Unfavorable Prognostic Marker Research Articles

ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells

Cholangiocarcinoma (CCA) is a bile duct malignancy. Our previous comprehensive analysis showed that ferroptosis-related genes can stratify CCA patients into low-risk and high-risk groups based on survival time. Here, we explored the role of ferroptosis in CCA by analyzing mRNA expression in CCA patients from public databases. We identified acyl-CoA synthetase long chain family member 3 (ACSL3) as a potential ferroptosis suppressor in high-risk CCA patients. Using a panel of CCA cell lines, we confirmed ACSL3 upregulation in CCA cell lines associated with high-risk CCA, correlating this with resistance to the ferroptosis inducer RSL3. Lipidomic analysis revealed increased monounsaturated fatty acid (MUFA)-containing phospholipids in resistant cell lines. ACSL3 silencing sensitized these cells to RSL3. Resistance to ferroptosis was also dependent on exogenous MUFAs and was enhanced by lipid droplet biogenesis inhibition. These findings highlight ACSL3 as a promising target for therapeutic strategies aimed at overcoming ferroptosis resistance in CCA.

The role of malnutrition and dependence on outside help in hospitalized elderly patients with decompensated heart failure

Abstract Introduction Despite recent achievement in the diagnosis and treatment of heart failure, the prognosis for disease remains unfavorable especially in elderly patients. It has been recently actively proposed to introduce a comprehensive geriatric assessment to determine the group of adverse outcome and frailty, however the assessment of geriatric syndromes in acute decompensated heart failure (ADHF) among hospitalized patients is poor. Aim To assess the prognostic role of malnutrition and dependence on outside help in hospitalized elderly patients with ADHF. Materials and methods The study included 60 patients over 75 years old who were hospitalized for ADHF. The median [IQR] age was 83.0 [77.0-87.0] years, 41.7% (n=25) were men. The preserved left ventricular ejection fraction (LVEF) prevailed – 51.2% (n=22), moderately reduced and low LVEF – 23.3% (n=10) and 25.6% (n=11), respectively. Total/severe dependence on outside help was determined with Barthel Index of ≤60 points, malnutrition – with a Mini Nutritional Assessment Scale of <17 points, sarcopenia with SARC-F ≥4 points. At discharge, all patients underwent bioimpedance analysis of body composition (BIA). The primary endpoint was hospital mortality. Results 48.3% (n=29) of hospitalized elderly patients with ADHF had total/severe dependence on outside help. This group of patients had a higher risk of malnutrition (OP 2.01, 95% CI 1.49-2.83, p=0.04) and sarcopenia (OP 8.25, 95% CI 1.55-44.02, p=0.01). Elderly patients with ADHF and malnutrition had a more severe functional class (NYHA III-IV) than patients without malnutrition (97.1% vs. 66.7%, respectively, p=0.02). There were no differences in ADHF phenotypes depending on the presence of malnutrition. The ability to self-serve according to Barthel Index has positively correlated with the BIA Index (r=0.483, p=0.04). The risk of sarcopenia on the SARC-F scale has negatively correlated with fat, lean and active cell mass according to BIA (r=-0.538, r=-0.599 and r=-0.532, respectively, p<0.05). Elderly patients with ADHF and a combination of total/severe dependence on outside help and malnutrition (27.9%, n=12) had higher inflammation level (neutrophil-lymphocytic index 5.6 [2.6-7.7] vs. 3.9 [2.0-6.0], p=0.03, respectively) and the need for longer intravenous diuretic therapy (OP 4.38, 95% CI 1.21-15.81, p=0.03) compared with patients without these disorders (72.1%, n=31), The primary endpoint was reached by 4 patients, in 100% of cases there was a combination of total/severe dependence on outside help and malnutrition. Conclusion The combination of total/severe dependence on outside help and malnutrition is an unfavorable prognostic marker of hospital mortality in hospitalized elderly patients with ADHF. A comprehensive geriatric assessment and determination of body composition can identify a risk group for an adverse outcome.

Targeting sphingolipid metabolism in chronic lymphocytic leukemia

Elevated levels of circulating C16:0 glucosylceramides (GluCer) and increased mRNA expression of UDP-glucose ceramide glycosyltransferase (UGCG), the enzyme responsible for converting ceramides (Cer) to GluCer, represent unfavorable prognostic markers in chronic lymphocytic leukemia (CLL) patients. To evaluate the therapeutic potential of inhibiting GluCer synthesis, we genetically repressed the UGCG pathway using in vitro models of leukemic B cells, in addition to UGCG pharmacological inhibition with approved drugs such as eliglustat and ibiglustat, both individually and in combination with ibrutinib, assessed in cell models and primary CLL patient cells. Cell viability, apoptosis, and proliferation were evaluated in vitro, and survival and apoptosis were examined ex vivo. UGCG inhibition efficacy was confirmed by quantifying intracellular sphingolipid levels through targeted lipidomics using mass spectrometry. Other inhibitors of sphingolipid biosynthesis pathways were similarly assessed. Blocking UGCG significantly decreased cell viability and proliferation, highlighting the oncogenic role of UGCG in CLL. The efficient inhibition of UGCG was confirmed by a significant reduction in GluCer intracellular levels. The combination of UGCG inhibitors with ibrutinib demonstrated synergistic effect. Inhibitors that target alternative pathways within sphingolipid metabolism, like sphingosine kinases inhibitor SKI-II, also demonstrated promising therapeutic effects both alone and when used in combination with ibrutinib, reinforcing the oncogenic impact of sphingolipids in CLL cells. Targeting sphingolipid metabolism, especially the UGCG pathway, represents a promising therapeutic strategy and as a combination therapy for potential treatment of CLL patients, warranting further investigation.

The Fingerprint of Scalp-EEG in Drug-Resistant Frontal Lobe Epilepsies.

Scalp-EEG incompletely covers the frontal lobe cortex. Underrepresentation of frontobasal or frontomesial structures, fast ictal spreading, and false lateralization impede scalp-EEG interpretation. Hence, we investigated the significance of scalp-EEG in the presurgical workup of frontal lobe epilepsy. Using descriptive statistical methods and Pearson chi-squared test for group comparisons, we retrospectively investigated postsurgical outcome, interictal epileptiform discharges (iiEDs), and electrographic seizure patterns on scalp-EEG in 81 consecutive patients undergoing resective epilepsy surgery within the margins of the frontal lobe. Postoperatively, patients with frontopolar iiEDs (n = 7) or concordant frontopolar iiED focus and seizure-onset (n = 2) were seizure free (n = 7/7, Engel Ia). MRI-positive patients with frontopolar iiEDs or frontopolar seizure-onset (n = 1/8 Engel Id, n = 7/8 Engel Ia) underwent surgery without stereo-EEG. Thirteen of 16 patients with frontolateral (n = 8/10, Engel Ia), or left frontobasal (n = 5/6, Engel Ia) seizure-onset undergoing further stereo-EEG, were seizure-free postoperatively. Seizure-onset prevalent over one electrode (n = 37/44 Engel I, p = 0.02), fast activity (FA)/flattening at seizure-onset (n = 29/33 Engel I, p = 0.02), FA/flattening during the seizure (n = 38/46 Engel I, p = 0.05), or focal rhythmic sharp-/spike-/polyspike-and-slow waves during the seizure (n = 24/31, Engel Ia, p = 0.05) were favorable prognostic markers. Interictal polyspike waves (p = 0.006 for Engel Ia) and interictal paroxysmal FA (p = 0.02 for Engel I) were unfavorable prognostic markers. Frontopolar scalp-EEG findings serve as biomarkers for predicting favorable surgical outcome in lesional frontal lobe epilepsy. Consequently, careful analysis of scalp-EEG assists in bypassing stereo-EEG in these patients.

Hyper-methylation and DNMT3A mediated LTC4S downregulation promoted lung adenocarcinoma tumorigenesis via mTORC1 signaling pathway

BackgroundLung adenocarcinoma is a malignancy characterized by high mortality rates and unfavorable prognosis. However, the role of Leukotriene C4 Synthase (LTC4S) in lung cancer remains uninvestigated. MethodsThe expression and prognostic value of LTC4S in LUAD were analyzed using the GEPIA online database. Subsequently, the function of LTC4S in lung cancer cells was examined through gain-of function experiments, using assays to evaluate tumor malignant behavior. Subcutaneous xenograft experiments in vivo was used for investigating the functions of LTC4S. Then, tumor hallmark pathways were analyzed by GSEA. Western blot assay was used to validate the impact of LTC4S on mTORC1 pathway. Finally, the correlation of mRNA and methylation of LTC4S were analyzed by cBioPortal. qRT-PCR, ChIP-qPCR and ChIP-Atlas were used to verify the regulation factors of LTC4S low expression in LUAD cells. ResultsLTC4S presented significant decreased expression and favorable prognostic significance in LUAD. LTC4S was correlated with clinical stages in LUAD, which showed decreased expression gradually and significantly along with TNM stages. LTC4S-co-expressed genes were closely related to Ras signaling pathway, and MAPK signaling pathway. Overexpression of LTC4S inhibited cancer malignant phenotype and tumor growth in vitro and vivo. GSEA analysis and Western blot assay suggested low expression of LTC4S activated mTORC1 signaling pathway in LUAD. Moreover, the DNA methylation level of LTC4S in LUAD tissue was markedly elevated compared to normal tissue. The hypermethylation of the LTC4S promoter by DNMT3A leads to the decreased expression of LTC4S in LUAD. ConclusionsIn conclusion, low expression of LTC4S serves as an unfavorable prognostic marker and the critical function of LTC4S in controlling the progression of LUAD. This highlights the promise for exploring the clinical benefits of manipulating LTC4S in LUAD targeted therapies.

STUDY OF HIF-1Α-SIGNALING PATHWAY COMPONENTS IN PLASMA OF PATIENTS WITH COVID-19 INFECTION OF DIFFERENT DEGREES OF SEVERITY

Introduction. Recent work demonstrates that HIF-1α and NOS isoforms are detectable in plasma, representing their potential practical relevance as biomarkers. At the same time, data on the stability of these proteins in plasma are contradictory. Aim of the study. To investigate the amount of HIF-1α and iNOS in plasma of patients with COVID-19 infection of different severity to assess the possi-bilities of adaptation to hypoxia. Material and methods. The pilot study involved 50 patients divided into three groups: 1) 17 patients with moderate severity of the disease; 2) 17 pa-tients in severe condition; 4) 16 patients with extremely severe course of the disease. The amounts of HIF-1α and iNOS were determined by competi-tive ELISA. Results. Patients with extremely severe course of COVID-19 infection showed lower levels of HIF-1α and blood saturation compared to the moderate and severe course groups. The iNOS levels were significantly lower in the extremely severe course group compared to patients with moderate disease severity. When patients were evaluated according to the degree of lung damage based on CT scans, reduced HIF-1α levels were identified in the CT-3-4 group compared to the CT-0-1 (p = 0.0006) and CT-2 (p = 0.0031) groups. Conclusions. Decreased levels of HIF-1α and iNOS in extremely critically ill patients may serve as an unfavorable prognostic marker

Low expression of the <i>ST6GAL2</i> and <i>CD248</i> genes as an unfavorable prognostic marker of oral squamous cell carcinoma

Introduction. Squamous cell carcinoma (SCC) of the oral cavity is an aggressive and rapidly progressing disease. The tendency to progression of the tumor process is due to the clinical and pathological characteristics of the patient and the biological characteristics of the tumor. molecular and genetic disorders related with transcriptome level play an important role in tumor progression, which can be used in predicting the outcome of the disease. Aim. To identify markers for assessing the risk of the SCC progression. Materials and methods. Based on the data of the Cancer genome Atlas database, a bioinformatic search for genes associated with the progression of SCC was performed (11 genes were selected). Then we performed a retrospective analysis of clinical data and histological material from 38 patients with SCC treated at the Scientific Research Institute of Oncology of the Tomsk National Research medical Center of the Russian Academy of Sciences from 2018 to 2021. Fixed samples of tumor tissue were examined. The level of gene expression was determined by real-time quantitative polymerase chain reaction. Results. It was shown that decrease in the ST6GAL2 matrix RNA level is associated with presence of lymphogenic metastases and decrease in the CD248 matrix RNA level is associated with the occurrence of relapses. Conclusion. Expression level of the ST6GAL2 and CD248 genes can be used as predictors of an unfavorable prognosis of SCC.

Abstract 2550: Investigating glutathione peroxidases as potential prognostic factors in uterine corpus endometrial cancer

Abstract Introduction: Uterine corpus endometrial cancer (UCEC) is one of the deadliest women’s reproductive cancers in the United States, and mortality rates have not improved in the last 30 years due to poor prognostic methodologies. Altered expression patterns of Glutathione Peroxidases (GPX1-8) have been connected to the outcome of many cancers. Still, GPX expression patterns and their use as prognostic biomarkers in UCEC have yet to be explored. This project aimed to evaluate the potential utility of GPX1-8 as prognostic biomarkers for UCEC. Methods: To identify GPX1-8 expression alterations in UCEC tumors, the UCEC tissue samples (n=543) from the Cancer Genome Atlas Database (TCGA) dataset were analyzed using the University of Alabama at Birmingham Cancer Data Analysis portal (UALCAN) software to statistically compare mRNA levels between UCEC tumor samples and non-tumorigenic uterine tissue. To determine the impacts of GPX1-8 expression on overall survival (OS) and relapse-free survival (RFS), the UCEC TCGA dataset was analyzed using the pan-cancer RNA seq platform using Kaplan-Meier Plotter (KM plotter). The patient cohort was split into groups according to high GPX expression status and low GPX expression status using the trichotomization function in KM plotter. Hazard ratio (HR), 95% confidence interval (95% CI), and log-rank P value were calculated using the KM plotter platform. Results: GPX1, GPX2, GPX4, GPX7, and GPX8 were differentially expressed in UCEC tumor tissue compared to non-cancerous uterine tissue. However, unfavorable OS in patients associated with low GPX4 expression in UCEC tumor samples (P=0.0043, HR=0.39, 95% CI=0.2-0.76) only. Unfavorable RFS in UCEC patients only correlated with low GPX1 expression (P=0.019, HR=0.43, 95% CI=0.21-0.89) or high GPX6 expression (P=0.0032, HR=2.37, 95% CI=1.31-4.27) in UCEC tumor samples. Conclusion: Low GPX1 and GPX4 expression and high GPX6 expression may be novel unfavorable UCEC prognostic markers. Citation Format: Alexis Dukesherer, Calli A. Davison-Versagli. Investigating glutathione peroxidases as potential prognostic factors in uterine corpus endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2550.

Papillary Thyroid Cancer Trends in the Wake of the COVID-19 Pandemic: Is There a Shift toward a More Aggressive Entity?

Globally, the incidence of papillary thyroid cancer (PTC) has been increasing over the last few decades and it has become the second most common cancer in women in the UAE. There is some evidence to suggest that COVID-19 infection might be directly linked to the development of aggressive variants of PTC. The primary goal of this study was to compare the clinical and pathologic characteristics of thyroid cancer patients treated at the largest endocrine surgery center in Abu Dhabi before and after the COVID-19 pandemic outbreak. This retrospective cohort analysis included patients who underwent elective thyroid surgery at Burjeel Hospital between January 2018 and December 2022. Patients were divided into two groups based on when the COVID-19 outbreak started: group one, comprising patients who had surgery between January 2018 and December 2019 (the "pre-pandemic group"), and group two, comprising patients who had surgery between January 2021 and December 2022 (the "post-pandemic group"). In addition to demographic data, clinicopathological factors, such as aggressive cell type, multifocality, tumor size and location, laterality, lympho-vascular invasion, and extrathyroidal extension, were assessed. We utilized the t-paired test for parametric variables and the Chi-square test for the cross-table analysis. During the study, 1141 people had thyroid surgery, with an annual average of 285 procedures. PTC cases recorded in the final histopathological samples rose from 111 in the pre-pandemic era to 182 in the post-pandemic era. Neither the female-to-male gender ratio, which was 90:21 in the pre-pandemic group and 142:40 in the post-pandemic group (p = 0.532), nor the median age, which was 39.1 and 40.1 years, respectively, varied significantly between the two groups. However, there was a significant increase between pre-pandemic and post-pandemic in the aggressive PTC variants (3% vs. 11.5%, p = 0.001), increased poor prognostic factors such as bilateral multifocality (10.8% vs. 32.4%, p = 0.000), as well as increased capsule-vascular tumor invasion (19.8% vs. 27%); on the other hand, the size of the single foci was 17 mm in the pre-pandemic group compared to 13 mm in the post-pandemic group (p = 0.001). A significant rise in unfavorable prognostic markers and aggressive subtypes of PTC was seen post-pandemic in thyroidectomy patients operated on at a leading endocrine surgery center in the United Arab Emirates.

The ISTH DIC-score predicts early mortality in patients with non-promyelocitic acute myeloid leukemia

Coagulation disorders frequently complicate the clinical course of acute myeloid leukemia (AML) patients. This study examined the frequency and prognostic significance, with regards of early mortality, of the presence of overt disseminated intravascular coagulation (DIC) at AML diagnosis and its correlation with clinical and biological characteristics.A retrospective analysis of 351 newly diagnosed non-promyelocytic AML patients was conducted, utilizing the 2018 ISTH DIC-Score criteria to evaluate the presence of overt DIC at AML onset. The study cohort had a median age of 65 years with a predominance of male gender (59 %). Overt DIC was present in 21 % of cases and was associated with advanced age, comorbidities, poor performance status, hyperleukocytosis, LDH levels, NPM1 mutations, expression of CD33 and CD4, and lack of expression of CD34. With a median follow-up of 72 months (3–147 months), the 6-year overall survival (OS) was 17.4 %, with patients having overt DIC showing significantly poorer outcomes (7.2 % compared to 20.3 % of those without DIC, p < 0.001). Patients with overt DIC showed markedly high early mortality rates at 30 (42.5 % vs 8 %), 60 (49.3 % vs 16.9 %), and 120 days (64.4 % vs 25.6 %) from disease onset. In multivariate analysis overt DIC retained its independent prognostic value for early mortality.In conclusion, the prevalence and clinical relevance of DIC in non-promyelocytic AML is not negligible, underlining its potential as an unfavorable prognostic marker. In newly diagnosed patients with AML, early recognition and measure to counteract coagulation disturbances might help mitigate the elevated mortality risk associated with DIC.

DPM2 serve as novel oncogene and prognostic marker transactivated by ESR1 in breast cancer.

Breast cancer (BRCA) is the most common malignancies worldwide with increasing rate. Dolichol phosphate mannose synthase (DPMS) is a critical mannosyltransferase involved in the posttranslational modification of proteins. At present, there is limited knowledge regarding the function of DPMS in breast cancer. In this study, silica analysis in multiple datasets found that dolichyl-phosphate mannosyltransferase subunit 2 (DPM2) is an unfavorable prognostic marker, suggesting its oncogenic role. Cell counting kit-8 and apoptosis assays show that DPM2-silenced cancer cells exhibit decreased growth potential and enhanced cell death rate. Further, transwell and wound healing assays show reduced invasion and migration capabilities in DPM2 knockdown groups, xenograft nude mice model demonstrated smaller tumor volume in DPM2 silenced BC cells. Then, the underlying downstream mechanism of DPM2 in BC was predicted and analyzed, highlighting classical tumorigenic pathways like JAK/STAT signaling pathway and oxidative phosphorylation activated in the cancer group. Finally, ChIP-seq analysis, expression correlation analysis, inhibitor treatment, and dual luciferase assays show that DPM2 is transcriptionally activated by estrogen receptor1 (ESR1). The results show that high expression of DPM2 mRNA is significantly correlated with shorter overall survival (OS) and disease-free survival (DFS) in breast cancer patients, and in vitro knockdown of DPM2 can significantly inhibit the malignant phenotypes of cells, including proliferation, invasion, migration, and apoptosis. These results suggest that DPM2 may play an important role in breast cancer. Altogether, we first uncovered the tumorigenic and prognostic role of DPM2 in breast cancer, cellular assays, and bioinformatics analysis highlighted DPM2 as oncogene via inhibited cancer-related signaling pathways in breast cancer. Besides, DPM2 is transcriptionally activated by ESR1, the signaling axis of ESR1/DPM2 provides a new strategy for BC-targeted therapy.

Clinical and prognostic significance of CD27 and CD44 expression patterns in Egyptian pediatric patients with B-precursor acute lymphoblastic leukemia

IntroductionThe expression pattern of CD27 and CD44 was found to correlate with the differentiation stages of B cell precursors, which were known to be involved in a variety of immunological responses. Aim of the studyThis study aimed to determine the biological significance of CD27 and CD44 expression in patients with B-precursor acute lymphoblastic leukemia (B-ALL), as well as their association with standard prognostic factors and therapeutic response. Patients and methodsThis case-control study included 60 pediatric patients newly diagnosed with B-ALL and 30 pediatric controls. The patient CD27 and CD44 levels were measured using the Beckman Coulter Navios Flow Cytometer. ResultsMost malignant cells (91.6 %) expressed CD44, but only 50 % of the patients had CD27 expressed. The positive CD 44 expression was associated with unfavorable prognostic markers, including a decrease

Prognostic Potential of Galectin-9 mRNA Expression in Chronic Lymphocytic Leukemia.

Galectin-9 (Gal-9), very poorly characterized in chronic lymphocytic leukemia (CLL), was chosen in our study to examine its potential role as a CLL biomarker. The relation of Gal-9 expression in malignant B-cells and other routinely measured CLL markers, as well as its clinical relevance are poorly understood. Gal-9 mRNA expression was quantified with RT-qPCR in purified CD19+ B-cells of 100 CLL patients and analyzed in the context of existing clinical data. Our results revealed the upregulation of Gal-9 mRNA in CLL cells. High Gal-9 mRNA expression was closely associated with unfavorable prognostic markers. In addition, Gal-9 expression in leukemic cells was significantly elevated in CLL patients who did not respond to the first-line therapy compared to those who did respond. This suggests its potential predictive value. Importantly, Gal-9 was an independent predictor for the time to treatment parameters. Thus, we can suggest an adverse role of Gal-9 expression in CLL. Interestingly, it is possible that Gal-9 expression is induced in B-cells by EBV infection, so we determined the patients' EBV status. Our suggestion is that EBV coinfection could worsen prognosis in CLL, partly due to Gal-9 expression upregulation caused by EBV.

Consenso mexicano de linfoma de Hodgkin

Hodgkin's lymphoma is due to the clonal transformation of cells originating from B lymphocytes, generating the pathognomonic binucleate Reed-Sternberg cells. Hodgkin's lymphoma is a B cell disease with a bimodal distribution, with higher incidence in adolescence and the third decade of life, showing a second peak in people over 55 years of age. Classic Hodgkin lymphoma cells routinely undergo gene expression reprogramming, as they lose the expression of most of the typical B-cell genes and acquire the expression of multiple genes that are typical of other types of cells in the immune system. The treatment algorithm will depend on whether it is classic or predominantly lymphocytic HL, if it is early stage with unfavorable prognostic markers or not, the initial management regimen, and whether there is bulky disease, among the most relevant variables.

Analysis of myosin genes in HNSCC and identify MYL1 as a specific poor prognostic biomarker, promotes tumor metastasis and correlates with tumor immune infiltration in HNSCC

Head neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors which ranks the sixth incidence in the world. Although treatments for HNSCC have improved significantly in recent years, its recurrence rate and mortality rate remain high. Myosin genes have been studied in a variety of tumors, however its role in HNSCC has not been elucidated. GSE58911 and GSE30784 gene expression profile analysis were performed to detect significantly dys-regulated myosin genes in HNSCC. The Cancer Genome Atlas (TCGA) HNSCC database was used to verify the dys-regulated myosin genes and study the relationship between these genes and prognosis in HNSCC. The results showed that MYL1, MYL2, MYL3, MYH2, and MYH7 were down-regulated, while MYH10 was up-regulated in patients with HNSCC. Interestingly, MYL1, MYL2, MYH1, MYH2, and MYH7 were shown to be unfavorable prognostic markers in HNSCC. It is also worth noting that MYL1 was a specific unfavorable prognostic biomarker in HNSCC. MYL1, MYL2, MYL3, MYH2, MYH7, and MYH10 promoted CD4 + T cells activation in HNSCC. MYL1 was proved to be down-regulated in HNSCC tissues compared to normal tissues at protein levels. MYL1 overexpression had no effect on proliferation, but significantly promoted migration of Fadu cells. MYL1 increased EGF and EGFR protein expression levels. Moreover, there is a positive correlation between MYL1 expression and Tcm CD8 cells, Tcm CD4 + cells, NK cells, Mast cells, NKT cells, Tfh cells and Treg cells in HNSCC. Overall, MYL1 facilitates tumor metastasis and correlates with tumor immune infiltration in HNSCC and these effects may be associated with the EGF/EGFR pathway.

Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer.

Our understanding of the function of long non-coding RNAs (lncRNAs) in health and disease states has evolved over the past decades due to the many advances in genome research. In the current study, we characterized the lncRNA transcriptome enriched in triple-negative breast cancer (TNBC, n = 42) and estrogen receptor (ER+, n = 42) breast cancer compared to normal breast tissue (n = 56). Given the aggressive nature of TNBC, our data revealed selective enrichment of 57 lncRNAs in TNBC. Among those, AC099850.4 lncRNA was chosen for further investigation where it exhibited elevated expression, which was further confirmed in a second TNBC cohort (n = 360) where its expression correlated with a worse prognosis. Network analysis of AC099850.4high TNBC highlighted enrichment in functional categories indicative of cell cycle activation and mitosis. Ingenuity pathway analysis on the differentially expressed genes in AC099850.4high TNBC revealed the activation of the canonical kinetochore metaphase signaling pathway, pyridoxal 5'-phosphate salvage pathway, and salvage pathways of pyrimidine ribonucleotides. Additionally, upstream regulator analysis predicted the activation of several upstream regulator networks including CKAP2L, FOXM1, RABL6, PCLAF, and MITF, while upstream regulator networks of TP53, NUPR1, TRPS1, and CDKN1A were suppressed. Interestingly, elevated expression of AC099850.4 correlated with worse short-term relapse-free survival (log-rank p = 0.01). Taken together, our data are the first to reveal AC099850.4 as an unfavorable prognostic marker in TNBC, associated with more aggressive clinicopathological features, and suggest its potential utilization as a prognostic biomarker and therapeutic target in TNBC.

Nonspecific intraventricular conduction delay predicts the prognosis of dilated cardiomyopathy

PurposeLeft bundle branch block (LBBB) has been confirmed to be independently associated with adverse outcomes in dilated cardiomyopathy (DCM). However, prognostic data on nonspecific intraventricular conduction delay (NSIVCD) are still limited and conflicting. We aimed to evaluate the prognosis of DCM with NSIVCD.MethodsA total of 548 DCM patients who underwent cardiovascular magnetic resonance imaging (CMR) from January 2016 to December 2017 were consecutively enrolled. The cohort was divided into four groups: 87 with LBBB, 27 with RBBB, 61 with NSIVCD, and 373 without intraventricular conduction delay (IVCD). After a median follow-up of 58 months (interquartile range: 47–65), 123 patients reached the composite endpoints, which included cardiovascular death, heart transplantation, and malignant arrhythmias. The associations between different patterns of IVCD and the outcomes of DCM were analysed by Kaplan‒Meier analysis and Cox proportional hazards regression analysis.ResultsOf 548 DCM patients, there were 398 males (72.6%), and the average age was 46 ± 15 years, ranging from 18 to 76 years. In Kaplan‒Meier analysis, patients with NSIVCD and LBBB showed higher event rates than patients without IVCD, while RBBB patients did not. By multivariate Cox regression analysis, LBBB, NSIVCD, NYHA class, left ventricular ejection fraction (LVEF), indexed left ventricular end-diastolic diameter (LVEDDI), percentage of late gadolinium enhancement mass (LGE%), and global longitudinal strain (GLS) were found to be independently associated with the outcomes of DCM.ConclusionsIn addition to LBBB, NSIVCD was an unfavourable prognostic marker in patients with DCM, independent of LVEDDI, NYHA class, LVEF, LGE%, and GLS.

Pan-cancer analysis from multi-omics data reveals AAMP as an unfavourable prognostic marker

ObjectivesAngio-associated migratory cell protein (AAMP) is a protein that participates in cell migration and is reported to be involved in cancer progression. However, the molecular mechanism of AAMP in pan-cancer is not known.MethodsWe used multi-omics data, such as TIMER, TCGA, GTEx, CPTAC, HPA, and cBioPortal to analyze AAMP expression, and gene alteration in pan-cancer. Univariate Cox regression and Kaplan–Meier were utilized to explore prognostic significance of AAMP expression level. We applied Spearman analysis to investigate the correlation between AAMP and TMB, MSI, immune cell infiltration, immune checkpoints. Moreover, we mainly studied liver hepatocellular carcinoma(LIHC) to explore AAMP expression, clinical significance, and prognosis. Cox regression analysis was used to study independent factor to predict prognosis for AAMP in LIHC. GSEA was utilized to investigate the biological function for AAMP in LIHC.ResultsAAMP was overexpressed in most cancers, and high AAMP expression was associated with worse overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) for LIHC and adrenocortical carcinoma (ACC). Moreover, AAMP had the highest mutation frequency in uterine corpus endometrial carcinoma (UCEC). AAMP was correlated with TMB and MSI in esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), lung squamous cell carcinoma (LUSC), and thyroid carcinoma (THCA). Then, we focus on LIHC to investigate the expression and prognosis of AAMP. AAMP overexpression was related to histological grade and pathological stage in LIHC. Multivariate Cox regression analysis revealed that AAMP overexpression was an independent adverse prognostic marker for LIHC. AAMP expression was correlated with immune cell infiltration and immune checkpoints in LIHC. Function enrichment analysis indicated the participation of AAMP in the cell cycle and DNA replication.ConclusionsAAMP was a latent prognostic indicator for pan-cancer and had high potential as a biomarker for the diagnosis and prognosis of LIHC.

Serum AKR1B10 as an indicator of unfavorable survival of hepatocellular carcinoma.

A large-scale multicenter study validated aldo-keto reductase 1B10 (AKR1B10) as a new serum marker of hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic value of serum AKR1B10 in HCC. 273 naïve HCC patients enrolled for serum AKR1B10 tests were followed up for 2years. Survival and clinical data were collected. Kaplan-Meier survival analysis and log-rank tests were used to estimate correlation of patient survival with serum AKR1B10. Univariate and multivariate COX regression analyses were used to evaluate the prognostic value of serum AKR1B10 level independently or in combination with other clinicopathological factors. α-fetoprotein (AFP) was analyzed in parallel for comparison. Serum AKR1B10 associated with tumor stage (p = 0.012), size (p = 0.004), primary tumor number (p = 0.019), and Child-Pugh classification (p = 0.003). HCC patients with a high level of serum AKR1B10 (≥ 267.9pg/ml) had median survival (MS) of 25months (95% confidence interval [CI] 20.788-29.212) vs. MS of 34months (CI 28.911-39.089) in patients with normal serum AKR1B10 (p < 0.001). Univariate and multivariate COX regression analyses showed that serum AKR1B10 level was an unfavorable prognostic marker of HCC independently (HR 1.830, 95% CI 1.312-2.552; p < 0.001) or in combination with other clinical factors (HR 1.883, 95% CI 1.264-2.806; p = 0.002), such as TNM stage, tumor size and portal invasion. In the same cohort of HCC patients, AFP exhibited prognostic value at a cut-off of 400ng/ml, but not at 20ng/ml and 200ng/ml. Serum AKR1B10 is a new prognostic marker of HCC, better than AFP.

FAM72 family proteins as poor prognostic markers in clear cell renal carcinoma

PurposeThis study aimed to investigate the prognostic significance of the Family with Sequence Similarity 72 member (FAM72) gene family in clear cell renal carcinoma (ccRCC) using a bioinformatic approach. Patients and methodsTo investigate the association between FAM72 and ccRCC, we utilized various databases and analysis tools, including TCGA, GEPIA, Metscape, cBioPortal, and MethSurv. We conducted an analysis of FAM72 expression levels in ccRCC tissues compared to normal kidney tissues and performed univariate and multivariate Cox analysis to determine the relationship between FAM72 expression and patient prognosis. Furthermore, we carried out Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) to identify enriched biological processes associated with FAM72 expression. Additionally, we analyzed immune cell infiltration and the level of methylation in ccRCC patients. Our bioinformatic analysis revealed that FAM72 expression levels were significantly higher in ccRCC tissues than in normal kidney tissues. High expression of FAM72 was associated with poor prognosis in ccRCC patients and was found to be an independent prognostic factor for ccRCC. GO and GSEA analyses indicated that FAM72 was enriched in biological processes related to mitosis, cell cycle, and DNA metabolism. Moreover, we found a significant correlation between FAM72 and immune cell infiltration and the level of methylation in ccRCC patients. ConclusionOur findings suggest that FAM72 could serve as an unfavorable prognostic molecular marker for ccRCC. A comprehensive understanding of FAM72 could provide crucial insights into tumor progression and prognosis.