The clinicopathological significance and prognostic value of PD-L1 in oral squamous cell carcinoma.

OBJECTIVE: To investigate the relationship between the expression of PD-L1 in OSCC and the clinicopathological features and prognosis of patients. METHODS: We retrospectively analyzed the clinicopathological data and prognosis of 381 OSCC patients. Immunohistochemical staining was performed on OSCC tumor specimens, and the expression level of PD-L1 was evaluated according to the combined positive score (CPS). Kaplan-Meier analysis was used to identify the effect of PD-L1 expression and clinicopathological features on the prognosis of patients. Univariate and multivariate Cox regression analyses were conducted to determine the hazard factors affecting the prognosis of patients. RESULTS: PD-L1 overexpression was significantly associated with cervical lymph node metastasis (p = 0.018), worse clinical stage (p = 0.022), worse tumor differentiation (p = 0.046), and worse depth of invasion (DOI) (p = 0.003). Poorer clinical stage and degree of tumor differentiation were significantly associated with poorer OS and DSS in patients. PD-L1 expression was not associated with prognosis in patients with OSCC. CONCLUSIONS: High PD-L1 expression was significantly associated with higher tumor malignancy in OSCC patients. Poorer clinical stage and degree of tumor differentiation were associated with poor prognosis in OSCC patients. Our results may help clinicians develop more appropriate individualized treatment strategies for their patients, thus improving their outcomes.

Network Pharmacology to Reveal the Mechanism of Fufang Banmao Capsule for Treating Unresectable Primary Liver Cancer and Clinical Data Validation.

INTRODUCTION: Fufang Banmao capsules (FFBM), a traditional Chinese medicine, has been used to treat primary liver cancer (PLC) for several years. However, the bioactive ingredients, and mechanism of FFBM for treating PLC remains unclear. Our objective is to utilize network pharmacology to investigate these aspects and subsequently validate their effectiveness through clinical data. MATERIALS AND METHODS: The FFBM ingredients were obtained from the HERB database and screened for bioactive ingredients using the SwissTargetPrediction database. The PharmMapper and GEO database were used to acquire targets and differentially expressed genes (DEGs) for FFBM and PLC, respectively. Common targets were identified using Venn diagrams, followed by enrichment and protein-protein interaction (PPI) analysis. Furthermore, the Cytoscape software was utilized to identify Hub genes and construct the ingredienttarget- pathway network. Subsequently, patients diagnosed with unresectable PLC who underwent transcatheter arterial chemoembolization (TACE) at our hospital between January 2008 and December 2019 were retrospectively collected. Finally, Cox analysis was conducted to reveal the role of FFBM in the treatment of unresectable PLC. RESULTS: FFBM had 232 targets, and PLC had 1582 DEGs. HSP90AA1 and SRC were identified as crucial targets. Alpha-santalol, glycyrrhizin, and morroniside were identified as the top three bioactive ingredients. Enrichment analysis revealed a significant connection between FFBM utilization for treating PLC and multiple pathways, such as chemical carcinogenesis, PI3K-AKT, Rap1, FoxO, MAPK, and VEGF pathway. Clinic data revealed that consuming FFBM significantly improved the prognosis of unresectable PLC with a hazard ratio of 0.69. CONCLUSION: Our study identified the bioactive ingredients of FFBM and its potential mechanisms for treating PLC. Additionally, we validated the effectiveness through clinical data.

Prognostic value of right atrial function in patients with significant tricuspid regurgitation.

AIMS: Although right ventricular (RV) dysfunction is associated with adverse outcomes in tricuspid regurgitation (TR), the potential role of right atrial (RA) function is unknown. We aimed to investigate the relationship between RA function and clinical outcomes in patients with significant TR. METHODS: This retrospective study included 169 outpatients with moderate or severe TR due to left-sided heart diseases who underwent transthoracic echocardiography between June 2020 and April 2023 (average age, 75 ± 10 years; male, 40%). Patients with atrial fibrillation were excluded from this study due to the inaccuracy of the evaluation using 2D speckle-tracking echocardiography. RA function was compared between patients with and without events, which were defined as all-cause mortality or hospitalization due to heart failure. RA function was calculated as RA global longitudinal strain (RAGLS) with the 2D speckle-tracking echocardiography. RESULTS: During a median follow-up of 13 months, 19 patients had events (all-cause mortality: 14 cases, hospitalization due to heart failure: 5 cases). RAGLS was lower in patients with events than in those without events (13% ± 10% vs. 18% ± 9%, P = 0.02). When the patients were categorized into two groups [low RAGLS ≤ 16.2% vs. high RAGLS > 16.2%, high RA volume index (RAVI) ≥ 50 mL/m2 vs. low RAVI < 50 mL/m2], Kaplan-Meier curves showed that patients with low RAGLS had higher event rates than those with high RAGLS (log-rank test, P = 0.003). Patients with high RAVI had higher event rates than those with low RAVI (log-rank test, P < 0.001). In the multivariate Cox regression analysis, low RAGLS (≤16.2%) was significantly associated with events in a model that included RV dysfunction (RV fractional area change ≤ 35%) or high RAVI (≥50 mL/m2) (hazard ratio: 4.55, 95% confidence interval: 1.51-13.71, P < 0.01; hazard ratio: 4.57, 95% confidence interval: 1.52-13.79, P < 0.01, respectively). CONCLUSIONS: RAGLS is associated with all-cause mortality and hospitalization due to heart failure in patients with significant TR. Our results suggest that RA function is a sensitive marker for identifying the risk stratification of significant TR.

Comparison of two platinum-containing chemotherapy regimens in the treatment of advanced cervical cancer with concurrent chemoradiotherapy.

OBJECTIVE: The present study aims to compare the efficacy and side effects of a platinum-containing combination regimen and platinum single-drug concurrent chemoradiotherapy (CCRT) in patients with advanced cervical cancer (CC) and to understand the prognostic factors in patients with CC. METHODS: A total of 108 cases of CC treated in Wenzhou Central Hospital were retrospectively selected. Patients in the monotherapy (single-drug) group received external pelvic radiotherapy (RT) and platinum-based single-drug chemotherapy (CT). Patients in the combined group received external pelvic RT and platinum-containing CT. The efficacy, CCRT time, 3-year survival rate after treatment and side effects were compared between the two groups, and the prognostic factors were analysed. RESULTS: The total effective rate was 74.07% in the monotherapy group and 72.22% in the combined group (p = .828). The incidences of myelosuppression, gastrointestinal reaction and abnormal liver function in the grades III-IV combined group were significantly higher than those in the monotherapy group (p < .001; p = .236; p = .022). Furthermore, the CCRT time was significantly longer in the combined group than in the monotherapy group, and the 3-year overall survival (OS) was 81.48% in the monotherapy group and 79.63% in the combined group (p = .643; p = .808). The older the age was, the higher the serum squamous cell carcinoma antigen (SCC-Ag) value before treatment and the shorter the progression-free survival time. In addition, the older the adenocarcinoma (AC) was, the shorter the OS. CONCLUSION: The efficacy of the two regimens in the treatment of advanced CC was similar. However, the side effects increased significantly during combined treatment. PROGNOSTIC FACTORS: A higher patient age, having an AC and stage of IIIa and a high SCC-Ag value before treatment resulted in a relatively low survival rate.

Tertiary lymphoid structures as potential biomarkers for cancer prediction and prognosis.

Tertiary lymphoid structures (TLSs) are ectopic lymphocyte aggregates formed in non-lymphoid tissues, including cancers, and are loci for the generation of in situ anti-tumor immune responses, which play a crucial role in cancer control. The state of TLS presence in cancer and its composition can significantly impact the treatment response and prognosis of patients. TLSs have the potential to serve as predictive and prognostic biomarkers for cancer. However, the mechanisms underlying TLS formation in cancer and how the essential components of TLSs affect cancer are not fully understood. In this review, we summarized TLS formation in cancer, the value of the TLS in different states of existence, and its key constituents for cancer prediction and prognosis. Finally, we discussed the impact of cancer treatment on TLSs.

Whole-exome sequencing of vulvar squamous cell carcinomas reveals an impaired prognosis in patients with TP53 mutations and concurrent CCND1 gains.

Very little information is available on the mutational landscape of vulvar squamous cell carcinoma (VSCC), a disease that mainly affects older women. Studies focusing on the mutational patterns of the currently recognized etiopathogenic types of this tumor [human papillomavirus (HPV)-associated (HPV-A), HPV-independent (HPV-I) with TP53 mutation (HPV-I/TP53mut), and HPV-I with wild-type TP53 (HPV-I/TP53wt]) are particularly rare, and there is almost no information on the prognostic implications of these abnormalities. Whole-exome DNA sequencing of 60 VSCC and matched normal tissues from each patient was performed. HPV detection, immunohistochemistry (IHC) for p16, p53, and mismatch repair proteins were also performed. Ten tumors (16.7%) were classified as HPV-A, 37 (61.7%) as HPV-I/TP53mut, and 13 (21.6%) as HPV-I/TP53wt. TP53 was the most frequently mutated gene (66.7%), followed by FAT1 (28.3%), CDKN2A (25.0%), RNF213 (23.3%), NFE2L2 (20%) and PIK3CA (20%). All the 60 tumors (100%) were DNA mismatch repair proficient. Seventeen tumors (28.3%) showed CCND1 gain. Bivariate analysis, adjusted for FIGO stage, revealed that TP53 mutation, CCND1 gain, and the combination of the two alterations were strongly associated with impaired recurrence-free survival (hazard ratio=4.4, p<0.001) and disease-specific survival (hazard ratio=6.1, p=0.002). Similar results were obtained when p53 IHC status was used instead of TP53 status and when considering only HPV-I VSCC. However, in the latter category, p53 IHC maintained its prognostic impact only in combination with CCND1 gains. All tumors carried at least one potentially actionable genomic alteration. In conclusion, VSCCs with CCND1 gain represent a prognostically adverse category among HPV-I/TP53mut tumors. All patients with VSCCs are potential candidates for targeted therapy.

Rationale and design of the French Observatory of Acute Heart Failure (OFICA2).

BACKGROUND: Acute heart failure (AHF) is a leading cause of hospitalization and mortality - especially in patients aged≥65 years in high-income countries - and represents a high healthcare burden. In the past decade, the epidemiology and management of heart failure (HF) has changed, with the emergence of new medical and interventional therapeutics, but up-to-date real-life data are scarce. AIMS: The main objectives are to describe baseline characteristics (with an emphasis on lifestyle, cognitive status, HF knowledge and treatment adherence), management, and in-hospital and mid-term outcomes of AHF patients in France. Secondary objectives are to investigate determinants of prognosis, modalities of treatment and follow-up, and identify gaps between guidelines and real-life management. METHODS: OFICA2 is a prospective multicentre observational survey that enrolled 1513 patients hospitalized for AHF in 80 participating centres in France during March and April 2021. The diagnosis of AHF was made according to the European Society of Cardiology guidelines definition. Inclusion criteria were age≥18years, health coverage and consent to participate. Detailed information was collected prospectively starting at admission. Thanks to direct linking with the French National Health Database, the anteriority up to 2years before inclusion, as well as a 3-year follow-up is specified for each patient and includes individual information on death, hospital admissions, major clinical events, drug delivery and use of reimbursed health resources. CONCLUSION: This cohort provides a representative snapshot on contemporary AHF, with a particular focus on self-care determinants, and will improve knowledge about AHF presentation, management and outcomes.

Prognostic and predictive value of tertiary lymphoid structures in TURBT materials: Should it be seated in the routine pathological examination, and can it be used in deciding on the treatment method?

OBJECTIVE: This study aims to reveal the importance of tertiary lymphoid structures (TLS) in transurethral resection of bladder tumor (TURBT) materials with a practical and applicable method in which the effect of a certain threshold value on survival and treatment response can be implicated. METHODS: TURBT materials that had not previously received any treatment (chemotherapy, radiotherapy, or immunotherapy) and were diagnosed for the first time at Mardin Training and Research Hospital between 2014 and 2022 were included in the study. The maximum TLS per 4× magnification field (field diameter: 4.5 mm) was recorded. Grouping and statistical analysis of the TLS number were performed using threshold values of "≥1", "≥2", and "≥3". RESULTS: TLSs were more frequently found in high-grade tumors (P = 0.008) and showed a strong association with stage progression (P < 0.001). It was also significantly associated with many adverse histopathological parameters. Conversely, high TLS (≥1, ≥2, and ≥3) appeared to be associated with fewer recurrences (P = 0.032, P = 0.001, and P = 0.018, respectively), and cases with higher TLS showed longer recurrence-free survival (P = 0.089, P = 0.023, P = 0.037, respectively). TLS≥3 was found to be an independent parameter that was associated with favorable RFS (P = 0.019, HR = 0.401), and multifocality was found to be an independent risk factor for RFS (P = 0.023, HR = 2.302). CONCLUSION: This study is the first to demonstrate the relationship between the presence and specific thresholds of TLS in TURBT materials with prognostic parameters. Including this information in the routine pathological examination of TURBT materials will allow a more accurate approach to treatment and follow-up, especially in patients with non-muscle invasive bladder cancer (NMIBC).

Whether unplanned excision on synovial sarcoma will influence the prognosis? An retrospective analysis of prognostic factors in 54 synovial sarcoma cases at a single center.

OBJECTIVE: In this study, we examined the reason and prognosis of unplanned excision on synovial sarcoma. METHODS: We retrospectively analyzed 54 patients diagnosed with synovial sarcoma between March 2013 and February 2021, including 26 cases of unplanned excision surgery. Patients were divided into two groups based on whether they underwent unplanned excision. Then, factors such as gender, age, tumor size, tumor location, American Joint Committee on Cancer (AJCC) staging, unplanned excision, time of onset, duration of disease, radiotherapy, chemotherapy, amputation, local recurrence factors, and death were statistically evaluated. RESULTS: The results of a multivariate analysis revealed that the AJCC staging is an independent factor for patient prognosis. When patients were divided into two groups, those who had undergone unplanned excision and those who had not, statistical analysis revealed that there was no difference of survival between two groups, but tumor size and AJCC staging had statistical difference. To further explore the influences of unplanned excision, we performed propensity score analysis with 1:1 matching using the nearest neighbor matching method to balance the covariates between the two groups. There was no difference of survival between two groups after propensity score matching. CONCLUSION: Unplanned excision is commonly performed in synovial sarcoma and do not impact the prognosis after extensive resection.

Single-cell transcriptomic sequencing analysis of mechanistic insights into the IFN-γ signaling pathway in different tumor cells.

PURPOSE: This study aimed to investigate the relationship between the interferon-gamma (IFN-γ) pathway in different tumor microenvironments (TME) and patients' prognosis, as well as the regulatory mechanisms of this pathway in tumor cells. METHODS: Using RNA-seq data from the TCGA database, we analyzed the predictive value of the IFN-γ pathway across various tumors. We employed a univariate Cox regression model to assess the prognostic significance of IFN-γ signaling in different tumor types. Additionally, we analyzed single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database to examine the distribution characteristics of the IFN-γ pathway and explore its regulatory mechanisms, highlighting how IFN-γ influenced cellular interactions within the TME. RESULTS: Our analysis revealed a significant association between the IFN-γ pathway and adverse prognosis in pan-cancer tissues (P < 0.001). Interestingly, this correlation varied regarding positive and negative regulation across different tumor types. Through a detailed examination of scRNA-seq data, we found that the IFN-γ pathway exerted substantial regulatory effects on stromal and immune cells. In contrast, its expression and regulatory patterns in tumor cells exhibited diversity and heterogeneity. Further analysis indicated that the IFN-γ pathway not only enhanced the immunogenicity of tumor cells but also inhibited their proliferation. Cell-cell interaction analysis confirmed the pivotal role of the IFN-γ pathway within the overall regulatory network. Moreover, we identified HMGB2 (high mobility group box 2) in T cells as a potential key regulator of tumor cell proliferation. CONCLUSIONS: The IFN-γ pathway exhibited a dual function by both suppressing tumor cell proliferation and enhancing their immunogenicity, positioning it as a pivotal target for refined cancer diagnosis and cancer strategies.

Low Absolute Lymphocyte Count Correlates with Lymph Node Metastases and Worse Survival of Patients with Gastric Cancer.

BACKGROUND: Several studies have found that the absolute lymphocyte (ALC) or neutrophil count predicts the survival of patients with solid tumors, and that the neutrophil-to-lymphocyte ratio and the prognostic nutritional index are useful markers of gastric cancer prognosis. However, it remains unclear whether the ALC is prognostic of lymph node (LN) metastasis in patients with gastric cancer. In this study, we aimed to explore the impact of ALC on prognosis and distinctive clinical characteristics in patients with gastric cancer. PATIENTS AND METHODS: The medical records of patients with gastric adenocarcinomas who underwent radical gastrectomy with curative intent at Seoul St. Mary's Hospital and Yeouido St. Mary's Hospital between January 2010 and December 2017 were reviewed. Of these, 4149 patients for whom preoperative white blood cell, neutrophil, and lymphocyte counts were available were enrolled. RESULTS: In all 4149 patients, ALC gradually decreased as the pN stage increased. Those with an ALC of less than 1360 cells/µL were defined as a low-ALC group, and advanced cT and cN stages were the strongest risk factors for LN metastasis in both univariate and multivariate analyses; undifferentiated tumor histology and a low ALC were also significant risk factors. Patients of all stages in the ALC-low group exhibited poorer prognoses. The ALC-low group also exhibited a higher recurrence rate in a greater proportion of LNs. CONCLUSIONS: In patients with gastric cancer, as the preoperative ALC decreases, the incidence of LN metastasis increases. A low ALC is associated with a high recurrence rate, particularly in LNs.

Clinical significance of chronic pulmonary aspergillosis in lung cancer patients undergoing anticancer drug therapy.

BACKGROUND: Advances in anticancer drugs for lung cancer (LC) have improved the prognosis of LC. Chronic pulmonary aspergillosis (CPA) is a progressive and often exacerbating respiratory disease with a poor prognosis. To date, the prognosis of LC complicated by CPA has not been elucidated. This study investigated the clinical implications of concomitant CPA in patients with LC undergoing anticancer drug treatment. METHODS: Between January 2010 and May 2020, we consecutively enrolled patients with LC complicated with CPA at five different institutions in Japan. We analyzed patients with LC complicated by CPA who received anticancer drug treatment. RESULTS: A total of 10 patients with LC complicated by CPA received anticancer drug treatment. The median overall survival (OS) was 14.57 months (95% confidence interval [CI]: 5.37-21.67). The cause of death in all patients was LC. Six of the seven patients with LC did not show worsening pulmonary aspergillosis lesions during the anticancer drug treatment. Although two patients discontinued anticancer drug treatment due to pneumonitis, CPA complications did not interfere with the continuation of anticancer drug treatment. In univariate analyses, squamous histology (p = 0.01) and body mass index (<18.5 kg/m2) (p = 0.0008) were significantly associated with poorer OS. CONCLUSIONS: This study demonstrated that the cause of death in LC patients with concomitant CPA who received anticancer drug treatments and effective antifungal treatment was LC progression. Further large-scale studies are needed to identify the effect of CPA in patients with LC.

Blood Neutrophil-to-Lymphocyte Ratio as a Potential Prognostic Marker in Dogs ≤10 kg With Multicentric Lymphoma.

Canine lymphoma, the most prevalent haematopoietic tumour in dogs, presents significant challenges in veterinary oncology. This study investigates the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in small-sized dogs (≤10 kg) with multicentric lymphoma. In this retrospective study, we examined medical records and haematological data from 35 dogs to assess the association between NLR and two key outcomes: time-to-progression (TTP) and lymphoma-specific survival (LSS) using Cox proportional hazards models. Our findings revealed a significant correlation between elevated NLR and a worse prognosis, as evidenced by TTP (p = 0.005) and LSS (p = 0.001). NLR is linked to increased hazard ratios (HRs) for the time-to-progression rate (TTPR) at 180, 360 and 540 days (p = 0.001, p = 0.003 and p = 0.005, respectively) and the lymphoma-specific survival rate (LSSR) at the same intervals (p = 0.016, p = 0.001 and p = 0.001, respectively). Cutoff value of 3.764 for NLR was established, above which there is a significantly increased risk of early disease progression and decreased survival. Additionally, our analysis indicates that dogs with substage b exhibited earlier progression than those with substage a, evident in overall (p = 0.026) and TTPR at 180 days (p = 0.004), 360 days (p = 0.018), 540 days (p = 0.026) and LSSR at 180 days (p = 0.033). The results underscore the potential of NLR as a prognostic marker in cases of dogs ≤10 kg with multicentric lymphoma, suggesting that higher NLR is associated with a poorer prognosis.

Clinical significance of glomerular IgM deposit in IgA nephropathy: a 5-year follow-up study.

The significance of glomerular IgM deposit intensity in IgA Nephropathy (IgAN) remained ambiguous and requires further research. Patients with biopsy-proven IgAN in our hospital from January 2018 to May 2023 were recruited into this retrospective single-center study. Patients who presented with positive IgM deposit were included in IgM + cohort while patients with negative IgM deposit were included in IgM- cohort. Of the IgM+, patients whose IF intensity of IgM deposits exceeded 1+ formed IgM-H cohort while patients whose IF intensity of IgM deposits was equal to 1+ consisted IgM-L cohort. Pairwise comparisons were performed among these cohorts to determine clinical disparities, following the propensity score matching process. Among 982 IgAN patients, 539 patients presented with positive IgM deposit. The Kaplan-Meier analysis showed that the IgM deposit did not contribute adversely to the outcomes (eGFR decreased from the baseline ≥ 50% continuously or reached end-stage renal disease). However, the Cox regression analysis showed that increased intensity of IgM deposit was an independent risk factor (p = 0.03) in IgM+. The IgM-H exhibited more pronounced segmental glomerulosclerosis (p = 0.02) than the IgM-L, which may also be associated more directly with higher urine protein levels (p = 0.02). Moreover, our generalized linear mixed model demonstrated a remarkably higher urine albumin/creatinine ratio (p < 0.01) and serum creatinine (p = 0.04) levels as well as lower serum albumin (p < 0.01) level in IgM-H persistently during the 5-year follow-up. This study concluded that increased intensity of glomerular IgM deposits may contribute adversely to clinicopathologic presentation and outcome in those IgM + patients.

Lipid profile and mortality in patients with pulmonary thromboembolism; a systematic review and meta-analysis.

INTRODUCTION: Acute pulmonary thromboembolism (PTE) is a life-threatening disease. Considering the availability and accessibility of assessing the serum lipids, this study aims to define the predictive value of lipid profile, as well as the history of lipid disorders, for the mortality of PTE patients. CONTENT: Clinical studies, in which the relation of lipid profile, including triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol, as well as history of imbalance of lipids, with mortality of PTE patients was reported, were included. Non-English articles, reviews, letters, editorials, and non-English papers were excluded. A systematic search was conducted in PubMed, Embase, Scopus, and Web of Science databases. The risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal tools and CMA 4 was utilized for the quantitative synthesis. Out of 3,724 records, six studies were included in this systematic review. Lipid profile is suggested as a prognostic marker for survival in patients with PTE so higher initial serum HDL, LDL, and total cholesterol levels were associated with lower mortality rates in PTE patients. In addition, dyslipidemia was found to be associated with mortality of PTE patients. Based on the quantitative synthesis, there was a greater serum level of HDL in the survival group (standardized mean difference: -0.98; 95 % CI: -1.22 to -0.75; p-value<0.01). SUMMARY AND OUTLOOK: Mortality is lower in PTE patients with greater serum lipid levels; therefore, the early prognosis of PTE may be ascertained by measuring serum lipids within the first 24 h of admission.

Integrative single-cell analysis of longitudinal t(8;21) AML reveals heterogeneous immune cell infiltration and prognostic signatures.

Introduction: Immunotherapies targeting T cells in solid cancers are revolutionizing clinical treatment. Novel immunotherapies have had extremely limited benefit for acute myeloid leukemia (AML). Here, we characterized the immune microenvironment of t(8;21) AML patients to determine how immune cell infiltration status influenced prognosis. Methods: Through multi-omics studies of primary and longitudinal t(8;21) AML samples, we characterized the heterogeneous immune cell infiltration in the tumor microenvironment and their immune checkpoint gene expression. Further external cohorts were also included in this research. Results: CD8+ T cells were enriched and HAVCR2 and TIGIT were upregulated in the CD34+CD117dim%-High group; these features are known to be associated with immune exhaustion. Data integration analysis of single-cell dynamics revealed that a subset of T cells (cluster_2) (highly expressing GZMB, NKG7, PRF1 and GNLY) evolved and expanded markedly in the drug-resistant stage after relapse. External cohort analysis confirmed that the cluster_2 T-cell signature could be utilized to stratify patients by overall survival outcome. Discussion: In conclusion, we discovered a distinct T-cell signature by scRNA-seq that was correlated with disease progression and drug resistance. Our research provides a novel system for classifying patients based on their immune microenvironment.

Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer invasiveness by activation of target of rapamycin kinase/autophagy signaling.

BACKGROUND: Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers. AIM: To investigate the role of MOB3B in colorectal cancer (CRC). METHODS: This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results. RESULTS: MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts. CONCLUSION: Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

Clinicopathologic Factors Associated with Prognosis in Patients with Metastatic Squamous Cell Carcinoma of the Anal Canal: A Multicenter Cohort Study.

Objectives: Due to its rarity, there is insufficient evidence for managing ASCC patients with distant metastasis. Thus far, the therapeutic strategy for distant metastasis of ASCC is less standardized and requires a more individualized approach. Therefore, it is crucial to obtain information regarding treatment outcomes and prognostic factors following the development of distant metastasis to identify optimal care strategies for better patient outcomes and predict their prognosis. Methods: In the multi-institute cohort study conducted in Japan, we retrospectively assessed 58 ASCC patients with synchronous distant metastasis and 28 ASCC patients with metachronous distant metastasis. Results: When comparing the OS between ASCC patients with synchronous distant metastasis and metachronous distant metastasis, there was no statistically significant difference between the two groups. The OS rate at five years was 37.4% for patients with synchronous distant metastasis and 27.6%; for metachronous distant metastasis. In ASCC patients with synchronous distant metastasis, patients with distant metastasis at multiple sites exhibited extremely worse OS than those at single sites (HR: 4.56, 95% CI: 1.16-18.00, P< 0.0001). In addition, in ASCC patients with metachronous distant metastasis, early recurrence was an independent factor for predicting poor OS in the multivariate analysis (HR: 4.13, 95% CI: 1.22-13.94, P = 0.022). Conclusions: ASCC patients with distant metastasis at multiple sites were a worse prognosis. In addition, early recurrence was identified as an independent prognostic factor for OS among ASCC patients.

Enhancing prognostic prediction in hepatocellular carcinoma post-TACE: a machine learning approach integrating radiomics and clinical features.

Objective: This study aimed to investigate the use of radiomics features and clinical information by four machine learning algorithms for predicting the prognosis of patients with hepatocellular carcinoma (HCC) who have been treated with transarterial chemoembolization (TACE). Methods: A total of 105 patients with HCC treated with TACE from 2002 to 2012 were enrolled retrospectively and randomly divided into two cohorts for training (n = 74) and validation (n = 31) according to a ratio of 7:3. The Spearman rank, random forest, and univariate Cox regression were used to select the optimal radiomics features. Univariate Cox regression was used to select clinical features. Four machine learning algorithms were used to develop the models: random survival forest, eXtreme gradient boosting (XGBoost), gradient boosting, and the Cox proportional hazard regression model. The area under the curve (AUC) and C-index were devoted to assessing the performance of the models in predicting HCC prognosis. Results: A total of 1,834 radiomics features were extracted from the computed tomography images of each patient. The clinical risk factors for HCC prognosis were age at diagnosis, TNM stage, and metastasis, which were analyzed using univariate Cox regression. In various models, the efficacy of the combined models generally surpassed that of the radiomics and clinical models. Among four machine learning algorithms, XGBoost exhibited the best performance in combined models, achieving an AUC of 0.979 in the training set and 0.750 in the testing set, demonstrating its strong prognostic prediction capability. Conclusion: The superior performance of the XGBoost-based combined model underscores its potential as a powerful tool for enhancing the precision of prognostic assessments for patients with HCC.

Heart failure with improved ejection fraction: patient characteristics, clinical outcomes and predictors for improvement.

Background: Heart failure with improved ejection fraction (HFimpEF) is a recently recognized entity presenting a diagnostic and therapeutic challenge. Our aim was to characterize the profile of HFimpEF patients and evaluate predictors for EF lack of improvement among heart failure with reduced ejection fraction (HFrEF) patients. Methods: We included ambulatory HFrEF patients (EF≤40%) between January 1, 2015, and September 1, 2022, with two consecutive echocardiography exams at least 6 months apart. HFimpEF was defined as improved EF from ≤40%->40% and by ≥10%. Results: A total of 567 HFrEF patients (72% male, 54.3 ± 14.4 years old) were analyzed. Patients without EF improvement were more likely to be male, had more comorbidities, ischemic cardiomyopathy (ICMP), markers of adverse cardiac remodeling (lower EF and higher left and right ventricular diameters) and presence of late gadolinium enhancement (LGE) in MRI (P < 0.05 for all). In a multivariate analysis, male sex, ICMP, lower EF, larger ventricular size and LGE remained independent predictors for lack of EF improvement. A prediction model for lack of EF improvement including LVEF, LV diameter, diastolic blood pressure and ischemic etiology exhibited an area under the ROC curve of 0.77 (95% CI 0.73-0.81; P < 0.001). HFimpEF patients had better prognosis with lower hospitalizations and mortality rates. Guideline directed medical therapy (GDMT) were associated with improved outcomes in both groups regardless of EF improvement. Conclusions: Lack of improvement in EF among HFrEF patients may be predicted by HF etiology and imaging parameters of adverse cardiac remodeling, and is associated with worse prognosis. GDMT were associated with improved outcomes in both HFimpEF and HFrEF patients.