Potential Prognostic Biomarker Research Articles

Long non-coding RNA LINC00930 targeting miR-6792-3p/ZBTB16 regulates the proliferation and EMT of pancreatic cancer

Emerging evidence suggests the dysregulation of long non-coding RNAs (lncRNAs) involved in pancreatic cancer (PC). However, the function of LINC00930 in PC has not been elaborated. In this study, we found that LINC00930 was significantly down-regulated in PC cell lines and tissues, and associated with tumor size, lymphatic metastasis, TNM stage and poor prognosis. According to the bioinformatics database, the downregulation of LINC00930 was a common event in PC associated with prognosis and EMT. Overexpression of LINC00930 inhibited the aggressive cancer phenotypes including proliferation, metastasis and epithelial-mesenchymal transition (EMT) of PC in vitro and in vivo. Bioinformatics and dual-luciferase reporter assay indicated that miR-6792-3p could directly bind to LINC00930. Additionally, the Zinc finger and BTB domain containing 16 (ZBTB16) was significantly declined in PC, which was predicted to be the downstream gene of miR-6792-3p. MiR-6792-3p mimic rescued the decreased proliferation, metastasis and EMT caused by ZBTB16 in PC cells. The LINC00930/miR-6792-3p/ZBTB16 axis was associated with the malignant progression and process of PC. The relative expression of LINC00930 was negatively correlated with the expression of miR-6792-3p and was closely linked with ZBTB16 levels in PC. LINC00930 might serve as a potential prognostic biomarker and therapeutic target for PC.

Association between leukocyte telomere length and heart failure hospitalization based on the presence of the atrial fibrillation

Abstract Leukocyte telomere length (LTL) is a well-established biomarker linked to cardiovascular disease, with shorter LTL associated with increased severity of heart failure (HF) outcomes. It is also well known that atrial fibrillation (AF) and HF are closely related and often coexist. This study explores the relationship between LTL and hospitalization due to HF, considering both AF and non-AF patients within the UK Biobank cohort. Retrospective analysis of the UK Biobank dataset (n=451,552, mean age 57.0±8.1 years, 45.8% male) excluded individuals with pre-existing HF (n=12,162) and extreme/no LTL data (n=36,829). LTL was quantified using multiplex quantitative polymerase chain reaction. Among 445,895 participants without AF at enrollment, 2,851 were hospitalized for HF (mean age 63.1±5.8, 63.3% male), while 313 with AF (mean age 64.3±5.3, 68.4% male) experienced HF hospitalization. Shorter LTL correlated significantly with HF hospitalization in both non-AF (826.8±117.7 vs 797.9±115.5, P < 0.001) and AF groups (804.8±116.1 vs 789.2±115.9, P < 0.001). Categorized into quartiles, shorter LTL consistently associated with higher HF hospitalization rates in both non-AF (P for trend < 0.001) and AF groups (P for trend = 0.022). Adjusting for age, sex, and cardiovascular risk factors, longer LTL correlated with reduced HF risk (HR, 0.87; 95% CI, 0.77-0.98; P = 0.017), independent of AF presence (P for interaction=0.629). This study establishes an association between shorter LTL and increased HF hospitalization rates, regardless of AF presence. These findings underscore the significance of LTL as a potential prognostic biomarker for HF, emphasizing its relevance in both AF and non-AF populations

#2751 CD14++CD16+ monocytes and CD8+ T cells are independently associated with annual change in eGFR and proteinuria in kidney transplant recipients

Abstract Background and Aims Immune cellular responses are implicated in all clinical aspects of kidney transplantation. There is little data regarding the additional value of regular monitoring of immune cells subsets expression in kidney transplant recipients (KTRs). The aim of our prospective study was a longitudinal follow-up analysis of monocytes subpopulations, natural killer (NK) cells and lymphocytes subsets including regulatory T cells (Tregs) in the circulation of KTRs and potential clinical correlations. Method 48 stable KTRs were initially enrolled. All KTRs were under immunosuppressive regimen with corticosteroids, mycophenolate mofetil or mycophenolate acid and calcineurin inhibitors (CNIs). Exclusion criteria were history or development during follow-up of acute rejection, cardiovascular disease, malignancy and active or chronic infections. Patients were followed for 12 months. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16+ and CD14+CD16++ absolute values and percentages out of total monocytes and NK cells (CD3+CD16+56+), CD3-CD19+ B lymphocytes, CD3+ CD4+ T cells, CD3+CD8+ T cells and Tregs (CD4+CD25+ FoxP3+) absolute values and percentages out of total lymphocytes were measured by flow cytometry at baseline (T0) and after 12 months (T1). Clinical and laboratory parameters were recorded at T0 and T1. Delta (Δ) eGFR and Δ spot urine protein to creatinine ratio (ΔUPCR) were defined as their respective differences between T1 and T0. Likewise, Delta (Δ) of immune cells subtypes or laboratory indices was defined as their respective difference between T1 and T0. Results 35 KTRs (mean age 53 ± 9.28 years, 71% males, mean transplant vintage 96 ± 66 months, 63% on Tacrolimus and 37% on Cyclosporine) were included in the final analysis. Significant differences were observed between T0 and T1 in monocytes number (653 ± 244 and 538 ± 197/μL respectively, p = 0.001), monocytes percentage (7.6 ± 2.9 and 6.6 ± 2.2% respectively, p = 0.006) as well as in the number of classical CD14++CD16- monocytes (534 ± 225 and 452 ± 185/μL respectively, p = 0.04). The rest immune cells subsets did not show any significant differences between T0 and T1. Mean eGFR declined from 58 ± 17 at T0 to 53 ± 18 ml/min/1.73 m2 at T1 (p = 0.004). No significant changes were observed between T0 and T1 in median UPCR [0.16 (IRQ, 0.09-0.56) at T0 and 0.16 (IQR, 0.10-0.70) gr protein/gr creatine at T1, p = 0.489], in median CRP [4.0 (IQR, 3-7) at T0 and 5 (IQR, 2.5-7.5) mg/L) at T1, p = 0.919], in mean ESR (20 ± 14 at T0 and 22 ± 19 mm/hour at T1, p = 0.381) or other parameters, including CNIs blood levels. ΔeGFR was correlated with the T0 percentage of monocytes (rho = 0.359, p = 0.037), the T0 number and T0 percentage of CD14++CD16+ monocytes (rho= 0.502, p = 0.003 and rho = 0.438, p = 0.008 respectively). On the other hand, a borderline inverse correlation was observed between ΔeGFR and ΔCD14++CD16+ monocytes number (rho = −0.339, p = 0.05). Additional correlates of ΔeGFR included serum albumin at T0 (rho = 0.395, p = 0.021) and Δuric acid (rho = 0.567, p = 0.000). At stepwise linear regression analysis, CD14++CD16+ monocytes (β = 0.338, p = 0.04) and Δuric acid (β = 0.477, p = 0.006) remained independent significant correlates of ΔeGFR. ΔUPCR was significantly correlated with the percentage of B-lymphocytes (rho = 0.385, p = 0.027) and CD4+ T-cells (rho = 0.352, p = 0.044) at T0, and inversely correlated with the T0 percentage of T-lymphocytes (rho = −0.402, p = 0.02) and CD8+ T cells (rho = −0.603, p = 0.000) as well as with Δhemoglobin (rho = −0.385, p = 0.027). At stepwise linear regression analysis, only the CD8+ T cells percentage at T0 remained independently correlated to ΔUPCR (β = –0.379, p = 0.03). Conclusion The results of our study indicate that intermediate CD14++CD16+ monocytes are associated with annual eGFR change whereas CD8+ T cells negatively correlate with the annual trend of proteinuria change in KTRs. Further research is needed to clarify underlying pathophysiological mechanisms for these findings. Finally, future studies including larger cohorts and with longer follow-up are required to specify the potential utility of immune subpopulations monitoring as potential prognostic biomarkers in KTRs.

Identification of established and novel extracellular matrix components in glioblastoma as targets for angiogenesis and prognosis.

Glioblastomas (GBM) are aggressive tumors known for their heterogeneity, rapid proliferation, treatment resistance, and extensive vasculature. Angiogenesis, the formation of new vessels, involves endothelial cell (EC) migration and proliferation. Various extracellular matrix (ECM) molecules regulate EC survival, migration, and proliferation. Culturing human brain EC (HBMEC) on GBM-derived ECM revealed a decrease in EC numbers compared to controls. Through in silico analysis, we explored ECM gene expression differences between GBM and brain normal glia cells and the impact of GBM microenvironment on EC ECM transcripts. ECM molecules such as collagen alpha chains (COL4A1, COL4A2, p < 0.0001); laminin alpha (LAMA4), beta (LAMB2), and gamma (LAMC1) chains (p < 0.0005); neurocan (NCAN), brevican (BCAN) and versican (VCAN) (p < 0.0005); hyaluronan synthase (HAS) 2 and metalloprotease (MMP) 2 (p < 0.005); MMP inhibitors (TIMP1-4, p < 0.0005), transforming growth factor beta-1 (TGFB1) and integrin alpha (ITGA3/5) (p < 0.05) and beta (ITGB1, p < 0.0005) chains showed increased expression in GBM. Additionally, GBM-influenced EC exhibited elevated expression of COL5A3, COL6A1, COL22A1 and COL27A1 (p < 0.01); LAMA1, LAMB1 (p < 0.001); fibulins (FBLN1/2, p < 0.01); MMP9, HAS1, ITGA3, TGFB1, and wingless-related integration site 9B (WNT9B) (p < 0.01) compared to normal EC. Some of these molecules: COL5A1/3, COL6A1, COL22/27A1, FBLN1/2, ITGA3/5, ITGB1 and LAMA1/B1 (p < 0.01); NCAN, HAS1, MMP2/9, TIMP1/2 and TGFB1 (p < 0.05) correlated with GBM patient survival. In conclusion, this study identified both established and novel ECM molecules regulating GBM angiogenesis, suggesting NCAN and COL27A1 are new potential prognostic biomarkers for GBM.

Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non‐small cell lung cancer

AbstractBackgroundNon‐small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5‐year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required.MethodsThe UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain‐of‐function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms.ResultsNR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real‐world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co‐expressed genes are involved in many cancer‐related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC.ConclusionsNR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.

Retraction Note: Systematic pan-cancer analysis identifies transmembrane protein 158 as a potential therapeutic, prognostic and immunological biomarker.

Retraction Note: Systematic pan-cancer analysis identifies transmembrane protein 158 as a potential therapeutic, prognostic and immunological biomarker.

Identification of potential biomarkers for pancreatic ductal adenocarcinoma: a bioinformatics analysis.

PDA is an aggressive cancer with a 5-year survival rate, which is very low. There is no effective prognosis or therapy for PDA because of the lack of target biomarkers. The objective of this article is to identify the target biomarkers for PDA using a bioinformatics approach. In this work, we have analysed the three microarray datasets from the NCBI GEO database. We used the Geo2R tool to analyse the microarray data with the Benjamini and Hochberg false discovery rate method, and the significance level cut-off was set to 0.05. We have identified 659 DEGs from the datasets. There are a total of 15 hub genes that were selected from the PPI network constructed using the STRING application. Furthermore, these 15 genes were evaluated on PDA patients using TCGA and GTEx databases in (GEPIA). The online tool DAVID was used to analyse the functional annotation information for the DEGs. The functional pathway enrichment was performed on the GO and KEGG. The hub genes were mainly enriched for cell division, chromosome segregation, protein binding and microtubule binding. Further, the gene alteration study was performed using the cBioportal tool and screened out six hub genes (ASPM, CENPF, BIRC5, TTK, DLGAP5, and TOP2A) with a high alteration rate in PDA samples. Furthermore, Kaplan-Meier survival analysis was performed on the six hub genes and identified poor-survival outcomes that may be involved in tumorigenesis and PDA development. So, this study concludes that, these six hub genes may be potential prognostic biomarkers for PDA.

Tertiary lymphoid structures as a potential prognostic biomarker for combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA), as a rare primary hepatic tumor, is challenging to accurately assess in terms of the clinical outcomes and prognostic risk factors in patients. This study aimed to clarify the function of tertiary lymphoid structure (TLS) status in predicting the outcome of cHCC-CCA and to preliminarily explore the possible mechanism of TLS formation. The TLSs, with different spatial distributions and densities, of 137 cHCC-CCA were quantified, and their association with prognosis was assessed by Cox regression and Kaplan-Meier analyses. We further validated TLS possible efficacy in predicting immunotherapy responsiveness in two cHCC-CCA case reports. TLS composition and its relationship to CXCL12 expression were analysed by fluorescent multiplex immunohistochemistry. A high intratumoural TLS score was correlated with prolonged survival, whereas a high TLS density in adjacent tissue indicated a worse prognosis in cHCC-CCA. Mature TLSs were related to favorable outcomes and showed more CD8 + T cells infiltrating tumor tissues. We further divided the cHCC-CCA patients into four immune grades by combining the peri-TLS and intra-TLS, and these grades were an independent prognostic factor. In addition, our reported cases suggested a potential value of TLS in predicting immunotherapy response in cHCC-CCA patients. Our findings suggested that CXCL12 expression in cHCC-CCA tissue was significantly correlated with TLS presence. The spatial distribution and density of TLSs revealing the characteristics of the cHCC-CCA immune microenvironment, significantly correlated with prognosis and provided a potential immunotherapy response biomarker for cHCC-CCA.

NGEF is a potential prognostic biomarker and could serve as an indicator for immunotherapy and chemotherapy in lung adenocarcinoma.

Neuronal guanine nucleotide exchange factor (NGEF) plays a key role in several cancers; however, its role in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to evaluate the efficacy of NGEF as a prognostic biomarker and potential therapeutic target for LUAD. NGEF expression data for multiple cancers and LUAD were downloaded from multiple databases. The high- and low-NGEF expression groups were constructed based on median NGEF expression in LUAD samples, and then performed Kaplan-Meier survival analysis. Differentially expressed genes (DEGs) from the two NGEF expression groups were screened and applied to construct a protein-protein interaction network. The primary pathways were obtained using gene set enrichment analysis. The associations between NGEF expression and clinical characteristics, immune infiltration, immune checkpoint inhibitors (ICIs), sensitivity to chemotherapy, and tumor mutation burden (TMB) were investigated using R. Levels of NGEF expression in the lung tissue was validated using single-cell RNA sequencing, quantitative polymerase chain reaction (qPCR), immunohistochemical staining, and western blot analysis. The expression of NGEF mRNA was upregulated in multiple cancers. mRNA and protein expression levels of NGEF were higher in patients with LUAD than in controls, as validated using qPCR and western blot. High NGEF expression was an independent prognostic factor for LUAD and was associated with advanced tumor stage, large tumor size, more lymph node metastasis, and worse overall survival (OS). A total of 182 overlapping DEGs were screened between The Cancer Genome Atlas and GSE31210, among which the top 20 hub genes were identified. NGEF expression was mainly enriched in the pathways of apoptosis, cell cycle, and DNA replication. Moreover, elevated NGEF expression were associated with a high fraction of activated memory CD4+ T cells and M0 macrophages; elevated expression levels of the ICIs: programmed cell death 1 and programmed cell death 1 ligand 1 expression; higher TMB; and better sensitivity to bortezomib, docetaxel, paclitaxel, and parthenolide, but less sensitivity to axitinib and metformin. NGEF expression is upregulated in LUAD and is significantly associated with tumor stages, OS probability, immune infiltration, immunotherapy response, and chemotherapy response. NGEF may be a potential diagnostic and prognostic biomarker and therapeutic target in LUAD.

A Comprehensive Pan-Cancer Analysis Reveals Cyclin-Dependent Kinase Inhibitor 2A Gene as a Potential Diagnostic and Prognostic Biomarker in Colon Adenocarcinoma

A Comprehensive Pan-Cancer Analysis Reveals Cyclin-Dependent Kinase Inhibitor 2A Gene as a Potential Diagnostic and Prognostic Biomarker in Colon Adenocarcinoma

LTF as a Potential Prognostic and Immunological Biomarker in Glioblastoma.

The lactoferrin (LTF) gene behaves like a tumor suppressor gene in diverse tumors, such as renal cancer, nasopharyngeal carcinoma and gastric cancer. However, the prognostic value of LTF expression in patients with glioblastoma remains unclear. In this study, the expression levels of LTF in patients with GBM were investigated in TCGA, GEPIA, CGGA and GEO database, and a survival analysis of LTF based on TCGA and CGGA was performed. Furthermore, the present study demonstrated the LTF gene co-expression, PPI network, KEGG/GO enrichment and immune cell infiltration analysis on TCGA and TIMER2.0 database. We found that LTF expression was significantly upregulated in GBM samples compared with normal samples and other glioma samples, and Kaplan-Meier analysis demonstrated that the overexpression of LTF were significantly associated with worse overall survival (OS) and 5-year OS in GBM patients (P < 0.05). KEGG/GO enrichment analysis demonstrated that functions of LTF concentrated in immune and inflammatory response and peptidase regulation (P < 0.05). Immune cell infiltration analysis presented that high LTF expression exhibited dysregulated immune infiltration (i.e., CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells and cancer associated fibroblast). LTF was upregulated in tumors and correlated with worse OS in GBM patients, and LTF might function as an oncogene via inducing dysregulated immune infiltration in GBM.

Peroxiredoxin 2 as a potential prognostic biomarker associated with angiogenesis in cervical squamous cell cancer.

Peroxiredoxins (Prxs) are a ubiquitously expressed family of antioxidant enzymes that either facilitate or inhibit tumorigenesis, depending on the cancer type and Prx isoform. Prx2 is a typical Prx that has a dual role in tumorigenesis and tumor progression. However, the expression of Prx2 and its precise role in cervical cancer remains to be elucidated. Therefore, the present study aimed to investigate the expression of Prx2 and its association with the progression and prognosis of cervical squamous cell cancer (CSCC). In the present study, the clinicopathological data of 105 patients diagnosed with CSCC were collected from the medical record system at Jingzhou Central Hospital, Tongji Medical College of Huazhong University of Science and Technology (Jingzhou, China). Prx2 protein was also detected in 105 CSCC tissues and 40 adjacent peri-tumoral tissues by immunohistochemical staining. The relationships between Prx2 expression and clinicopathological features, vascular endothelial growth factor A (VEGF-A) expression and micro-vessel density (MVD) in CSCC were then analyzed. Progression-free survival (PFS) was also assessed using both univariate and multivariate analyses. The results of the present study demonstrated that the expression of Prx2 was upregulated in CSCC tissues compared with the adjacent peri-tumoral tissues (P<0.001). In addition, higher Prx2 expression was associated with greater depth of stromal invasion (P=0.023) and positive lymph vascular space invasion (P=0.044), while the Prx2 expression level was not associated with age, tumor size, histological grade, lymph node (LN) metastasis or International Federation of Gynecology and Obstetrics (FIGO) stage (all P>0.05). Furthermore, increased Prx2 expression was associated with high MVD (P=0.016), while expression of VEGF-A was not associated with Prx2 expression (P>0.05). Kaplan-Meier analysis showed that patients with high Prx2 expression (log-rank test, P=0.039), high MVD (log-rank test, P=0.015), a higher FIGO stage (log-rank test, P=0.021) and LN metastasis (log-rank test, P=0.022) had a shorter PFS time than patients with low Prx2 expression, low MVD, a lower FIGO stage and without LN metastasis, respectively. Cox proportional hazard regression analysis revealed that expression of Prx2 [hazard ratio (HR), 2.551; 95% confidence interval (CI), 1.056-6.162; P=0.037], MVD (HR, 2.436; CI, 1.034-5.735; P=0.042) and FIGO stage (HR, 1.543; CI, 1.027-2.319; P=0.037) were independent factors for PFS time. In conclusion, the results of the present study suggested that Prx2 could act as a potential biomarker for predicting CSCC progression and prognosis and could be a novel target for antiangiogenic therapy of CSCC.

1,25-Dihydroxyvitamin D3 Suppresses Prognostic Survival Biomarkers Associated with Cell Cycle and Actin Organization in a Non-Malignant African American Prostate Cell Line.

Vitamin D3 is a steroid hormone that confers anti-tumorigenic properties in prostate cells. Serum vitamin D3 deficiency has been associated with advanced prostate cancer (PCa), particularly affecting African American (AA) men. Therefore, elucidating the pleiotropic effects of vitamin D on signaling pathways, essential to maintaining non-malignancy, may provide additional drug targets to mitigate disparate outcomes for men with PCa, especially AA men. We conducted RNA sequencing on an AA non-malignant prostate cell line, RC-77N/E, comparing untreated cells to those treated with 10 nM of vitamin D3 metabolite, 1α,25(OH)2D3, at 24 h. Differential gene expression analysis revealed 1601 significant genes affected by 1α,25(OH)2D3 treatment. Pathway enrichment analysis predicted 1α,25(OH)2D3- mediated repression of prostate cancer, cell proliferation, actin cytoskeletal, and actin-related signaling pathways (p < 0.05). Prioritizing genes with vitamin D response elements and associating expression levels with overall survival (OS) in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) cohort, we identified ANLN (Anillin) and ECT2 (Epithelial Cell Transforming 2) as potential prognostic PCa biomarkers. Both genes were strongly correlated and significantly downregulated by 1α,25(OH)2D3 treatment, where low expression was statistically associated with better overall survival outcomes in the TCGA PRAD public cohort. Increased ANLN and ECT2 mRNA gene expression was significantly associated with PCa, and Gleason scores using both the TCGA cohort (p < 0.05) and an AA non-malignant/tumor-matched cohort. Our findings suggest 1α,25(OH)2D3 regulation of these biomarkers may be significant for PCa prevention. In addition, 1α,25(OH)2D3 could be used as an adjuvant treatment targeting actin cytoskeleton signaling and actin cytoskeleton-related signaling pathways, particularly among AA men.

F10 Gene Expression and Ethnic Disparities Present in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) presents a significant health concern, particularly among Hispanic women in the United States, who exhibit a disproportionately higher chance of developing an advanced disease when compared to the non-Hispanic population. Emerging evidence suggests coagulation factor X, encoded by the F10 gene, has a potential role in inhibiting cancer cell migration. However, comprehensive investigations into the differential expression patterns of F10 in Hispanic versus non-Hispanic females remain limited. RNA-sequencing data were acquired from the TCGA database for white female patients, 166 non-Hispanic and 25 Hispanic. A statistically significant (p < 0.05) 2.06-fold increase in F10 expression levels was detected in disease-free tumors compared to recurrent PTC tumors. Furthermore, an increase in F10 gene expression levels was also observed, corresponding to approximately a 1.74-fold increase in non-Hispanic patients compared to Hispanic patients. The probability of tumor recurrence was 1.82 times higher in the cohort with low expression of F10 compared to the high-expression cohort, correlating with the lower disease-free rates observed in the Hispanic patient cohort when compared to non-Hispanics. This finding underscores the relevance of ethnic disparities in molecular profiles for understanding cancer susceptibility. Identifying F10 as a potential prognostic biomarker highlights avenues for targeted interventions and contributes to improving diagnostic and treatment strategies for diverse patient populations.

EMP1 correlated with cancer progression and immune characteristics in pan-cancer and ovarian cancer.

This study examines the prognostic role and immunological relevance of EMP1 (epithelial membrane protein-1) in a pan-cancer analysis, with a focus on ovarian cancer. Utilizing data from TCGA, CCLE, and GTEx databases, we assessed EMP1 mRNA expression and its correlation with tumor progression, prognosis, and immune microenvironment across various cancers. Our results indicate that EMP1 expression is significantly associated with poor prognosis in multiple cancer types, including ovarian, bladder, testicular, pancreatic, breast, brain, and uveal melanoma. Immune-related analyses reveal a positive correlation between EMP1 and immune cell infiltration, particularly neutrophils, macrophages, and dendritic cells, as well as high expression of immune checkpoint such as CD274, HAVCR2, IL10, PDCD1LG2, and TGFB1 in most tumors. In vivo experiments confirm that EMP1 promotes ovarian cancer cell proliferation, metastasis, and invasion. In conclusion, EMP1 emerges as a potential prognostic biomarker and therapeutic target in various cancers, particularly ovarian cancer, due to its influence on tumor progression and immune cell dynamics. Further research is warranted to elucidate the precise mechanisms of EMP1 in cancer biology and to translate these findings into clinical applications.

Epigenetic silencing of LDHB promotes hepatocellular carcinoma by remodeling the tumor microenvironment

Lactate dehydrogenase B (LDHB) reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate and expressed in various malignancies. However, the role of LDHB in modulating immune responses against hepatocellular carcinoma (HCC) remains largely unknown. Here, we found that down-regulation of lactate dehydrogenase B (LDHB) was coupled with the promoter hypermethylation and knocking down the DNA methyltransferase 3A (DNMT 3A) restored LDHB expression levels in HCC cell lines. Bioinformatics analysis of the HCC cohort from The Cancer Genome Atlas revealed a significant positive correlation between LDHB expression and immune regulatory signaling pathways and immune cell infiltrations. Moreover, immune checkpoint inhibitors (ICIs) have shown considerable promise for HCC treatment and patients with higher LDHB expression responded better to ICIs. Finally, we found that overexpression of LDHB suppressed HCC growth in immunocompetent but not in immunodeficient mice, suggesting that the host immune system was involved in the LDHB-medicated tumor suppression. Our findings indicate that DNMT3A-mediated epigenetic silencing of LDHB may contribute to HCC progression through remodeling the tumor immune microenvironment, and LDHB may become a potential prognostic biomarker and therapeutic target for HCC immunotherapy.

Current knowledge about immunotherapy resistance for melanoma and potential predictive and prognostic biomarkers

Melanoma still reaches thousands of new diagnoses per year, and its aggressiveness makes recovery challenging, especially for those with stage III/IV unresectable melanoma. Immunotherapy, emerging as a beacon of hope, stands at the forefront of treatments for advanced melanoma. This review delves into the various immunotherapeutic strategies, prominently featuring cytokine immunotherapy, adoptive cell therapy, immune checkpoint inhibitors, and vaccinations. Among these, immune checkpoint inhibitors, notably anti-programmed cell death-1 (PD-1) and anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibodies, emerge as the leading strategy. However, a significant subset of melanoma patients remains unresponsive to these inhibitors, underscoring the need for potent biomarkers. Efficient biomarkers have the potential to revolutionize the therapeutic landscape by facilitating the design of personalized treatments for patients with melanoma. This comprehensive review highlights the latest advancements in melanoma immunotherapy and potential biomarkers at the epicenter of recent research endeavors.

Parallel Cerebrospinal Fluid and Serum Temporal Profile Assessment of Axonal Injury Biomarkers Neurofilament-Light Chain and Phosphorylated Neurofilament-Heavy Chain: Associations With Patient Outcome in Moderate-Severe Traumatic Brain Injury.

Neurofilament-light chain (NF-L) and phosphorylated neurofilament-heavy chain (pNF-H) are axonal proteins that have been reported as potential diagnostic and prognostic biomarkers in traumatic brain injury (TBI). However, detailed temporal profiles for these proteins in blood, and interrelationships in the acute and chronic time periods post-TBI have not been established. Our objectives were: 1) to characterize acute-to-chronic serum NF-L and pNF-H profiles after moderate-severe TBI, as well as acute cerebrospinal fluid (CSF) levels; 2) to evaluate CSF and serum NF-L and pNF-H associations with each other; and 3) to assess biomarker associations with global patient outcome using both the Glasgow Outcome Scale-Extended (GOS-E) and Disability Rating Scale (DRS). In this multi-cohort study, we measured serum and CSF NF-L and pNF-H levels in samples collected from two clinical cohorts (University of Pittsburgh [UPITT] and Baylor College of Medicine [BCM]) of individuals with moderate-severe TBI. The UPITT cohort includes 279 subjects from an observational cohort study; we obtained serum (n = 277 unique subjects) and CSF (n = 95 unique subjects) daily for 1 week, and serum every 2 weeks for 6 months. The BCM cohort included 103 subjects from a previous randomized clinical trial of erythropoietin and blood transfusion threshold after severe TBI, which showed no effect on neurological outcome between treatment arms; serum (n = 99 unique subjects) and CSF (n = 54 unique subjects) NF-L and pNF-H levels were measured at least daily during Days (D) 0-10 post-injury. GOS-E and DRS were assessed at 6 months (both cohorts) and 12 months (UPITT cohort only). Results show serum NF-L and pNF-H gradually rise during the first 10 days and peak at D20-30 post-injury. In the UPITT cohort, acute (D0-6) NF-L and pNF-H levels correlate within CSF and serum (Spearman r = 0.44-0.48; p < 0.05). In the UPITT cohort, acute NF-L CSF and serum levels, as well as chronic (Months [M]2-6) serum NF-L levels, were higher among individuals with unfavorable GOS-E and worse DRS at 12 months (p < 0.05, all comparisons). In the BCM cohort, higher acute serum NF-L levels were also associated with unfavorable GOS-E. Higher pNF-H serum concentrations (D0-6 and M2-6), but not CSF pNF-H, were associated with unfavorable GOS-E and worse DRS (p < 0.05, all comparisons) in the UPITT cohort. Relationships between biomarker levels and favorable outcome persisted after controlling for age, sex, and Glasgow Coma Scale. This study shows for the first time that serum levels of NF-L and pNF-H peak at D20-30 post-TBI. Serum NF-L levels, and to a lesser extent pNF-H levels, are robustly associated with global patient outcomes and disability after moderate-severe TBI. Further studies on clinical utility as prognosis and treatment-response indicators are needed.

The CpG Island Methylator Phenotype Status in Synchronous and Solitary Primary Colorectal Cancers: Prognosis and Effective Therapeutic Drug Prediction.

Synchronous colorectal cancer (sCRC) is characterized by the occurrence of more than one tumor within six months of detecting the first tumor. Evidence suggests that sCRC might be more common in the serrated neoplasia pathway, marked by the CpG island methylator phenotype (CIMP), than in the chromosomal instability pathway (CIN). An increasing number of studies propose that CIMP could serve as a potential epigenetic predictor or prognostic biomarker of sCRC. Therapeutic drugs already used for treating CIMP-positive colorectal cancers (CRCs) are reviewed and drug selections for sCRC patients are discussed.

Pan-cancer analysis of LRRC59 with a focus on prognostic and immunological roles in hepatocellular carcinoma.

LRRC59 is a leucine-rich repeats-containing protein located in the endoplasmic reticulum (ER), it serves as a prognostic marker in several cancers. However, there has been no systematic analysis of its role in the tumor immune microenvironment, nor its predictive value of prognosis and immunotherapy response in different cancers. A comprehensive pan-cancer analysis of LRRC59 was conducted from various databases to elucidate the associations between its expression and the prognosis of cancer, genetic alterations, tumor metabolism, and tumor immunity. Additionally, further functional assays were performed in hepatocellular carcinoma (HCC) to study its biological role in regulating cell proliferation, migration, apoptosis, cell cycle arrest, and sensitivity to immunotherapy. The pan-cancer analysis reveals a significant upregulation of LRRC59 in pan-cancer, and its overexpression is correlated with unfavorable prognosis in cancer patients. LRRC59 is negatively correlated with immune cell infiltration, tumor purity estimation, and immune checkpoint genes. Finally, the validation in HCC demonstrates LRRC59 is significantly overexpressed in cancer tissue and cell lines, and its knockdown inhibits cell proliferation and migration, promotes cell apoptosis, induces cell cycle arrest, and enhances the sensitivity to immunotherapy in HCC cells. LRRC59 emerges as a novel potential prognostic biomarker across malignancies, offering promise for anti-cancer drugs and immunotherapy.