Independent Prognostic Risk Factor Research Articles

Clinical features and prognostic model for viral encephalitis after allogeneic haematopoietic stem cell transplantation.

The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.

Identification and prognostic analysis of metabolic genes associated with TP53 mutation in multiple myeloma

ABSTRACT Background TP53 gene mutation is crucial in determining the prognosis of Multiple Myeloma (MM) patients. Understanding metabolic genes linked to TP53 mutation is vital for developing targeted therapies for these patients. Method We analyzed The Cancer Genome Atlas (TCGA) dataset to identify genes related to TP53 mutation and metabolism. Using univariate Cox regression and protein–protein interaction (PPI) analysis, we identified key genes. We categorized patients into high and low metabolism groups via non-negative matrix factorization (NMF) clustering, which led to the discovery of relevant differential genes. Integrating these with genes from the Gene Expression Omnibus (GEO) datasets and PPI interactions, we pinpointed crucial metabolic genes associated with TP53 mutation in MM. Additionally, we conducted prognostic analyses involving survival curves and receiver operating characteristic (ROC) charts. Results Our study reveals that the metabolic gene ribonucleotide reductase M2 (RRM2), linked to TP53 mutation, correlates positively with the International Staging System (ISS) stage in MM patients and is an independent prognostic risk factor. In the TCGA dataset, among the 767 patients, the 35 MM patients with TP53 mutation generally had poor survival outcomes. Specifically, the patients with both TP53 mutation and high RRM2 expression had a 2-year survival rate of only 38.87%, whereas those with normal TP53 function and low RRM2 expression had a 2-year survival rate of 86.31% (p < 0.001). Conclusion RRM2 significantly impacts MM prognosis and is associated with TP53 mutation, presenting itself as a potential therapeutic target and prognostic marker for MM.

A study predicting long-term survival capacity in postoperative advanced gastric cancer patients based on MAOA and subcutaneous muscle fat characteristics

BackgroundThe prognosis of advanced gastric cancer (AGC) is relatively poor, and long-term survival depends on timely intervention. Currently, predicting survival rates remains a hot topic. The application of radiomics and immunohistochemistry-related techniques in cancer research is increasingly widespread. However, their integration for predicting long-term survival in AGC patients has not been fully explored.MethodsWe Collected 150 patients diagnosed with AGC at the Affiliated Zhongshan Hospital of Dalian University who underwent radical surgery between 2015 and 2019. Following strict inclusion and exclusion criteria, 90 patients were included in the analysis. We Collected postoperative pathological specimens from enrolled patients, analyzed the expression levels of MAOA using immunohistochemical techniques, and quantified these levels as the MAOAHScore. Obtained plain abdominal CT images from patients, delineated the region of interest at the L3 vertebral body level, and extracted radiomics features. Lasso Cox regression was used to select significant features to establish a radionics risk score, convert it into a categorical variable named risk, and use Cox regression to identify independent predictive factors for constructing a clinical prediction model. ROC, DCA, and calibration curves validated the model’s performance.ResultsThe enrolled patients had an average age of 65.71 years, including 70 males and 20 females. Multivariate Cox regression analysis revealed that risk (P = 0.001, HR = 3.303), MAOAHScore (P = 0.043, HR = 2.055), and TNM stage (P = 0.047, HR = 2.273) emerged as independent prognostic risk factors for 3-year overall survival (OS) and The Similar results were found in the analysis of 3-year disease-specific survival (DSS). The nomogram developed could predict 3-year OS and DSS rates, with areas under the ROC curve (AUCs) of 0.81 and 0.797, respectively. Joint calibration and decision curve analyses (DCA) confirmed the nomogram’s good predictive performance and clinical utility.ConclusionIntegrating immunohistochemistry and muscle fat features provides a more accurate prediction of long-term survival in gastric cancer patients. This study offers new perspectives and methods for a deeper understanding of survival prediction in AGC.

Association of COPD with adverse outcomes in heart failure patients with preserved ejection fraction.

We performed a systematic review and meta-analysis to detect the impact of chronic obstructive pulmonary disease (COPD) on the prognosis of heart failure patients with preserved ejection fraction (HFpEF). We systematically screened eligible literature from three electronic databases, PubMed, EMBASE and Cochrane Library, up to April 2023. Two researchers participated in data collection independently. Risk ratios (RRs) from included studies with 95% confidence intervals (CIs) were pooled in the Review Manager version 5.40 software using a random-effects model for analysis. A total of 11 studies (3 post hoc analyses of RCTs and 8 observational studies) with 18602 participants were included in this meta-analysis. After pooling all the data from eligible studies, our results indicated that COPD was associated with an increased risk of hospitalization (RR=1.66, 95% CI, 1.47-1.87, P<0.00001), mortality (RR=1.62, 95% CI, 1.34-1.95, P<0.00001), and the composition of hospitalization or mortality (RR=1.84, 95% CI, 1.35-2.51, P<0.001) in patients with HFpEF. In a subgroup analysis, the risks of cardiovascular-related mortality (RR=1.59, 95% CI, 1.30-1.93, P<0.00001) and post-discharge mortality risk (RR=2.57, 1.34-4.93, P<0.01) were increased in HFpEF patients comorbid with COPD, and these associations were also detected in HF-caused hospitalization (RR=1.64, 95% CI, 1.44-1.87, P<0.00001). Evidence from existing studies supported that COPD was an independent prognostic risk factor for patients with HFpEF. Developing rapid clinical diagnostic indicators and early use of novel drugs such as SGLT-2 and ARNI may improve the prognosis of this population, deserving further study.

Decoding the Expressions, Immune Relevance, and Prognostic Values of Ferroptosis Gene TMEM189: A Pan-Cancer Analysis.

TMEM189 is a recently discovered transmembrane protein involved in ether glycerophospholipid synthesis and ferroptosis regulation. However, its role in tumors are not well understood. To elucidate the oncogenic effects and prognostic values of TMEM189 in tumors. We performed a pan-cancer analysis of TMEM189 using various databases, bioinformatics and statistical tools, and tissue microarray analysis. TMEM189 is generally upregulated in tumors compared to normal tissues. High TMEM189 expression is linked to reduced promoter methylation. TMEM189 exhibits a negative correlation with immunogenic markers, immune cell infiltration, and expression of immune checkpoint genes (ICGs) in most cancers, implicating its immunosuppressive role in tumor microenvironments (TME). The interacting and similar genes with TMEM189 were involved in hotspot signaling pathways in pan-cancer. TMEM189 overexpression is usually associated with poor prognosis, especially an independent prognostic risk factor for BLCA, BRCA, LUAD, MESO, LIHC and SKCM. TMEM189 is overexpressed and exerts immunosuppressive effects in many tumors with a significant association with poor prognosis, suggesting its potential as a therapeutic target in cancer treatment.

Long-term oncologic outcomes following breast cancer surgery in adolescents and young adults: a single-center retrospective analysis.

Breast cancer (BC) in adolescents and young adults (AYAs, aged 15-39 years), remains inadequately understood. The incidence of BC in AYAs has been steadily increasing, making it the second leading cause of cancer-related mortality among females aged 0-39 globally. This study aimed to elucidate the clinical characteristics and long-term outcomes of AYAs and older adults (OAs, aged > 39 years) with BC who underwent surgery. From January 2011 to June 2017, BC patients who underwent surgery were enrolled in this study and divided into AYA group and OA group. Clinical characteristics, recurrence-free survival (RFS), and overall survival (OS) were compared between these two groups, both before and after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard regression analyses were performed to assess the influence of age on OS and RFS. Compared to the OA group, the AYA group exhibited a younger age at menarche (p < 0.001), a lower prevalence of menopausal status (p < 0.001), a reduced occurrence of comorbid conditions (p < 0.001), fewer instances of undergoing mastectomy (p = 0.031), a higher incidence of Triple-Negative Breast Cancer (TNBC) (p = 0.046), and elevated Ki-67 levels (p = 0.036). In terms of prognostic outcomes, within the study cohort, AYAs had a higher mortality rate and poorer long-term survival compared to OAs, both before and after PSM. In the PSM cohort, AYAs experienced a significantly shorter median OS (p < 0.001) and RFS (p < 0.001). Young age (15-39 years) emerged as an independent risk factor for OS (HR 2.659, 95% CI 1.385-5.106, p = 0.003) and RFS (HR 3.235, 95% CI 2.085-5.022, p < 0.001) in BC patients following surgery. Significant differences were identified in the clinicopathological characteristics between AYA and OA patients with BC. In comparison to OA patients, AYA patients exhibited a less favorable long-term prognosis, with young age emerging as an independent prognostic risk factor for both OS and RFS in BC patients following surgery. Further investigations are warranted to develop age-specific therapeutic approaches for AYA BC patients.

Nomogram for Predicting Survival in Locally Advanced Cervical Cancer with Concurrent Chemoradiotherapy plus or Not Adjuvant Chemotherapy: A Retrospective Analysis Based on 2018 FIGO Staging.

Background: The comprehensive treatment mode of combining concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (AC) is a commonly used mainstream model in the clinical practice of locally advanced cervical cancer (LACC). However, the necessity for AC after CCRT lacks sufficient evidence-based medical support. This study constructs a predictive model for the survival time dependence of CCRT ± AC for LACC based on the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging with internal validation, the prognosis was assessed with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin, and provides guidance for future stratified treatment. Materials and Methods: The retrospective analysis included 482 patients with LACC who CCRT from January 2016 to January 2023. Patients who used the 2009 FIGO staging were all standardized for the 2018 FIGO staging. The 482 patients with LACC were divided into a training set (n = 290) and a validation set (n = 192) at a ratio of 6:4. COX multivariate regression model and LASSO regression were used to screen for independent prognostic factors affecting progression-free survival (PFS) and overall survival (OS), and a nomogram clinical prediction model was constructed based on these factors. Evaluate the effectiveness of the model through the receiver operating characteristic curve, calibration curve, decision curve, risk heat map, and survival curves for risk stratification. Results: The PFS and OS independent prognostic risk factors affecting the 2018 FIGO staging of LACC during CCRT were validated to be similar to the 2009 FIGO staging prediction model reported in previous literature. In the training cohort, area under the curve (AUC) values at 1, 3, and 5 years were 0.941, 0.882, and 0.885 for PFS, and 0.946, 0.946, and 0.969 for OS, respectively. When applied to a test cohort, the model also showed accurate prediction result (AUC at 1, 3, and 5 years were 0.869, 0.891, and 0.899 for PFS, and 0.891, 0.941 and 0.878 for OS, respectively). Subgroup analysis suggests that patients with LACC, adenocarcinoma, stage IVA, pelvic lymph node metastasis, pretreatment hemoglobin ≤100 g/l and residual tumor diameter >2 cm, who received CCRT in the 2018 FIGO stage, may benefit more from adjuvant chemtherapy. Conclusions: Based on the 2018 FIGO staging, a nomogram prediction model for PFS and OS in patients with LACC undergoing CCRT was developed. The model, established by combining weighted clinical and pathological factors, can provide more personalized treatment predictions in clinical practice. For patients with high-risk factors such as residual tumor diameter > 2 cm after CCRT for LACC, AC may bring benefits.

Association of preoperative elevated lipoprotein (a) with poor survival in patients with biliary tract cancers.

Biliary tract cancers have garnered significant attention due to their highly malignant nature. The relationship between abnormal lipid metabolism and tumor occurrence and development is a research hotspot. However, its correlation with biliary tract cancers is unclear. We enrolled 78 patients with biliary tract cancers and obtained data on clinical characteristics, pathological findings, and preoperative blood lipid indices, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and lipoprotein (a) [Lp(a)]. Receiver operating characteristic (ROC) curves were used to determine the optimal predictive cutoff values of lipid indicators among the participants. Independent risk factors were determined using Cox regression, and survival was predicted using the Kaplan-Meier method. Statistical analyses were performed using SPSS software. Univariate Cox regression analysis revealed that the body mass index (BMI), tumor location, surgical margin, N stage, and abnormally increased LDL-C, TG, and Lp(a) levels were significantly associated with poor prognosis of biliary tract cancers (p < 0.05). Multifactor Cox regression demonstrated that only N stage (HR = 3.393, p < 0.001) and abnormally increased Lp(a) levels (HR = 2.814, p = 0.004) were significantly associated with shorter survival. N stage and Lp(a) were identified as independent prognostic risk factors for patients with biliary tract cancers. This study presents Lp(a) as a novel biochemical marker that can guide clinical treatment strategies for patients with biliary tract cancers. More effective treatment options and intensive postoperative testing should be considered to prolong the survival of these patients with preoperative abnormal lipid metabolism.

Identification of PATL1 as a prognostic and immunotherapeutic predictive factor for nasal-type natural killer/T-cell lymphoma and head and neck squamous cell carcinoma

This research examines the function of protein associated with topoisomerase II homolog 1 (PATL1) in nasal-type natural killer/T-cell lymphoma (NKTCL) and head and neck squamous cell carcinoma (HNSCC). We analyzed bulk RNA-seq data from NKTCL, nasal polyps, and normal nasal mucosa, identifying 439 differentially expressed genes. Machine learning algorithms highlighted PATL1 as a hub gene. PATL1 exhibited significant upregulation in NKTCL and HNSCC tumor samples in comparison to normal tissues, showing high diagnostic accuracy (AUC = 1.000) for NKTCL. Further analysis of local hospital data identified PATL1 as an independent prognostic risk factor for NKTCL. Data analysis of TCGA and GEO datasets revealed that high PATL1 expression correlated with poorer prognosis in HNSCC patients (p < 0.05). We also constructed a PATL1-based nomogram, which emerged as an independent prognostic predictor for HNSCC after addressing missing values. Additionally, we found a strong correlation between PATL1 and various immune cell infiltrates (e.g., activated.CD4 T cell), and a significant association with the expression of 37 immune checkpoints genes (e.g., CTLA4, PDCD1) and 20 N6-methyladenosine-related genes (e.g., ZC3H13, METTL3) (all p < 0.05). Both TCIA and TIDE algorithms suggested that PATL1 could potentially predict immunotherapy efficacy (p < 0.05). Cellular experiments demonstrated that transfection with a silencing plasmid of PATL1 significantly inhibited the malignant behaviors of SNK6 and FaDu cell lines(p < 0.05). In conclusion, our findings suggest that PATL1 may serve as a valuable prognostic and predictive biomarker in NKTCL and HNSCC, highlighting its significant role in these cancers.

MRTO4 Enhances Glycolysis to Facilitate HCC Progression by Inhibiting ALDOB.

BACKGROUND MRT4 Homolog, Ribosome Maturation Factor (MRTO4) is often upregulated in cancer cells. However, its impact in hepatocellular carcinoma (HCC) is less well understood. Herein, we explored the prognostic and energy metabolism reprogramming role of MRTO4 in HCC. MATERIAL AND METHODS Clinical data were obtained from The Cancer Genome Atlas (TCGA), and the expression of MRTO4 in clinical samples was analyzed. The association between different variables and overall survival (OS) was studied, as well as their potential as independent prognostic factors, using Cox regression analysis. We constructed a nomogram including clinical pathological variables and MRTO4 expression to provide a predictive model for prognosis. Heatmaps, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the relationship between energy metabolism pathways and MRTO4. We used classic molecular biology research methods, including RT-qPCR, Western blotting, CCK8, TUNEL, Clone formation, Transwell assay, ELISA, and immunohistochemistry, to study the role of MRTO4 in promoting the progression of HCC through glycolysis regulation. RESULTS Our study showed that MRTO4 is an independent prognostic risk factor for HCC and that MRTO4 accelerates glycolysis of HCC cells, promotes proliferation and invasion, and suppresses apoptosis of HCC cells. The underlying mechanism involves MRTO4 promoting glycolysis and accelerating HCC by inhibiting ALDOB. CONCLUSIONS Our study revealed a novel mechanism by which MRTO4 promotes glycolysis and accelerates HCC progression, and suggests that inhibiting MRTO4 could be a potential therapeutic strategy for HCC.

Abstract PO5-02-08: Prognostic value of serum lipid levels in breast cancer patients who received neoadjuvant chemotherapy: A retrospective exploratory analysis of the prospective cohort

Abstract 【Background】 Lipid metabolism is one of the most conspicuous metabolic changes in malignant tumors. Previous studies confirmed that higher levels of “adverse lipids” might lead to poor outcomes and lipid-lowering drugs could act as a protective role in improving the prognosis of breast cancer patients. Nevertheless, few studies have clarified the impact of serum lipid levels and their changes on the tumor prognosis. Particularly for breast cancer patients treated with neoadjuvant chemotherapy, little has been studied whether their lipid levels or changes during neoadjuvant chemotherapy can serve as a valid prognostic factor. 【Methods】This study enrolled patients who received surgical treatment after neoadjuvant chemotherapy in Renji Hospital from March 2016 to December 2020. Patients were included if they were female aged 18 years or older; had pathologically confirmed unilateral invasive breast cancer; had tumor of at least 2cm in size without distant metastasis (T1-4, N0-3, M0); and underwent radical surgery for breast cancer successfully after neoadjuvant chemotherapy. We retrospectively gathered the baseline clinicopathological information and lipid metabolism-related biomarkers from electronic medical records. The study endpoints were disease free survival (DFS), overall survival (OS), relapse free survival (RFS), distance recurrence free survival (DRFS), and local recurrence free survival (LRFS). The prognostic value of each lipid levels and their variation levels were systematically evaluated and the importance of lipid biomarkers were ranked by Random Forest. 【Results】 The baseline clinicopathological information and lipid metabolism biomarkers were available from 200 eligible patients. As of the last follow-up in March 2023, 11 patients died, 24 experienced DFS events and 20 underwent RFS events. It showed no significant correlations of lipid levels before (baseline) and after (preoperative) neoadjuvant chemotherapy with any survival outcome. However, we found that the relative increase of low-density lipoprotein (LDL) led to poorer DFS (P=0.003), RFS (P=0.01), DRFS (P=0.01), and LRFS (P=0.0039), meanwhile the relative increase of total cholesterol (TC) and non-high-density lipoprotein (NHDL) during neoadjuvant period was significantly related to the worse prognosis (TC, DFS P=0.0084; NHDL, DFS P=0.031, RFS P=0.009) as well. After adjusted by multiple factors, the adverse impacts of increasing TC (DFS P=0.005; RFS P=0.026), LDL (DFS P=0.004; RFS P=0.006) and NHDL (DFS P=0.032; RFS P=0.014) on DFS or RFS were still maintained. The results of Random Forest revealed that LDL changes and Body Mass Index (BMI) ranked higher in terms of predicting survival outcomes. Based on these data, BMI &amp;gt;25.4 kg/m2 or LDL elevation &amp;gt;0.54 mmol/L were defined as High-risk Lipid Metabolism (HLM), while BMI ≤ 25.4 kg/m2 and LDL elevation ≤ 0.54 mmol/L were regarded as Low-risk Lipid Metabolism (LLM). Compared to LLM, HLM had a worse OS (P=0.026), DFS (P=0.0011) and RFS (P=0.0011). 【Conclusion】Our study demonstrated that the relative elevation of LDL, TC and NHDL levels during neoadjuvant chemotherapy is an independent prognostic risk factor for breast cancer patients. It was also the first time to propose the concept of high-risk lipid metabolism (HLM). 【keywords】Breast cancer, Lipid metabolism, Low-density lipoprotein (LDL), Body Mass Index (BMI), Prognosis. Citation Format: Xinru Chen, Wenjin Yin, Yingying Zhao, Jinsong Lu. Prognostic value of serum lipid levels in breast cancer patients who received neoadjuvant chemotherapy: A retrospective exploratory analysis of the prospective cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-08.

The effect of CXCL12 on survival outcomes of patients with viral hepatitis-associated hepatocellular carcinoma after hepatectomy

BackgroundThe CXCL12-CXCR4/CXCR7 axis is garnering growing attention. But the comprehension of its function in the progression of HCC remains controversial. The purpose of this study was to investigate the effects of CXCL12 and its receptor on the prognosis of patients with viral hepatitis-associated HCC after hepatectomy. MethodsA total of 86 patients had been enrolled who had undergone hepatectomy for HCC and followed up to July 31, 2019, and their clinicopathological and follow-up data were recorded. Tumor and peritumoral tissues were obtained to detect the expression of CXCL12, CXCR4, and CXCR7 using immunohistochemistry. Real-time polymerase chain reaction was utilized to detect hepatitis B or C virus loads, while survival analysis was performed using the Kaplan–Meier method. Furthermore, the Cox proportional hazards regression model was employed to analyze the factors affecting the prognosis. ResultsThe results revealed that the CXCL12, CXCR4, and CXCR7 expression in tumor tissues was lower than in the corresponding non-tumor tissues in 20.93 %, 22.09 %, and 23.26 % of the patients, respectively, and that only CXCL12 was found to be related to the extrahepatic invasion of HCC. The survival analysis and Cox regression showed that only CXCL12 was associated with the postoperative survival of patients with HCC, and that it was an independent prognostic risk factor in the CXCL12-CXCR4/CXCR7 axis. The CXCL12low group represented shorter progression-free survival and lower overall survival rates. However, the subgroup analysis displayed that the survival difference associated with CXCL12 was only manifested in patients with higher expression of CXCR4 or CXCR7 in HCC, as compared to the surrounding tissues. ConclusionsOur findings suggest that, when assessing the prognostic significance of CXCL12 in HCC, it is essential to consider the expression level of its receptor. Nevertheless, CXCL12 can potentially serve as a promising prognostic marker for HCC.

Construction and validation of "WCH-nomogram" for predicting the prognosis after resection of colorectal liver metastases.

The prognostic predictive tool for patients with colorectal liver metastasis (CRLM) is limited and the criteria for administering preoperative neoadjuvant chemotherapy in CRLM patients remain controversial. This study enrolled 532 CRLM patients at West China Hospital (WCH) from January 2009 to December 2019. Prognostic factors were identified from the training cohort to construct a WCH-nomogram and evaluating accuracy in the validation cohort. Receiver operating characteristic (ROC) curve analysis was used to compare the prediction accuracy with other existing prediction tools. From the analysis of the training cohort, four independent prognostic risk factors, namely tumor marker score, KRAS mutation, primary lymph node metastasis, and tumor burden score were identified on which a WCH-nomogram was constructed. The C-index of the two cohorts were 0.674 (95% CI: 0.634-0.713) and 0.655 (95% CI: 0.586-0.723), respectively, which was better than the previously reported predication scores (CRS, m-CS and GAME score). ROC curves showed AUCs for predicting 1-, 3-, and 5-year overall survival (OS) of 0.758, 0.709, and 0.717 in the training cohort, and 0.860, 0.669, and 0.692 in the validation cohort, respectively. A cutoff value of 114.5 points was obtained for the WCH-nomogram total score based on the maximum Youden index of the ROC curve of 5-year OS. Risk stratification showed significantly better prognosis in the low-risk group, however, the high-risk group was more likely to benefit from neoadjuvant chemotherapy. The WCH-nomogram demonstrates superior prognostic stratification compared to prior scoring systems, effectively identifying CRLM patients who may benefit the most from neoadjuvant chemotherapy.

Prognostic and diagnostic effects of high serum midkine levels in patients with hepatocellular carcinoma.

Midkine (MK) is a soluble cytokine, and its serum levels strongly correspond to protein expression levels in tumors. The present study aimed to clarify the clinicopathological and prognostic significance of serum MK (s-MK) in patients with hepatocellular carcinoma (HCC). Serum samples were obtained before surgery from 123 patients with HCC who had undergone surgery between January 2012 and December 2020. The receiver operating characteristic curve revealed that the best cut-off value for s-MK in differentiating HCC from healthy cases was 426 pg/ml. The clinicopathological variables and overall survival of patients were compared between the s-MK-positive group and s-MK-negative group. The sensitivity, specificity and accuracy of s-MK were 82.1, 97.4 and 88.0%, respectively. An s-MK-positive status was significantly associated with the number of tumors (≥2). The positivity rate of s-MK was significantly higher compared with that of α-fetoprotein and protein-induced by vitamin K absence-II. In total, only 28% of the patients were positive for s-MK. The s-MK-positive group showed significantly worse overall survival compared with the s-MK-negative group. Moreover, multivariate analysis revealed that an s-MK-positive status was independently associated with poor prognosis. s-MK was useful in detecting early HCC. The findings of this study indicated that the s-MK-positive status is associated with the number of tumors and can act as an independent prognostic risk factor.

Pretreatment CD8 + PD-1 + to CD4 + PD-1 + ratio is associated with the prognosis of advanced melanoma patients treated with PD-1 inhibitors.

The aim of this study was to determine whether the pretreatment CD8 + PD-1 + to CD4 + PD-1 + (PERLS) ratio is an independent risk prognostic factor of advanced melanoma patients. We retrospectively analyzed the efficacy and flow cytometry data from advanced melanoma patients who received PD-1 inhibitor as monotherapy between January 1, 2018 and January 26, 2022. Fifty-nine patients were enrolled, the PERLS cutoff was 1.125. PERLS did not correlate with clinical characteristics but were significantly associated with baseline CD8 + , CD4 + , and CD8 + PD-1 + T cells. The mean overall survival and the progression-free survival were 45.8 and 17.1 months for the low PERLS group (n = 39), compared with 29.9 ( P = 0.001) and 9.7 ( P = 0.003) months for the high PERLS group ( n = 20), respectively. Pretreatment PERLS might contribute to selecting patients before receiving anti-PD-1 therapy.

Extramedullary infiltration in pediatric acute myeloid leukemia: Results from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative.

The outcome of extramedullary infiltration (EMI) in pediatric acute myeloid leukemia (AML) is controversial, and little is known about the implications of stem cell transplantation (SCT) and gemtuzumab ozogamicin (GO) treatment on patients with EMI. We retrieved the clinical data of 713 pediatric patients with AML from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, and analyzed the clinical and prognostic characteristics of patients with EMI at diagnosis and relapse. A total of 123 patients were identified to have EMI at diagnosis and 64 presented with EMI at relapse. The presence of EMI was associated with age ≤2years, M5 morphology, abnormal karyotype, and KMT2A rearrangements. Hyperleukocytosis and complex karyotype were more prevalent in patients with EMI at relapse. Additionally, patients with EMI at diagnosis had a reduced incidence of FLT3 ITD-/NPM1+, whereas those with EMI at relapse displayed a lower frequency of FLT3 ITD+. Patients with EMI at diagnosis exhibited a lower complete remission (CR) rate at the end of Induction Course 1 and higher relapse incidence. Importantly, EMI at diagnosis independently predicted both shorter event-free survival (EFS) and overall survival (OS). Regarding relapse patients, the occurrence of EMI at relapse showed no impact on OS. However, relapse patients with myeloid sarcoma (MS)/no central nervous system (CNS) exhibited poorer OS compared to those with CNS/no MS. Furthermore, regarding patients with EMI at diagnosis, SCT failed to improve the survival, whereas GO treatment potentially enhanced OS. EMI at diagnosis is an independent adverse prognostic risk factor for pediatric AML, and GO treatment potentially improves survival for patients with EMI at diagnosis.

Tumor-associated macrophage-induced circMRCKα encodes a peptide to promote glycolysis and progression in hepatocellular carcinoma

The tumor-associated macrophages (TAMs) play multifaceted roles in the progression of hepatocellular carcinoma (HCC). However, the involvement of circular RNAs in the interplay between TAMs and HCC remains unclear. Based on Transwell co-culturing and circular RNA sequencing, this study revealed that TAMs enhanced tumor glycolysis and progression by upregulating circMRCKα in HCC cells. Patients with HCC who exhibited elevated circMRCKα levels presented significantly reduced overall survival and greater cumulative recurrence. Notably, we identified a novel functional peptide of 227 amino acids named circMRCKα-227aa, encoded by circMRCKα. Mechanistically, circMRCKα-227aa bound to USP22 and enhanced its protein level to obstruct HIF-1α degradation via the ubiquitin-proteasome pathway, thereby augmenting HCC glycolysis and progression. In clinical HCC samples, a positive correlation was observed between the expression of circMRCKα and the number of infiltrating CD68+ TAMs and expression of USP22. Furthermore, circMRCKα emerged as an independent prognostic risk factor both individually and in conjunction with CD68+ TAMs and USP22. This study illustrated that circMRCKα-227aa, a novel TAM-induced peptide, promotes tumor glycolysis and progression via USP22 binding and HIF-1α upregulation, suggesting that circMRCKα and TAMs could be combined as therapeutic targets in HCC.

The differential expression of AFF3 in cervical cancer and its correlation with clinicopathological features and prognosis

Background Cervical cancer (CC) is the second most common malignancy in women, and identifying biomarkers of CC is crucial for prognosis prediction. Here, we investigated the expression of AF4/FMR2 Family Member 3 (AFF3) in CC and its association with clinicopathological features and prognosis. Methods Tumour and adjacent tissues, along with clinicopathological features and follow-up information, were collected from 78 patients. AFF3 expression was assessed using quantitative real-time polymerase chain reaction and Western blotting. The correlation between AFF3 expression and CC symptoms was using chi-square test. The 5-year overall survival (OS) was analysed using the Kaplan-Meier method. The Univariate analysis of prognostic risk factors was conducted using the COX proportional hazards model, followed by multivariate COX regression analysis including variables with p < 0.01. Results AFF3 expression was downregulated in CC, and its levels were correlated with lymph node metastasis (LNM) and International Federation of Gynaecology and Obstetrics (FIGO) stage. Patients with low AFF3 expression had a lower 5-year OS rate (52.78%, 19/36). Postoperative survival was reduced in patients with histological grade 3 (G3), myometrial invasion (depth ≥ 1/2), lymphovascular space invasion, LNM, and advanced FIGO stage. Low expression of AFF3 (HR: 2.848, 95% CI: 1.144–7.090) and histological grade G3 (HR: 4.393, 95% CI: 1.663–11.607) were identified as independent prognostic risk factors in CC patients. Conclusion Low expression of AFF3 and histological G3 are independent predictors of poor prognosis in CC patients, suggesting that AFF3 could serve as a potential biomarker for prognostic assessment in CC.

The impact of modified T3 sub-staging on the prognosis of gallbladder cancer patients

Objective: To explore the value of a new modified T3 sub-staging for the prognosis evaluation in gallbladder cancer patients. Methods: This is a retrospective case-series study. The clinical data of patients with pathologically confirmed stage T3 gallbladder cancer who were admitted to the Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2021 were retrospectively analyzed. A total of 190 patients were enrolled in this study, 67 males and 123 females, with an age (M(IQR)) of 63(14) years (range:17 to 88 years). The stage T3 was divided into four sub-stages according to the site of tumor invasion: (1) T3a:tumor perforates the serosa,but not invading the liver and one other adjacent structure; (2) T3b:tumor perforates the serosa and invades one other adjacent structure,but not the liver; (3) T3c:tumor perforates the serosa and invades the liver,but not one other adjacent structure; (4) T3d:tumor perforates the serosa,invades the liver and one other adjacent structure. To evaluate the application value of this modified sub-staging,the Kaplan-Meier method was used to draw the survival curve,univariate analysis and multivariate analysis were done using the Log-rank test and Cox proportional hazard model respectively. Results: According to the modified T3 sub-staging method,34 patients (17.9%) were in stage T3a,24 cases(12.6%) were in stage T3b, 97 cases (51.1%) were in stage T3c, and 35 cases (18.4%) were in stage T3d. The median survival time of patients in stages T3a,T3b,T3c and T3d after radical resection was 72.0 months, 32.0 months, 12.0 months and 10.0 months, respectively. The 1-, 3-, and 5-year survival rates of patients in stage T3a, T3b, T3c and T3d were 79.4%, 53.3%, and 53.3%; 79.2%, 44.6%, and 26.0%;49.5%,27.5%,and 18.1%;42.9%,15.9%, and 15.9% (χ2=18.349,P<0.01),respectively. Univariate analysis showed that gallbladder stones,pathological differentiation,perineural invasion, N stage,postoperative adjuvant therapy and modified T3 substage were factors affecting patient prognosis(all P<0.05). Cox multivariate analysis showed that modified sub-stages with T3c (HR=2.043, 95%CI:1.176 to 3.549) and T3d(HR=2.419, 95%CI:1.284 to 4.555), accompanied by gallbladder stones (HR=1.661,95%CI:1.150 to 2.398),pathological differentiation with poorly differentiated(HR=1.709,95%CI:1.198 to 2.438), and the N stage with N1 and N2(HR=1.602, 95%CI:1.090 to 2.355, 2.714, 95%CI: 1.621 to 4.544) were independent prognostic risk factors for patients in stage T3,while postoperative adjuvant chemotherapy(HR=0.351) was a protective factor for prognosis. There was no statistically significant difference in survival between patients with stage T3a and T3b who underwent hepatic wedge resection and liver segment or major resection (P=0.402). For patients with stage T3c and T3d with liver invasion,the survival difference after hepatic wedge resection and segmental or major resection was statistically significant (P=0.008). Conclusion: The modified T3 sub-staging system based on the depth and direction of tumor invasion maybe helpful to further stratify the prognosis of patients with gallbladder cancer.

Risk factors for unfavorable outcome after spontaneous intracerebral hemorrhage in elderly patients

BackgroundSpontaneous intracerebral hemorrhage (SICH) of the elderly is a devastating form of stroke with a high morbidity and economic burden. There is still a limited understanding of the risk factors for an unfavorable outcome where a surgical therapy may be less meaningful. Thus, the aim of this study is to identify factors associated with unfavorable outcome and time to death in surgically treated elderly patients with SICH. MethodsWe performed a single-center retrospective study of 70 patients (age > 60 years) with SICH operated between 2008 and 2020. Functional outcome was assessed by modified Rankin Scale. Various clinical and neuroradiological variables including type of neurosurgical treatment, anatomical location of hemorrhage, volumetry and distribution of hemorrhage were assessed. Univariate and multivariate logistic regression models were performed. Length of stay (LOS) and hospital costs are presented. ResultsThe overall mortality (mean follow-up time of 22 months) in this study was 32/70 patients (45.71%), 30-days mortality was 8/70 (11.42%), and 12-months mortality was 22/70 (31.43%). Average LOS was 73.5 days with a median of 58, 766 € estimated in hospital costs per patient. Multivariate analysis for 12-months mortality was significant for intraventricular hemorrhage (IVH) (p = 0.007, HR = 1.021, 95% CI = 1.006 – 1.037). ROC analysis for 12-months mortality for IVH volume >= 7 cm3 presented an are under the curve of 0.658. ConclusionsWe identified IVH volume > 7 cm3 as an independent prognostic risk factor for mortality in elderly patients after SICH. This may help clinicians in decision-making for this critical and growing subgroup of patients.