Significant Difference In Prognosis Research Articles

Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes.

Lysosomes possess a multitude of biological functions and are known to play a crucial role in the proliferation and metastasis of head and neck squamous cell carcinoma (HNSCC). This study aims to systematically investigate the potential role of lysosomes-related genes (LRGs) in the development of heterogeneity and prognosis in HNSCC. Publicly available transcriptome and clinical data of HNSCC were obtained and analyzed using consensus clustering to identify molecular subtypes. A risk model based on LRGs was developed and evaluated, including its correlation with clinical features, immune infiltration, drug sensitivity, and response to immune therapy. Gene set enrichment analysis was conducted to explore relevant pathways, and a prognostic nomogram model for HNSCC was constructed and evaluated. In this study, we identified 542 LRGs that exhibited differential expression in HNSCC, with 116 of these being significantly associated with overall survival. Two LRGs-derived molecular subtypes were identified, which displayed significant differences in prognosis and immune cell infiltration. Additionally, a prognostic risk model was developed, which included 13 LRGs. This model successfully divided HNSCC into low-risk and high-risk groups with different prognoses and immune cell infiltrations. The LRGs-derived risk signature was associated with immune infiltration, clinical features, drug sensitivity and immunotherapy response. The good prognosis of the low-risk group was linked to the activation of immune response-related processes and the inhibition of pathways such as necroptosis and neutrophil extracellular trap formation. Patients in the low-risk group had better immune therapy response, while those in the high-risk group had higher drug sensitivity. Finally, our nomogram, which combines clinical N staging and LRG-derived model, demonstrated excellent prognostic evaluation performance as shown by decision curve analysis and calibration curve. The study provides a comprehensive analysis of the expression and prognostic significance of LRGs in HNSCC, leading to the identification of 2 distinct molecular subtypes and the development of a risk model based on LRGs.

Clinical significance of intraperitoneal paclitaxel combined with systemic chemotherapy for gastric cancer with peritoneal metastasis.

Despite investigations of intraperitoneal paclitaxel as a personalized treatment for peritoneal metastasis of gastric cancer, few studies have evaluated its prognostic impact on conversion surgery for unresectable gastric cancer with peritoneal metastasis. Our study aimed to close this gap in knowledge. We retrospectively enrolled 128 patients who underwent chemotherapy for peritoneal metastasis from gastric cancer and assigned them into intraperitoneal (IP) (n = 36) and non-IP (n = 92) groups, based on the use of intraperitoneal paclitaxel plus systemic chemotherapy. Disease control rates were 94% and 69% in the IP and non-IP groups, respectively, with the former having a significantly higher tumor response rate than the latter (p < 0.01). The median survival times in the IP and non-IP groups were 665 and 359days, respectively, with the former having significantly better prognosis than the latter (p = 0.02). Fifteen (42%) and sixteen (17%) patients underwent conversion surgery after chemotherapy in the IP and non-IP groups, respectively, with the former having a significantly higher conversion surgery induction rate than the latter (p < 0.01). Although the prognosis of the conversion surgery group was significantly better than that of the non-conversion surgery group (p < 0.01), there was no significant difference in prognosis between patients in the IP and non-IP groups who underwent conversion surgery (p = 0.22). Multivariate analysis identified performance status and conversion surgery as independent prognostic factors (all p < 0.01). Our study demonstrated that the IP chemotherapy was one of important factors for conversion surgery induction, while it was not a risk factor for prognosis.

Prognosis and local treatment strategies of breast cancer patients with different numbers of micrometastatic lymph nodes

BackgroundLymph node micrometastasis is an important prognostic factor in breast cancer, but patients with different numbers of involved lymph nodes are all divided into the same N1mi stage without distinction. We designed this study to compare the prognosis and local treatment recommendations of N1mi breast cancer patients with different numbers of micrometastatic lymph nodes.Patients and methodsA total of 27,032 breast cancer patients with T1-2N1miM0 stage from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2019) who underwent breast surgery were included in this retrospective study. Patients were divided into three groups for prognosis comparison according to the number of micrometastatic lymph nodes: N1mi with 1 (Nmi = 1), 2 (Nmi = 2), or more (Nmi ≥ 3) involved lymph nodes. We explored the characteristics and survival outcomes of the population receiving different local treatments, including different axillary surgery types and whether receiving radiotherapy or not. Univariate and multivariate Cox proportional hazards regression analysis were used to compare the overall survival (OS) and breast cancer-specific survival (BCSS) in different groups. Stratified analyses and interaction analyses were also applied to explore the predictive significance of different involved lymph nodes numbers. Propensity score matching (PSM) method was utilized to balance the differences between groups.ResultsUnivariate and multivariate Cox regression analysis indicated that nodal status was an independent prognostic factor. After adjustment for other prognostic factors, there was a significant difference in prognosis between Nmi = 1 group and Nmi = 2 group [adjusted hazard ratio (HR) 1.145, 95% confidence interval (CI): 1.047–1.251, P = 0.003], and patients with Nmi ≥ 3 group had a significantly poorer prognosis (adjusted HR 1.679, 95% CI 1.589–2.407; P < 0.001). The proportion of N1mi patients only underwent sentinel lymph nodes biopsy (SLNB) gradually increased from 2010 (Ptrend < 0.001). After adjusting for other factors, N1mi patients who underwent axillary lymph nodes dissection (ALND) was associated with significant survival benefit than SLNB (adjusted HR 0.932, 95%CI 0.874–0.994; P = 0.033), the same goes for receiving radiotherapy (adjusted HR 1.107, 95%CI 1.030–1.190; P = 0.006). Further stratified analysis showed that in the SLNB subgroup, radiotherapy was associated with a significant survival benefit (HR 1.695, 95%CI 1.534–1.874; P < 0.001), whereas in the ALND subgroup, there was no significant prognostic difference with or without radiotherapy (HR 1.029, 95%CI 0.933–1.136; P = 0.564).ConclusionOur study indicates that the increasing number of lymph node micrometastases was associated a worse prognosis of N1mi breast cancer patients. In addition, ALND does provide a significant survival benefit for these patients, while the benefit from local radiotherapy may be of even greater importance.

High SLC20A1 Expression Indicates Poor Prognosis in Prostate Cancer.

High expression of solute carrier family 20 member 1 (SLC20A1) indicates poor clinical outcomes for patients with breast cancer subtypes treated with endocrine therapy and radiotherapy. However, the association between SLC20A1 expression and clinical outcomes in prostate cancer remains to be determined. Open-source datasets (The Cancer Genome Atlas prostate, Stand Up to Cancer-Prostate Cancer Foundation Dream Team, and The Cancer Genome Atlas PanCancer Atlas) were downloaded and analyzed. SLC20A1 expression was analyzed in prostate cancer and normal prostate tissue. Survival analysis using Kaplan-Meier curves and Cox regression analysis were performed to examine patient prognosis, as well as the effects of endocrine therapy and radiotherapy on high SLC20A1 expression in patients with prostate cancer. SLC20A1 was higher in prostate cancer than in normal prostate tissues. High SLC20A1 expression predicted poor disease-free and progression-free survival. Following endocrine therapy, no significant difference in prognosis was observed between patients with high SLC20A1 and those with low SLC20A1 expression. However, following radiotherapy, high SLC20A1 expression tended to be associated with a poor clinical outcome. SLC20A1 may serve as a prognostic biomarker for prostate cancer, and the recommended treatment for patients with high SLC20A1 expression is endocrine therapy.

In-hospital recurrence and functional outcome between ischemic stroke caused by intracranial arterial dissection and intracranial atherosclerosis: Retrospective cohort study of the nationwide multicenter registry

Intracranial arterial dissection (ICAD) and intracranial atherosclerotic stenosis (ICAS) are often difficult to differentiate, and studies on their background factors and prognosis are scarce. Information on prognosis, including recurrence, is necessary for stroke care, and clarification of epidemiological and clinical differences between the two diseases is important for appropriately handling their heterogeneity. This study aimed to determine the association of ICAD and ICAS with in-hospital recurrence and prognosis and compare their background and clinical findings. In this multicenter cohort study, we retrospectively analyzed data from the Saiseikai Stroke Database. Adults with ischemic stroke caused by ICAD or ICAS were included in this study. Patients' backgrounds and clinical findings were compared between the ICAD and ICAS groups. The outcome showed an association of ICAD with in-hospital recurrence of ischemic stroke and poor functional outcome relative to ICAS. Multivariable logistic regression analyses were performed to calculate the adjusted odds ratios (ORs) for ICAD with 95% confidence intervals (CIs) for each outcome. Among 15,622 patients registered in the Saiseikai Stroke Database, 2,020 were enrolled (ICAD group: 89; ICAS group: 1,931). In the ICAD group, 65.2% of the patients were aged <64 years. Vascular lesion location was more common in ICAD with the vertebral artery [42 (47.2%)], anterior cerebral artery [20 (22.5%)], and middle cerebral artery (MCA) [16 (18.0%)], and in ICAS with MCA 1046 (52.3%). Multivariable logistic regression analyses of the association between ICAD and in-hospital recurrence and poor functional outcome yielded a crude OR (95% CI) of 3.26 (1.06-9.97) and 0.97 (0.54-1.74), respectively, relative to ICAS. ICAD was associated with a higher in-hospital recurrence than ICAS; however, there was no significant difference in prognosis between the two groups. Differences in background characteristics and vessel lesions may be of interest in these two diseases.

Identification of Exosome-Related Genes Associated with Prognosis and Immune Infiltration Features in Head-Neck Squamous Cell Carcinoma.

The highly immunosuppressive nature of head-neck squamous cell cancer (HNSCC) is not fully understood. Exosomes play crucial roles in the communication between cancer and non-cancer cells, but the clinical significance of the expression of exosome-related genes (ERGs) remains unclear in HNSCC. This study aimed to establish an HNSCC-ERGs model by using mass spectrometry (MS)-based label-free quantitative proteomics in combination with the TCGA primary HNSCC dataset. The study managed to classify the HNSCC patients into two subtypes based on the expression level of prognostic ERGs, which showed significant differences in prognosis and immune infiltration. LASSO regression algorithm was used to establish a risk prediction model based on seven risky genes (PYGL, ACTN2, TSPAN15, EXT2, PLAU, ITGA5), and the high-risk group was associated with poor survival prognosis and suppressive immune status. HPRT1 and PYGL were found to be independent prognostic factors through univariate and multivariate Cox regression analyses. Immune and ssGSEA analysis revealed that HPRT1 and PYGL were significantly related to immunosuppression, immune response, and critical signaling transduction pathways in HNSCC. Immunohistochemistry results further validated the expression level, clinical value, and immunosuppressive function of HPRT1 and PYGL in HNSCC patients. In conclusion, this study established molecular subtypes and a prediction risk model based on the ERGs. Furthermore, the findings suggested that HPRT1 and PYGL might play critical roles in reshaping the tumor microenvironment.

Significance of ypTNM stage in determining the prognosis and therapy after surgery for locally advanced rectal cancer

BackgroundIn the current NCCN guidelines, the prognosis and adjuvant chemotherapy of patients who underwent neoadjuvant chemoradiotherapy (nCRT) are based on pre-radiotherapy clinical TNM (cTNM) stage. However, the value of neoadjuvant pathologic TNM (ypTNM) stage is not clearly described.MethodsThis retrospective study investigated the prognosis and adjuvant chemotherapy which based on ypTNM stage compared to cTNM stage. Between 2010 and 2015, a total of 316 rectal cancer patients who underwent nCRT, followed by total mesorectal excision (TME), were included for analysis.ResultsOur findings revealed that cTNM stage was the only significant independent factor in the pCR group (HR = 6.917, 95% CI: 1.133–42.216, P = 0.038). In the non-pCR group, ypTNM stage was more important than cTNM stage in prognosis (HR = 2.704, 95% CI: 1.811–4.038, P < 0.001). In ypTNM III stage group, there was a statistically significant difference in prognosis between the patients with and without adjuvant chemotherapy (HR = 1.943, 95% CI: 1.015–3.722, P = 0.040), but there was no significant difference in cTNM III stage group (HR = 1.430, 95% CI: 0.728–2.806, P = 0.294).ConclusionsWe concluded that ypTNM stage, rather than cTNM stage, might be a more important factor in the prognosis and adjuvant chemotherapy of patients with rectal cancer who underwent nCRT.

A Study on the Efficacy of Thrombectomy in Patients with Atherosclerotic and Cardioembolic Basilar Artery Occlusion.

Background Studies on basilar artery occlusion are relatively few compared with those of anterior circulation stroke. The aim of the present study was to compare the efficacy of endovascular therapy (EVT) in patients with basilar artery occlusion classified as large artery atherosclerosis (LAA) and cardioembolism (CE), and to analyze the independent risk factors affecting the prognosis of EVT. Methods A total of 123 people were assigned to the LAA and CE groups (97 to the LAA and 26 to the CE). The primary outcome was a modified Rankin Scale (mRS) score of 2 or lower at 90 days. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial hemorrhage and reinfarction. Multiple logistic regression was used to screen out independent risk factors for EVT prognosis of the LAA and CE groups. Results In the analysis, the patients with LAA stroke had better collateral circulation (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [SIR] score of 2-4; 61.9 vs. 19.2%, p = 0.000), and higher angioplasty rate (32.0 vs. 3.8%, p = 0.002). The proportions of patients with a 90-day mRS score of 0 to 2 and 90-day mortality were not found to be statistically significant between the two groups. Multivariate logistic regression analysis indicated that age, SIR, white blood cell, blood glucose, and modified thrombolysis in cerebral infarction were independent risk factors for the poor prognosis of EVT in the LAA group. Conclusion Although there were differences in clinical characteristics and imaging features between LAA and CE, there was no evidence of a significant difference in prognosis after EVT. In addition, the National Institutes of Health Stroke Scale score was not among the independent risk factors affecting the prognosis of the LAA group.

An N6-methyladenosine regulation- and mRNAsi-related prognostic index reveals the distinct immune microenvironment and immunotherapy responses in lower-grade glioma

BackgroundN6-methyladenosine (m6A) modification is involved in tumorigenesis and progression as well as closely correlated with stem cell differentiation and pluripotency. Moreover, tumor progression includes the acquisition of stemness characteristics and accumulating loss of differentiation phenotype. Therefore, we integrated m6A modification and stemness indicator mRNAsi to classify patients and predict prognosis for LGG.MethodsWe performed consensus clustering, weighted gene co-expression network analysis, and least absolute shrinkage and selection operator Cox regression analysis to identify an m6A regulation- and mRNAsi-related prognostic index (MRMRPI). Based on this prognostic index, we also explored the differences in immune microenvironments between high- and low-risk populations. Next, immunotherapy responses were also predicted. Moreover, single-cell RNA sequencing data was further used to verify the expression of these genes in MRMRPI. At last, the tumor-promoting and tumor-associated macrophage polarization roles of TIMP1 in LGG were validated by in vitro experiments.ResultsTen genes (DGCR10, CYP2E1, CSMD3, HOXB3, CABP4, AVIL, PTCRA, TIMP1, CLEC18A, and SAMD9) were identified to construct the MRMRPI, which was able to successfully classify patients into high- and low-risk group. Significant differences in prognosis, immune microenvironment, and immunotherapy responses were found between distinct groups. A nomogram integrating the MRMRPI and other prognostic factors were also developed to accurately predict prognosis. Moreover, in vitro experiments illustrated that inhibition of TIMP1 could inhibit the proliferation, migration, and invasion of LGG cells and also inhibit the polarization of tumor-associated macrophages.ConclusionThese findings provide novel insights into understanding the interactions of m6A methylation regulation and tumor stemness on LGG development and contribute to guiding more precise immunotherapy strategies.

Diagnostic model of low-grade serous ovarian cancer and borderline serous ovarian tumor: Model development and validation based on radiomics.

e17534 Background: Evidence to date indicates that there is a close relationship between low-grade serous ovarian cancer (LGSOC) and serous borderline ovarian tumor, but there is a significant difference in prognosis. Preoperative imaging and clinical information to assess the nature of lesions as accurately as possible is beneficial to the surgical management of patients. Methods: A total of 104 patients who underwent CT examination and surgical treatment for pelvic masses in Qilu Hospital of Shandong University from 2013 to 2021 were included in the study, including 25 patients with low-grade serous ovarian cancer, 34 patients with serous borderline ovarian tumor, and 45 patients with serous cystadenoma. Quantitative image features were extracted from CT and combined with clinical information to construct a diagnostic model. The diagnostic performance was evaluated by ROC and AUC. Results: The diagnostic model was constructed by RFECV (recursive feature elimination and cross validation) together with SVM (support vector machine), random forest and XGBoost (eXtreme Gradient Boosting) algorithms, among which the RFECV combined random forest algorithm model showed the optimal accuracy (0.78) and AUC (0.92). Combined with clinical features, a new diagnostic model was constructed again by RFECV and random forest, and the accuracy (0.91) and AUC (0.96) were further improved. Conclusions: Through the combination of CT image-based radiomics and clinical features, the clinical diagnosis model was successfully constructed, which can accurately evaluate and predict the pathological types of patients, and is expected to be used in clinical practice and guide surgical decision-making.

CORRELATION BETWEEN SOMATIC MUTATIONS AND PROGNOSIS IN PEDIATRIC MATURE B‐CELL LYMPHOMA

Introduction: To investigate the prognostic factors of childhood mature B-cell lymphoma (MBL), especially the significance of somatic mutations in the clinical features and prognosis, by analyzing the clinical chartacteristics, genetic mutation results and prognosis of 133 children with MBL. Methods: Children and adolescents (≤18 years old) with MBL who were admitted from November 2017 to February 2023 were enrolled, and patients with somatic mutations were detected using next-generation sequencing (NGS). The diagnosis includes the completion of pathological examination and center consultation, and the staging is based on the international children's St. Jude staging system, primary patients were treated with the modified LMB89/96 protocol. Refractory or recurrent (r/r) patients were treated with second-line chemotherapy based on ICE and/or CAR-T-cell sequential therapy with different B-cell targets. The factors related to curative effect and prognosis, especially the correlation between the gene mutation spectrum and prognosis, were analyzed. Results: The mutant gene spectrum of 133 patients is shown in Fig.a. According to the time of specimen collection, there were 77 cases of initial diagnosis (initial treatment group) and 56 cases of r/r patients (r/r group). The clinical feature and survival of the 133 patients are summarized in Figure b, c, d, e (P < 0.001) and g. The results showed that patients with a large tumor focus, serous cavity effusion and delayed chemotherapy during treatment had significant difference in prognosis and significantly shortened survival. The top three genes in the initial treatment group were ID3 (53%), TP53 (47%), and CCND3 (30%) (Figure h). The top three genes in the r/r group were TP53 (82%), ID3 (58%), and ARID1A (40%) (Figure j). TP53 was significantly different between the initial treatment group and r/r patients (P < 0.001). Of the 133 patients grouped by efficacy, 70 progressed/relapsed, and 59/70 received CAR T therapy, with an overall response rate (ORR) of 83%. Survival analysis is shown in the figure f. A total of 11/70 patients received second-line chemotherapy, and only 1 patient survived to receive treatment. Compared with second-line chemotherapy, CAR T-cell treatment significantly improved the survival rate (P = 0.008). ARID1Awas significant in patients with poor prognosis after CAR T therapy (P = 0.00081) (Figure k). Keywords: Chemotherapy, Diagnostic and Prognostic Biomarkers, Non-Hodgkin (Pediatric, Adolescent, and Young Adult) No conflicts of interests pertinent to the abstract.

Survival Analysis of Lung Adenocarcinoma Patients with Exon 19 Del and 21 L858R Mutations Receiving EGFR-TKI Treatment

Introduction: Patients with adenocarcinoma of the lung that have a common EGFR mutation, the Exon 19 Del mutation, survive better than those with the Exon 21 L858R mutation. This study examined whether there is a significant difference in prognosis between two common EGFR mutations, namely exon 19 Del and 21 L858R. This study compared OS (overall survival) and PFS (progression-free survival) in NSCLC patients with Exon 19 Del and Exon 21 L858R mutations who received EGFR-TKI targeted therapy at H. Adam Malik Hospital Medan. Methods: This analysis study used a retrospective cohort design to evaluate the OS and PFS of NSCLC patients who underwent EGFR-TKI precision medicine at H. Adam Hospital Malik Medan between January 1, 2017, and December 31, 2020 and also had Exon 19 Del and Exon 21 L858R alterations. Results: A total of 88 people were sampled. The majority of research subjects were male (60.2%). Median OS was eleven months (95 percent CI:9.594-12,406). According to the study's data, eight people (9.1%) survived until the study's ending. The median OS of Exon 19 Del Common Mutation was 11 months (95%CI 9,064-12,936). While Exon 21 L858R group had ten months (95%CI 4,546-15,454). The log-rank test identified no statistical difference in median OS between mutation types (p=0.562). Conclusion: The findings of this study revealed that subjects with Exon 19 Del mutations had a longer median OS and PFS than those with Exon 21 L858R variants. Nevertheless, there was no significant difference in median OS and PFS between study subjects with mutation of Exon 19 Del and Exon 21 L858R, which received the targeted medication.

Morphology of myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPN) are a group of clonal haematological malignancies first described by Dameshek in 1957. The Philadelphia-negative MPN that will be described are polycythaemia vera (PV), essential thrombocythaemia (ET), pre-fibrotic myelofibrosis and primary myelofibrosis (PMF). The blood and bone marrow morphology are essential in diagnosis, for WHO classification, establishing a baseline, monitoring response to treatment and identifying changes that may indicate disease progression. The blood film changes may be in any of the cellular elements. The key bone marrow features are architecture and cellularity, relative complement of individual cell types, reticulin content and bony structure. Megakaryocytes are the most abnormal cell and key to classification, as their number, location, size and cytology are all disease-defining. Reticulin content and grade are integral to assignment of the diagnosis of myelofibrosis. Even with careful assessment of all these features, not all cases fit neatly into the diagnostic entities; there is frequent overlap reflecting the biological disease continuum rather than distinct entities. Notwithstanding this, an accurate morphologic diagnosis in MPN is crucial due to the significant differences in prognosis between different subtypes and the availability of different therapies in the era of novel agents. The distinction between "reactive" and MPN is also not always straightforward and caution needs to be exercised given the prevalence of "triple negative" MPN. Here we describe the morphology of MPN including comments on changes with disease evolution and with treatment.

The identification of metabolism-related subtypes and potential treatments for idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is caused by aberrant repair because of alveolar epithelial injury and can only be effectively treated with several compounds. Several metabolism-related biomolecular processes were found to be involved in IPF. We aimed to identify IPF subtypes based on metabolism-related pathways and explore potential drugs for each subtype. Methods: Gene profiles and clinical information were obtained from the Gene Expression Omnibus (GEO) database (GSE70867 and GSE93606). The enrichment scores for 41 metabolism-related pathways, immune cells, and immune pathways were calculated using the Gene Set Variation Analysis (GSVA) package. The ConsensusClusterPlus package was used to cluster samples. Novel modules and hub genes were identified using weighted correlation network analysis (WGCNA). Receiver operating characteristic (ROC) and calibration curves were plotted, and decision curve analysis (DCA) were performed to evaluate the model in the training and validation cohorts. A connectivity map was used as a drug probe. Results: Two subtypes with significant differences in prognosis were identified based on the metabolism-related pathways. Subtype C1 had a poor prognosis, low metabolic levels, and a unique immune signature. CDS2, LCLAT1, GPD1L, AGPAT1, ALDH3A1, LAP3, ADH5, AHCYL2, and MDH1 were used to distinguish between the two subtypes. Finally, subtype-specific drugs, which can potentially treat IPF, were identified. Conclusion: The aberrant activation of metabolism-related pathways contributes to differential prognoses in patients with IPF. Collectively, our findings provide novel mechanistic insights into subtyping IPF based on the metabolism-related pathway and potential treatments, which would help clinicians provide subtype-specific individualized therapeutic management to patients.

Identification and validation of m5c-related lncRNA risk model for ovarian cancer

Ovarian cancer (OC) is one of the common malignant tumors that seriously threaten women's health, and there is a lack of clinical prognostic predictors, while m5c and lncRNA have been shown to be predictive of multiple cancers, including OC. Therefore, our goal was to construct a risk model for OC based on m5c-related lncRNA.340 m5c-related lncRNA were identified and a novel risk model of OC ground on nine m5C-related lncRNA was constructed using LASSO-COX regression analysis. Kaplan–Meier analysis showed there was a significant difference in prognosis between risk groups. We established a nomogram which was a good predictor of overall survival. In addition, GSEA was enriched in multiple pathways and immune function analysis suggested that immune infiltration varies depending on the risk group. In vitro experiments show that AC005562.1, a key lncRNA of the risk model, is highly expressed in OC cells and promotes OC cell proliferation. Finally, we further explored the potential biological markers of m5c-related lncRNA in OC with WGCNA analysis and established a ceRNA network. In conclusion,we have developed a reliable m5c-related prediction model and performed systematic validation and exploration of various aspects. These results can be used for the assessment of OC prognosis and the discovery of novel biomarkers.

Bioinformatics identification and validation of aging‑related molecular subtype and prognostic signature in breast cancer.

Patients with metastatic breast cancer have a poor clinical outcome, accounting for more than 90 percent of breast cancer-related deaths. Aging could regulate many biological processes in malignancies by regulating cell senescence. The role of aging has not been fully clarified. Consensus cluster analysis was performed to differentiate The Cancer Genome Atlas (TCGA) breast cancer cases. Least absolute shrinkage and selection operator (LASSO) cox regression analysis was performed to construct an aging-related prognostic signature. A total of 118 differentially expressed aging-related genes (ARGs) was obtained in breast cancer. Consensus clustering analysis identified 3 categories of TCGA-breast cancer with significant difference in prognosis and immune infiltration. We also constructed an aging-related prognostic signature for breast cancer, which had a good performance in predicting the 1-year, 3-year and 5-year OS and disease specific survival (DSS) of breast cancer patients. Further single gene analysis revealed that the expression of PIK3R1 was significantly different in different pT and pN stages of breast cancer. Moreover, low expression of PIK3R1 showed resistance to many drugs based on the data of Genomics of Drug Sensitivity in Cancer (GDSC) and Genomics of Therapeutics Response Portal (CTRP). PIK3R1 played a vital role in many well-known cancer-related pathways. The current study identified 3 clusters of TCGA-breast cancer cases with significant differences in prognosis and immune infiltration. We also constructed an aging-related prognostic signature for breast cancer. However, further in vivo and in vitro studies should be conducted to verify these results.

A novel circadian cycle-related gene signature for prognosis prediction of patients with breast cancer.

The extensive and intricate relationships between circadian rhythm and cancer have been reported in numerous studies. However, in breast cancer (BC), the potential role of circadian clock-related genes (CCRGs) in prognosis prediction has not been fully clarified. The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. A CCRGs-based risk signature was established by differential expression analysis, univariate, Lasso and multivariate Cox regression analyses. we conducted a gene set enrichment analysis (GSEA) between groups. A nomogram integrating independent clinical factors and risk score was generated and evaluated by calibration curves and decision curve analysis (DCA). Differentially expression analysis revealed 80 differentially expressed CCRGs, and 27 of them were significantly associated with the overall survival (OS) of BC. BC can be classified into 4 molecular subtypes with significant differences in prognosis based on the 27 CCRGs. Three prognostic CCRGs, including desmocollin 1 (DSC1), LEF1, and protocadherin 9 (PCDH9), were identified to be independent risk factors of BC prognosis and were used to construct a risk score model. BC patients were divided into high- and low-risk groups, and there were significant differences in prognosis between the 2 groups both in the training and validation cohorts. It was found that patients in different groups of race, status, or T stage had significant levels of risk score. Furthermore, patients of different risk levels exhibit varying degrees of sensitivity to vinorelbine, lapatinib, metformin, and vinblastine. GSEA showed that in the high-risk group, immune response-related activities were dramatically repressed whereas cilium-related processes were significantly stimulated. Cox regression analysis demonstrated that age, N stage, radiotherapy and the risk score were independent prognostic risk factors of BC, and a nomogram was established based on these variables. The nomogram exerted a favorable concordance index (0.798) as well as calibration performance, which strongly supports the clinical application of the nomogram. Our study indicated the disruption of the expression of CCRGs in BC and built a favorable prognostic risk model based on 3 independent prognostic CCRGs. These genes may be applied as candidate molecular targets for the diagnosis and therapy of BC.

Investigating the impact of tumor location and size on the risk of recurrence for papillary thyroid carcinoma in the isthmus.

The purpose of the study was to investigate the ability of new parameters in distinguishing high-risk patients of recurrence from isthmic papillary thyroid carcinomas (iPTCs). One hundred sixteen iPTC patients who underwent total thyroidectomy were identified from 3461 PTC patients from 2014 to 2019. Tumor margin to trachea midline distance (TTD), maximum tumor size (TS), and transverse diameter of trachea (TD) were measured on CT images. Cox proportional hazard models served to identify risk factors associated with recurrence-free survival (RFS). The iPTC prognostic formula (IPF = TD/(TTD - TS) - TD/TTD) was evaluated to assess the prognosis. RFS was conducted between the different groups using the Kaplan-Meier analysis. The receiver operating characteristic (ROC) curve of each parameter was drawn to predict recurrence. Central lymph node metastasis (CLNM) and extrathyroidal invasion in iPTC were 58.6% and 31.0%, respectively. Regional recurrence occurred in 16 (13.8%) patients, and no patient died or had distant metastasis. The 3- and 5-year RFS of iPTC were 87.5% and 84.5%, respectively. Gender (p = 0.001) and PLNM (prelaryngeal lymph node metastasis) (p = 0.010) in cPTC (center of iPTC located between two imaginary lines perpendicular to the surface of the skin from the most lateral points of the trachea) and non-cPTC (iPTC patients enrolled in this study excluding cPTC) groups differed significantly. A cut-off point of tumor size >1.1 cm and IPF ≤5.57 were established to have significant differences in prognosis (p = 0.032 and p = 0.005, respectively). Multivariate analysis showed that IPF ≤5.57 was independent prognostic factor for RFS (HR: 4.415, 95%CI: 1.118-17.431, p = 0.034). This study indicated the association between IPF and RFS in iPTC patients and established new models to assess risk factors for recurrence pre-operation. IPF ≤5.57 was significantly associated with poor RFS and might be promising parameters for predicting prognosis and surgical decision-making pre-operation.

Bioinformatics Identification and Validation of Aging‑Related Molecular Subtype and Prognostic Signature in Sarcoma

Aging could regulate many biological processes in malignancies by regulating cell senescence. Consensus cluster analysis was conducted to differentiate TCGA sarcoma cases. LASSO cox regression analysis was performed to construct an aging-related prognostic signature. We identified two categories of TCGA-sarcoma with significant difference in prognosis, immune infiltration and chemotherapy and targeted therapy. Moreover, an aging-related prognostic signature was constructed for sarcoma, which had a good performance in predicting the 3-year and 5-year overall survival of sarcoma patients. We also identified a lncRNA MALAT1/miR-508-3p/CCNA2 regulatory axis for sarcoma. This stratification could provide more evidence for estimating prognosis and immunotherapy of sarcoma.

Identification of novel molecular subtypes and a signature to predict prognosis and therapeutic response based on cuproptosis-related genes in prostate cancer.

Prostate cancer (PCa) is the most common malignant tumor of the male urinary system. Cuproptosis, as a novel regulated cell death, remains unclear in PCa. This study aimed to investigate the role of cuproptosis-related genes (CRGs) in molecular stratification, prognostic prediction, and clinical decision-making in PCa. Cuproptosis-related molecular subtypes were identified by consensus clustering analysis. A prognostic signature was constructed with LASSO cox regression analyses with 10-fold cross-validation. It was further validated in the internal validation cohort and eight external validation cohorts. The tumor microenvironment between the two risk groups was compared using the ssGSEA and ESTIMATE algorithms. Finally, qRT-PCR was used to explore the expression and regulation of these model genes at the cellular level. Furthermore, 4D Label-Free LC-MS/MS and RNAseq were used to investigate the changes in CRGs at protein and RNA levels after the knockdown of the key model gene B4GALNT4. Two cuproptosis-related molecular subtypes with significant differences in prognoses, clinical features, and the immune microenvironment were identified. Immunosuppressive microenvironments were associated with poor prognosis. A prognostic signature comprised of five genes (B4GALNT4, FAM83D, COL1A, CHRM3, and MYBPC1) was constructed. The performance and generalizability of the signature were validated in eight completely independent datasets from multiple centers. Patients in the high-risk group had a poorer prognosis, more immune cell infiltration, more active immune-related functions, higher expression of human leukocyte antigen and immune checkpoint molecules, and higher immune scores. In addition, anti-PDL-1 immunotherapy prediction, somatic mutation, chemotherapy response prediction, and potential drug prediction were also analyzed based on the risk signature. The validation of five model genes' expression and regulation in qPCR was consistent with the results of bioinformatics analysis. Transcriptomics and proteomics analyses revealed that the key model gene B4GALNT4 might regulate CRGs through protein modification after transcription. The cuproptosis-related molecular subtypes and the prognostic signature identified in this study could be used to predict the prognosis and contribute to the clinical decision-making of PCa. Furthermore, we identified a potential cuproptosis-related oncogene B4GALNT4 in PCa, which could be used as a target to treat PCa in combination with cuproptosis.