spectrophotometric analysis of NADH at 340 nm, native electrophoresis, or enzyme-linked immunosorbent assay. This study presents the first lateral flow immunoassay (LFIA) for the smartphone-based quantification of serum LDH levels at the point of care. Highly-affinity and specific antibodies have been produced, with 5 nM equilibrium dissociation constant and no cross-reactivity with human serum albumin and human immunoglobulin G. Utilizing carbon nanoparticles as signal transducers significantly enhanced the quantification limit 55-fold, compared to the conventional gold nanoparticles-based LFIA, achieving a quantification limit of 1.5 ng mL−1. The developed assay demonstrated a mean recovery rate of 115 ± 21 % when evaluating LDH-spiked serum samples. This method can be an interesting home-testing tool for monitoring cancer progression or therapy effectiveness.

Inferring Characteristics of the Tumor Immune Microenvironment of Patients with HNSCC from Single-Cell Transcriptomics of Peripheral Blood.

Our work offers a new and promising paradigm in liquid biopsies to unlock the power of blood single-cell transcriptomics in cancer immunotherapy.

Clinicopathological and prognostic value of tertiary lymphoid structures in lung cancer: a meta-analysis.

The purpose of this meta-analysis was to examine the clinicopathological and prognostic significance of tertiary lymphocytic infiltrates in lung cancer. A systematic search was performed in many databases, including PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wangfangdate, and CBM, up until January 2024. We calculated the hazard ratio (HR), odds ratios (OR), and confidence interval (CI), and accomplished this meta-analysis with Stata 15 software. 14 studies, including 3101 patients, were subjected to analysis. High TLS detection was associated with a longer OS (HR = 0.545, 95% CI: 0.359-0.827, p = 0.004), DFS (HR = 0.431, 95% CI: 0.350-0.531, p < 0.001), and RFS (HR = 0.430, 95% CI: 0.325-0.569, p < 0.001). Meanwhile, it was observed that a higher detection of TLS was significantly correlated with the administration of adjuvant chemotherapy (OR = 1.505, 95% CI: 1.017-2.225, p = 0.041). Not only that, but there was a higher occurrence of significantly elevated TLS detection in the early N stages (N = 0) compared to the advanced N stages (N = 1, 2, and 3) (OR = 1.604, 95% CI: 1.021-2.521, p = 0.04). Elevated detection of TLS has been observed to be correlated with extended OS, DFS, and RFS in cases of lung cancer. This finding suggests that TLS could potentially serve as a valuable prognostic biomarker for lung cancer.

The expression and clinical significance of ARHGAP25 in osteosarcoma based on bioinformatics analysis

ARHGAP25, a member of the ARHGAP family, encodes a negative regulator of Rho-GTPase that is important for actin remodeling, cell polarity, and cell migration. ARHGAP25 is down-regulated in a variety of solid tumors and promotes cancer cell growth, migration, and invasion. However, nothing is understood about ARHGAP25’s biological function in osteosarcoma. This work used qPCR and WB to confirm the expression of ARHGAP25 in osteosarcoma following the initial analysis of its expression in pan-cancer. For GO and KEGG analysis, we have chosen 300 genes from the TARGET osteosarcoma data that had the strongest positive correlation with ARHGAP25, and we created nomogram and calibration charts. We simultaneously overexpressed ARHGAP25 in osteosarcoma cells to examine its impact on apoptosis and proliferation. By using MSP, we determined their methylation status in osteosarcoma cells and normal bone cells. We observed that ARHGAP25 was significantly downregulated in a range of malignancies, including osteosarcoma, and was associated with poor patient outcomes. The decrease of ARHGAP25 expression in osteosarcoma is related to DNA methylation. Overexpression of ARHGAP25 induced apoptosis and inhibited the proliferation of osteosarcoma cells in vitro. In addition, ARHGAP25 is also associated with immune-related pathways in osteosarcoma. These findings suggest that ARHGAP25 is a valuable prognostic biomarker in osteosarcoma patients.

Comprehensive pan-cancer analysis of ZNF337 as a potential diagnostic, immunological, and prognostic biomarker

BackgroundZinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated.MethodsIn this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients.ResultsThe pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects.ConclusionsZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC.