Independent Prognostic Marker Research Articles

Evaluation of the incidence, predictors, risk assessment scores and outcomes of thromboembolism in a cohort of Egyptian NHL patients - Real World Experience.

Non-Hodgkin's Lymphoma (NHL) is the most common subtype of lymphoma. The incidence of venous thromboembolism (VTE) in aggressive NHL was estimated recently to be 11%. Several risk assessment scores and factors are available to help identify cancer patients at risk for developing VTE. Patients with a pathologically confirmed diagnosis of NHL were identified at the Oncology Center of Mansoura University. The study included 777 patients: 719 with DLBCL-NOS, 26 with Anaplastic-B-cell, and 32 with T-cell-rich-NHL. Data were retrospectively collected from electronic medical records, including clinical, radiological, and laboratory information related to VTE and NHL. The median age at NHL diagnosis was 53 years, (range: 18-98). There was a male predominance, 51.4% of the cases. At initial lymphoma diagnosis, VTE was identified in 46 (5.9%) patients, and 61 (7.9%) patients experienced VTE while undergoing chemotherapy. According to logistic regression analysis, a PS (performance status) ≥ 2, bulky lesions, and mediastinal masses were significant predictors of VTE at presentation, with P-values of 0.022, 0.002, and < 0.001, respectively. Meanwhile, NHL patients who developed VTE during chemotherapy had significantly poorer PS, higher absolute neutrophilic counts (ANC), neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels than lymphoma patients without VTE, with P-values of 0.003, 0.034, 0.049, 0.01and 0.007, respectively, as determined by multivariate analysis. The ROC curve identified the cut-off values of 4.875 × 109/L for ANC, 2.985 for NLR, 144.85 for PLR, and 417.5 U/L for LDH as potential markers for predicting VTE in NHL patients. Patients with a PS ≥ 2 and values exceeding these cut-offs for ANC, NLR, and PLR experienced significantly higher incidences of VTE than other groups, with P-values of 0.003, < 0.001, < 0.001, and < 0.001, respectively. At the end of the follow-up, the overall survival was significantly shortened by VTE occurring during chemotherapy, hypoalbuminemia, intermediate-high and high international prognostic index (IPI) scores (intermediate-high and high), responses other than CR and relapse, all with P-values < 0.05. ECOG PS and Inflammatory markers such as NLR, PLR, and neutrophilic count could serve as predictors of the development of thrombotic events in patients with NHL-DLBCL. Additionally, the occurrence of VTE during chemotherapy is an independent poor prognostic marker for overall survival (OS).

Frailty and Cardiovascular Health.

The incidence of frailty and cardiovascular disease (CVD) increases as the population ages. There is a bidirectional relationship between frailty and CVD, and both conditions share several risk factors and underlying biological mechanisms. Frailty has been established as an independent prognostic marker in patients with CVD. Moreover, its presence significantly influences both primary and secondary prevention strategies for adults with CVD while also posing a barrier to the inclusion of these patients in pivotal clinical trials and advanced cardiac interventions. This review discusses the current knowledge base on the relationship between frailty and CVD, how managing CVD risk factors can modify frailty, the influence of frailty on CVD management, and future directions for frailty detection and modification in patients with CVD.

Tertiary Lymphoid Structures in Brain Metastases of Lung Cancer: Prognostic Significance and Correlation With Clinical Outcomes.

The prognosis of patients with brain metastases (BMs) originating from lung cancer remains poor, despite advancements in treatment strategies. The role of tertiary lymphoid structures (TLSs) within the tumor immune microenvironment of BMs has not been extensively explored. This study utilized patient-derived clinical samples from 17 patients with histologically confirmed BMs of lung cancer, undergoing surgical resection. Immunohistochemistry was employed to analyze the presence and characteristics of TLS and tumor-infiltrating lymphocytes (TILs) within BM tissues, correlating these with clinical outcomes. TLSs, albeit in their immature form, were identified within BM tissues, distinguishing them from their mature counterparts in primary lung cancer tissues. A significant correlation between TLS density (but not TIL density) and improved postoperative survival was observed, underscoring the potential of TLS density as an independent prognostic marker. Furthermore, TLS density did not correlate with the Graded Prognostic Assessment (GPA) index, suggesting its unique prognostic value beyond conventional predictors. Our findings reveal the presence of TLSs in lung cancer-derived BMs and highlight their prognostic significance, independent of the GPA index. The identification of TLS within the unique central nervous system tumor microenvironment offers new insights into the immune landscape of BMs and suggests potential avenues for immunotherapeutic interventions targeting these structures to improve patient outcomes.

PDCL3 as a prognostic factor and associated with the VEGF signaling pathway in glioma.

New targeted drugs about angiogenesis could develop the treatment of glioma. We aimed to explore the role of phosducin like 3 (PDCL3) in angiogenesis of glioma. RNA sequencing data and matched clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. To screen for the reliable genes with the filtering analyses, survival, multivariate Cox, receiver operating characteristic (ROC) curve filtration, and clinical correlation analyses were performed. The PDCL3 gene was validated by immunohistochemistry as a reliable gene for further analysis. Then we used the combined data of TCGA and Genotype-Tissue Expression from UCSC to detect the differential gene expression of PDCL3. Related signal pathways in glioma were explored by the gene set enrichment analysis and co-expression analysis. Lastly, we performed in vitro experiments to verify the gene functions and related mechanisms. The three filtering analyses and immunostaining indicated that the expression of PDCL3 in glioma tissues was higher than the normal tissues. Gene function analysis showed that PDCL3 activated the vascular endothelial growth factor (VEGF) signal pathway, and its mechanism was related to pathways in cancer, like NOD like receptor signaling pathway, the RIG-I like receptor signaling pathway and the P53 signaling pathway by MAPK/AKT in gliomas. This suggested that the proliferation, migration and invasion of glioma cells might be inhibited by the downregulation of PDCL3 in vitro, which may be related to the activation of VEGF signaling pathway. We demonstrated that PDCL3 could function as an independent adverse prognostic marker in glioma. Its pro-oncogenic mechanism may be related to the VEGF signaling pathway.

Percent Predicted Peak Exercise Oxygen Pulse Provides Insights Into Ventricular-Vascular Response and Prognosticates HFpEF

BackgroundPeak oxygen consumption and oxygen pulse along with their respective percent predicted measures are gold standards of exercise capacity. To date, no studies have investigated the relationship between percent predicted peak oxygen pulse (%PredO2P) and ventricular-vascular response (VVR) and the association of %PredO2P with all-cause mortality in heart failure with preserved ejection fraction (HFpEF) patients. ObjectivesThe authors investigated the association between: 1) CPET measures of %PredO2P and VVR; and 2) %PredO2P and all-cause mortality in HFpEF patients. MethodsOur cohort of 154 HFpEF patients underwent invasive CPET and were grouped into %PredO2P tertiles. The association between percent predicted Fick components and markers of VVR (ie, proportionate pulse pressure, effective arterial elastance) was determined with correlation analysis. The Cox proportional hazards model was used to identify predictors of mortality. ResultsThe participants’ mean age was 57 ± 15 years. Higher %PredO2P correlated with higher exercise capacity. In terms of VVR, higher %PredO2P correlated with a lower pressure for a given preload (effective arterial elastance r = −0.45, P < 0.001 and proportionate pulse pressure r = −0.22, P = 0.008). %PredO2P distinguished normal and abnormal percent predicted peak stroke volume and correlated positively with %PredVO2 (r = 0.61, P < 0.001). Participants had a median follow-up time of 5.6 years and 15% death. Adjusted for age and body mass index, there was a 5% relative reduction in mortality (HR: 0.95, 95% CI: 0.92-0.98, P = 0.003) for every percent increase in %PredO2P. ConclusionsIn HFpEF, %PredO2P is a VVR marker that can stratify invasive parameters such as percent predicted peak stroke volume. %PredO2P is an independent prognostic marker for all-cause mortality and those with higher %PredO2P exhibited longer survival.

ADH4—a potential prognostic marker for hepatocellular carcinoma with possible immune-related implications

ObjectiveThis study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment.MethodsHCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues.ResultsADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy.ConclusionThis study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

Epidermal growth factor receptor and programmed cell death-1 expression levels in peripheral T cell subsets of patients with non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths, in part due to its late diagnosis. Increased epidermal growth factor receptor (EGFR) expression in cancer cells is associated with a poor prognosis, and EGFR tyrosine kinase inhibitors are widely used in cancer treatment. This study aimed to clarify the relationship between EGFR expression on T cells and cancer prognosis in patients with non-small cell lung cancer (NSCLC). Forty patients with NSCLC and 40 healthy volunteers were included in this study. Peripheral CD4+T helper (Th1, Th2, Th9, Th17, Th1Th17, follicular and peripheral Th) and cytotoxic T lymphocyte (CD8+follicular and peripheral T) subsets were identified with flow cytometry according to their chemokine receptors. EGFR expression on T lymphocytes in relation to overall survival (OS) was investigated in patients with NSCLC. The patients [mean age (min-max) = 64.03 (45-83); 20 stage I-III and 20 stage IV] had increased EGFR expression on CD3+T, CD4+Th, Th1, Th2, and Th17 cells compared to the controls (p < 0.05). High EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells was associated with poor OS. Also, PD-1 expression on lymphocytes, CD3+T, and Th cells was increased in patients with NSCLC compared to controls. The high expression of EGFR and PD-1 on Th cells and the reduced percentage of lymphocytes and Th cells, especially in stage IV patients with NSCLC, revealed that increased EGFR activity may trigger apoptosis of Th cells and promote the development of metastases, while high EGFR expression on CD3+T, CD4+Th, Th1, and Th2 cells may be an independent poor prognostic marker in NSCLC.

Pan-cancer analysis of TMEM45A and exploration of its prognostic value and mechanism in gastric cancer.

Cancer is a major category of diseases that need to be addressed urgently, bringing a huge burden to the world. Gastric cancer (GC) is a frequent malignant tumor of the digestive system with the highest incidence and mortality rate among all tumors. The purpose of this study was to explore the mechanism of action of TMEM45A in pan-cancer and gastric cancer. First, GEO and TCGA database were employed to analyze the expression of TMEM45A in GC patients. Then, we determined the association between TMEM45A expression and survival of GC patients using the Kaplan-Meier Plotter database and TCGA database and verified the accuracy of TMEM45A in predicting prognosis. Next, we analyzed the effect of CTHRC expression on TIICs in GC tissues. A prognostic model was constructed using immunomodulatory genes associated with TMEM45A. The specificity and accuracy of the model were verified. TMEM45A expression was markedly higher in GC tissue than in normal tissue. GC patients with TMEM45A overexpression had a poor prognosis. The AUC value of 5-year survival on the ROC curve was 0.705, indicating that TMEM45A is a reliable prognostic factor and can be used as a clinicopathological indicator alone to predict patient prognosis. Three high-risk immunomodulatory genes (CXCR4 and TGFB1) and one low-risk immunomodulatory gene (PDCD1) were obtained using both univariate and multivariate COX methods. These three immunomodulatory molecules were used to construct prognostic models. GC patients with TMEM45A overexpression have a poor prognosis and are associated with immune cell infiltration. Hence, TMEM45A is a fairly reliable independent prognostic marker.

Tumor deposits in thyroid carcinomas.

Tumor deposits (TDs) are defined as discontinuous neoplastic masses within the lymphatic drainage pathway of the primary tumor. The poor prognostic implication of these masses have been demonstrated in various cancers. The aim of this study is to investigate the incidence of TDs in our thyroid carcinoma cases, which has not been studied so far to the best of our knowledge, and to determine the prognostic value of their existence. In this retrospective cohort study, 194 thyroid carcinoma cases with cervical lymph node sampling and/or dissection were reevaluated for TDs. The case series consisted of 176 thyroid papillary carcinoma (TPC) and 18 thyroid medullary carcinoma (TMC) patients. TDs were detected in 54 (27.8%) patients. TMC cases (55.6%) had significantly more TDs compared to TPCs (25.0%; P = .006). TDs were more common in women (P = .045), and in multifocal tumors (P = .017). In addition, cases with TDs had larger tumor size (P = .002), more lymphatic invasion (P = .009), extrathyroidal extension (P < .001), and distant metastasis (P < .001). The mean follow-up period of the patients was 120.1 months (range, 4-341 months). Locoregional recurrence detected in 17 patients (8.8%) was more common in TMC (33.3%) than TPC cases (6.3%; P = .002). Distant metastasis was identified in 27 patients (13.9%). Ten-year recurrence free survival (RFS) and overall survival (OS) for all patients were 89.0% and 92.4%, respectively. Mean estimated OS time for TD negative and TD positive cases were: 281.9 (±17.2), 325.6 (±6.2) and 217.6 (±27.4) months, respectively (P = .002). Sex (P = .001), tumor type (P = .002), pT classification of the tumor (P < .001), perineural invasion (P = .002) and TDs (P = .002) were significantly associated with OS. In TPC cases individually, extrathyroidal extension (P = .001) and TDs (P = .002) were significantly correlated with distant metastasis. In multivariate analysis, only tumor size was detected as an independent prognostic marker in TPC cases (P = .005). Our results demonstrate the existence of TDs in thyroid carcinoma cases, and indicate a more aggressive behavior pattern of TDs in these tumors.

Epigenetic silencing of KCTD8 promotes hepatocellular carcinoma growth by activating PI3K/AKT signaling.

Aim: The aim of current study is to explore the epigenetic changes and function ofKCTD8 in human hepatocellular carcinoma (HCC). Materials & methods: HCC cell lines and tissue samples were employed. Methylation specific PCR, flow cytometry, immunoprecipitation and xenograft mouse models were used. Results: KCTD8 was methylated in 44.83% (104/232) of HCC and its methylation may act as an independent poor prognostic marker. KCTD8 expression was regulated by DNA methylation. KCTD8 suppressed HCC cell growth both in vitro and in vivo via inhibiting PI3K/AKT pathway. Conclusion: Methylation of KCTD8 is an independent poor prognostic marker, and epigenetic silencing of KCTD8 increases the malignant tendency in HCC.

SIRT4 is associated with microvascular infiltration, immune cell infiltration, and epithelial mesenchymal transition in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. In the present study, we evaluated SIRT4 expression levels in HCC specimens and investigated the relationships between SIRT4 expression levels, clinicopathological factors, and microvascular infiltration (MVI) in HCC. The expression levels of SIRT4 in 108 HCC specimens were examined by immunohistochemical staining. MVI in HCC specimens was divided into three subtypes: M0, M1, and M2. Comprehensive bioinformatics analysis was carried out to demonstrate SIRT4's biological functions and expression-related prognostic value. The diffuse cytoplasmic expression pattern of SIRT4 was observed in all adjacent nonneoplastic liver tissues. The levels of SIRT4 were higher in HCC than in any other type of cancer and normal tissues. In addition, the expression levels of SIRT4 were significantly decreased in HCC tissues when MVI was M1 or M2 (P=0.003) but were not related to the overall clinical outcome. To explain MVI regulated by SIRT4, we also found that SIRT4 expression correlated with epithelial-mesenchymal transition (EMT) markers and CD4+ T/NK cells and downregulated cancer-associated fibroblast cells. Also, there was a significant relationship between MVI and degree of cell differentiation (P=0.003), tumor size (P<0.001), alpha fetoprotein (AFP) (P=0.001), alanine aminotransferase (ALT) (P=0.024), and γ-glutamyl transferase (γ-GT) (P=0.024). However, SIRT4 was not an independent prognostic marker of HCC. Our results demonstrated an association between SIRT4 expression levels, MVI, immune cell infiltration, and potential biological functions, including EMT in the progression of HCC.

Screening for oncogenic AF1q expression predicts disease recurrence in gastric cancer patients

AF1q associates with tumor progression and metastases upon WNT signaling. The downstream WNT target CD44 has demonstrated prognostic significance in gastric cancer (GC). This study evaluates the impact of AF1q on tumor stage and survival in GC patients. Immunohistochemical marker expression was analyzed and data were processed to correlation and survival analysis. Out of 182 GC samples, 178 (97.8%) showed moderate to high AF1q expression (p < 0.001), these samples correlated with positive lymph node stage (p = 0.036). In a subgroup analysis of patients with nodal-positive GC (n = 129, 70.9%), enhanced tumoral AF1q expression resulted in impaired recurrence-free survival (RFS, p = 0.030). Enhanced tumoral CD44 expression resulted in impaired disease-specific survival (DSS) in the subgroup of patients with nodal-positive GC (p = 0.031) as well as in the overall GC group (p = 0.005). AF1q demonstrated as an independent prognostic marker for RFS (p = 0.035) and CD44 for DSS (p = 0.036). AF1q has shown potential for prognostication of RFS in GC patients and is predominantly expressed in nodal-positive GC. Testing AF1q provides a possibility of identifying patients with locoregional (and advanced) disease, particularly at risk for disease recurrence. Implementing AF1q into the diagnostic process may facilitate screening, prognosis estimation as well as consideration of preoperative multimodal treatment in patients qualifying for elective upfront surgery.

Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.

Prognostic value of exercise longitudinal right ventricular free wall strain in patients with sickle cell disease.

Longitudinal right ventricular free wall strain (RVFWS) has been identified as an independent prognostic marker in patients with pulmonary hypertension. Little is known however about the prognostic value of RVFWS in patients with sickle cell (SC) disease, particularly during exercise. We therefore examined the prognostic significance of RVFWS both at rest and with exercise in patients with SC disease and normal resting systolic pulmonary artery pressure (SPAP). Consecutive patients with SC disease referred for bicycle ergometer stress echocardiography (SE) were enrolled ftom July 2019 to January 2021. All patients had measurable tricuspid regurgitation velocity (TRV). Conventional echocardiography parameters, left ventricular global longitudinal strain (LVGLS), RVFWS, and ventriculoarterial coupling indices (TAPSE/SPAP and RVFWS/SPAP) were assessed at rest and peak exercise. Repeat SE was performed at a median follow-up of 2years. The cohort consisted of 87 patients (mean age was 31 ± 11years, 66% females). All patients had normal resting TRV < 2.8m/s, RVFWS and LVGLS at baseline. There were 23 (26%) patients who had peak stress RVFWS < 20%. They had higher resting and peak stressTRV andSPAP, but lower resting and peak stressTAPSE/SPAP, RVFWS/SPAP, and LVGLS as well as lower peak stresscardiac output when compared to patients with peak stressRVFWS ≥ 20% (p < 0.05). Patients with baseline peak stressRVFWS < 20% had a significant decrease in exercise performance at follow-up (7.5 ± 2.7min at baseline vs. 5.5 ± 2.8min at follow-up, p < 0.001). In the multivariate analysis, baseline peak stressRVFWS was the only independent predictor of poorer exercise performance at follow-up [odds ratio 8.2 (1.2, 56.0), p = 0.033]. Among patients with SC disease who underwent bicycle ergometer SE, a decreased baseline value of RVFWS at peak stress predicted poorer exercise time at follow-up.

Membrane Palmitoylated Protein 2 Serves as a Potential Biomarker for Colon Adenocarcinoma through Promoting CGAS-STING Pathway

This research investigated the role of Membrane Palmitoylated Protein 2 (MPP2) in colon adenocarcinoma (COAD), the third most prevalent form of colorectal cancer. Utilizing TCGA, GEPIA, and HPA datasets alongside Western blotting, we examined MPP2 expression in normal versus cancerous tissue. Kaplan-Meier plots from GEPIA indicated lower MPP2 levels in COAD patients correlating with worse overall survival (P &lt; 0.05). Moreover, MPP2 was identified as a distinct prognostic indicator for COAD and significantly associated with clinicopathological features (P &lt; 0.05), assessed via chi-square tests and Cox regression models. We further explored MPP2’s link to COAD immune cells using Cibersort, revealing its correlation with the infiltration of 8 immune cells (P &lt; 0.05). In vivo and in vitro experiments demonstrated that elevated MPP2 levels might enhance cell proliferation and migration while suppressing apoptosis. Applying Gene Set Enrichment Analysis (GSEA), we predicted MPP2’s involvement in tumor progression via the DNA sensing pathway, a finding supported by cellular studies. In summary, COAD patients exhibit decreased MPP2 expression, which inversely correlates with prognosis. MPP2 appears to influence immunosuppression and tumor progression through various mechanisms, suggesting its potential as an independent prognostic marker in COAD. Further investigation into MPP2’s implications is warranted.

Survival Outcomes and Prognostic Factors in Therapy-Related Acute Myeloid Leukemia: A SEER Database Study, 2000-2020

IntroductionWith advances in therapeutics and longer survival across different cancer spectrums, the incidence of therapy-related acute myeloid leukemia (tAML) has continued to rise. This study aims to evaluate the trend of survival outcomes and their association with sociodemographic factors in tAML over the last 20 years. MethodsWe identified tAML patients between 2000 and 2020 from the Surveillance, Epidemiology, and End Results database. Patients were divided into 4 age groups: 18-39, 40-59, 60-69, and >= 70 years, and 4 diagnostic periods: 2000-2005, 2006-2010, 2011-2015, and 2016-2020. Overall survival (OS) was compared using Kaplan Meier and log-rank methods. ResultsThe 1-year (and 5-year) OS in patients with tAML was 59.3% (33.7%), 48.2% (24.8%), 37.2% (11.1%), and 32.9% (5.5%) in age groups 18-39, 40-59, 60-69, and >=70 years, respectively. The 1-year (and 5-year) OS based on the year of diagnosis was 20.9% (13.2%), 36.8% (15.2%), 41.9% (13.88%), and 40.4% (not reached) for 2000-2005, 2006-2010, 2011-2015, and 2016-2020 respectively. Among the youngest cohort aged 18-39 years, 1-year OS was 35.7%, 57.7%, 66.7%, and 59.6%, respectively, in 4 diagnostic periods, whereas 1-year OS was 10.5%, 23.9%, 32.2%, and 36.9%, respectively, in the oldest cohort aged >=70 years. Age, year of diagnosis, and geographic location were independent prognostic markers of OS. ConclusionOur study demonstrates a significant improvement in the 1-year OS of tAML patients over the last decade, but the long-term prognosis remains dismal. Older patients continue to show improved survival in recent years with the addition of newer intensive and nonintensive options.

Analysis of methylation-driven genes for predicting the prognosis of patients with oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy that is characterized by early distant metastasis and poor prognosis. DNA methylation plays an important role in the etiology and pathogenesis of OSCC. This study aimed to identify methylation-driven genes through bioinformatics analysis as potential biomarkers for early diagnosis and prognostic assessment of OSCC. Methylation data, RNA sequencing (RNA-seq) data and clinical prognosis information of OSCC patients were retrieved from The Cancer Genome Atlas (TCGA) database. The R packages MethylMix were employed to analyze the correlation between methylation status and corresponding gene expression in tumor and normal tissues to obtain methylation-driven genes. Univariate Cox regression analysis was developed to further screen methylation-driven genes associated with the prognosis of OSCC patients. Subsequently, multivariate Cox regression analysis was utilized to construct a linear prognostic risk prediction model. Furthermore, a combined survival analysis integrating methylation and gene expression was performed to investigate the prognostic value. A total of 374 differentially expressed methylation-driven genes were identified. Seven methylation-driven genes (BST2, KRT15, ZNF134, NT5E, GSTA7P, NAPRT, and GOLPH3L) were found to be significantly associated with patient prognosis. Additionally, four methylation-driven genes (BST2, KRT15, ZNF134 and NAPRT) were used to construct a linear prognostic risk prediction model for OSCC patients. Furthermore, a combined Kaplan-Meier survival analysis revealed that three methylation-driven genes (ZKSCAN7, MFF, ZNF134) alone can be used as independent prognostic markers or drug targets. Our findings facilitate a better understanding of molecular mechanisms of OSCC and provide potential biomarkers of early diagnosis, precision treatment and prognosis evaluation.

Ki-67 AS A PREDICTING FACTOR OF NASOPHARYNGEAL, BREAST, AND CERVICAL CANCER: A LITERATURE REVIEW

Background: Although the exact role remains unknown, Ki-67 is vital in cell division. Ki-67 is a nuclear nonhistone protein present in all active phases of the cell cycle. It has the potential to predict the prognosis of responsiveness to radiotherapy, chemotherapy, or endocrine therapy, estimate residual risk, and predict recurrence in many types of cancer, including nasopharyngeal cancer (NPC), breast cancer (BC), and cervical cancer (CX), and be a marker for treatment efficacy. We want to review the efficacy of Ki-67 as a predicting factor for three types of cancer, including NPC, breast, and cervical cancer, from several pieces of literature. Materials and Methods: We are conducting a literature review to describe the role of Ki-67 as a predicting factor in NPC, BC, and CX. Results: Pretreatment Ki-67 is used as an independent prognostic marker in NPC, and elevated values are associated with poor prognosis. High Ki-67 expression may indicate poorer recurrence-free survival and overall survival. A high Ki-67 index significantly correlated with adverse prognostic factors. Conclusion: A high expression of Ki-67 in NPC, breast cancer, and cervical cancer is associated with poor prognosis, poorer recurrence, and overall survival rates. Ki-67 can be considered as a valuable biomarker of many cancers. Keywords: Radiotherapy, Ki-67, nasopharyngeal cancer, breast cancer, cervical cancer

Epigenetic silencing of BEND4, a novel DNA damage repair gene, is a synthetic lethal marker for ATM inhibitor in pancreatic cancer.

Synthetic lethality is a novel model for cancer therapy. To understand the function and mechanism of BEN domain-containing protein 4 (BEND4) in pancreatic cancer, eight cell lines and a total of 492 cases of pancreatic neoplasia samples were included in this study. Methylation-specific polymerase chain reaction, CRISPR/Cas9, immunoprecipitation assay, comet assay, and xenograft mouse model were used. BEND4 is a new member of the BEN domain family. The expression of BEND4 is regulated by promoter region methylation. It is methylated in 58.1% (176/303) of pancreatic ductal adenocarcinoma (PDAC), 33.3% (14/42) of intraductal papillary mucinous neoplasm, 31.0% (13/42) of pancreatic neuroendocrine tumor, 14.3% (3/21) of mucinous cystic neoplasm, 4.3% (2/47) of solid pseudopapillary neoplasm, and 2.7% (1/37) of serous cystic neoplasm. BEND4 methylation is significantly associated with late-onset PDAC (> 50 years, P < 0.01) and tumor differentiation (P < 0.0001), and methylation of BEND4 is an independent poor prognostic marker (P < 0.01) in PDAC. Furthermore, BEND4 plays tumor-suppressive roles in vitro and in vivo. Mechanistically, BEND4 involves non-homologous end joining signaling by interacting with Ku80 and promotes DNA damage repair. Loss of BEND4 increased the sensitivity of PDAC cells to ATM inhibitor. Collectively, the present study revealed an uncharacterized tumor suppressor BEND4 and indicated that methylation of BEND4 may serve as a potential synthetic lethal marker for ATM inhibitor in PDAC treatment.

Prognostic Role of Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma

BackgroundIn oral squamous cell carcinoma (OSCC), the tumor-node-metastasis (TNM) staging system is a significant factor that influences prognosis and treatment decisions for OSCC patients. Unfortunately, TNM staging does not consistently predict patient prognosis and patients with identical clinicopathological characteristics may have vastly different survival outcomes. Host immunity plays an important role in tumor progression but is not included in the TNM staging system. Tumor-infiltrating lymphocytes (TILs) are part of the host immune response that recognizes tumor cells; and the presence of TILs has emerged as potential candidates for prognostic markers for many types of cancers. The present study aims to determine the association of T cell-specific markers (CD3, CD4, CD8, and FOXP3) with clinicopathological characteristics and survival outcomes in OSCC patients. The prognostic value of CD3, CD4, and CD8 will also be evaluated based on tumor stage.MethodsTissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced).ResultsCD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients.ConclusionsTIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients.