Evaluation Of Prognosis Research Articles

Neutrophil extracellular trap-associated protein in cerebrospinal fluid for prognosis evaluation of adult bacterial meningitis: a retrospective case-control study.

Central nervous system infections, typified by bacterial meningitis, stand as pivotal emergencies recurrently confronted by neurologists. Timely and precise diagnosis constitutes the cornerstone for efficacious intervention. The present study endeavors to scrutinize the influence of inflammatory protein levels associated with neutrophils in cerebrospinal fluid on the prognosis of central nervous system infectious maladies. This retrospective case series study was undertaken at the Neurology Department of the Second Hospital of Shandong University, encompassing patients diagnosed with infectious encephalitis as confirmed by PCR testing and other diagnostic modalities spanning from January 2018 to January 2024. The quantification of MPO and pertinent inflammatory proteins within patients' cerebrospinal fluid was accomplished through the utilization of ELISA. We enlisted 25 patients diagnosed with bacterial meningitis, ascertained through PCR testing, and stratified them into two groups: those with favorable prognoses (n = 25) and those with unfavorable prognoses (n = 25). Following assessments for normality and variance, notable disparities in CSF-MPO concentrations emerged between the prognostic categories of bacterial meningitis patients (P < 0.0001). Additionally, scrutiny of demographic data in both favorable and unfavorable prognosis groups unveiled distinctions in CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, CSF-TNF-α levels, with correlation analyses revealing robust associations with MPO. ROC curve analyses delineated that when CSF-MPO ≥ 16.57 ng/mL, there exists an 83% likelihood of an adverse prognosis for bacterial meningitis. Similarly, when CSF-IL-1β, CSF-IL-6, CSF-IL-8, CSF-IL-18, and CSF-TNF-α levels attain 3.83pg/mL, 123.92pg/mL, 4230.62pg/mL, 35.55pg/mL, and 35.19pg/mL, respectively, there exists an 83% probability of an unfavorable prognosis for bacterial meningitis. The detection of neutrophil extracellular traps MPO and associated inflammatory protein levels in cerebrospinal fluid samples holds promise in prognosticating bacterial meningitis, thereby assuming paramount significance in the prognostic evaluation of patients afflicted with this condition.

Upregulated lncRNA LINC01128 in colorectal cancer accelerates cell growth and predicts malignant prognosis through sponging miR-363-3p

PurposeColorectal cancer (CRC) refers to high-mortality tumors arising in the colon or rectum with a high rate of recurrence. The involvement of long non-coding RNAs (lncRNAs) contributes to the treatment and prognosis evaluation of CRC, and brings a new direction for the radical cure of patients. To identify the pathological mechanism and regulation of lncRNA LINC01128 (LINC01128) on CRC cells, and analyze its potential prognostic value.MethodsLINC01128 level in tissue and cell specimens from 122 CRC patients was evaluated by RT-qPCR. The clinical significance and prognostic value of LINC01128 in CRC were analyzed via Kaplan–Meier and Cox analysis. CCK8 and Transwell assays were used to study the function of LINC01128 in vitro. The relationship between LINC01128 and miR-363-3p was confirmed by luciferase reporter gene assay.ResultsThe overexpression of LINC01128 is associated with TNM stage and lymph node metastasis in CRC patients. Silencing LINC01128 inhibited the proliferation and metastasis of CRC cells. In addition, LINC01128 directly targeted and negatively regulated the miR-363-3p expression, while miR-363-3p inhibitor restored the inhibitory function of LINC01128.ConclusionAs an independent prognostic factor of CRC, upregulation of LINC01128 predicts poor prognosis and accelerates tumor deterioration through miR-363-3p.

TRF-33-P4R8YP9LON4VDP inhibits gastric cancer progression via modulating STAT3 signaling pathway in an AGO2-dependent manner.

It has been demonstrated that tRNA-derived small RNAs (tsRNAs) perform essential functions in the pathophysiology of cancer. In this study, we focused on the possible mechanisms of tRF-33-P4R8YP9LON4VDP (tRF-33) underlying the development of gastric malignancy. In total, 454 tissue samples with different gastric mucosal lesions were collected. The tRF-33 expression level in different cohorts was determined, and its value for diagnostic efficiency and prognosis evaluation were assessed. Cell proliferation assays, Transwell assay, flow cytometry, and xenotransplantation model were used to evaluate its effect on gastric cancer cells. The molecular mechanism was verified by fluorescence in situ hybridization, dual luciferase assay, Western blot, and RNA binding protein immunoprecipitation. The results showed that the expression of tRF-33 exhibited a gradual modification from normal control samples to gastritis tissues, early and latent stage of gastric cancer tissues. Consequently, tRF-33 holds significant potential as a predictive and diagnostic biomarker for gastric malignancy. Over-expression of tRF-33 inhibited gastric cancer cell progression and metastatic viability, and induced cell apoptosis. Tumorigenicity in nude mice showed the suppressive characteristics of tRF-33. Mechanistic investigation revealed that tRF-33 exerted silencing on STAT3 mRNA via binding to AGO2. In conclusion, tRF-33 exhibited values in diagnosing gastric cancer and evaluating its prognosis, and suppressed tumor cell viability by inhibiting STAT3 signaling pathway. The schematic mechanisms underlying tRF-33 regulating gastric cancer occurrence. tRF-33 binds to AGO2 proteins and then negatively regulates STAT3 expression through targeting its 3'UTR. The downregulated expression of STAT3 results in the decrease of STAT3 and p-STAT3 and further blocks the transcription of the downstream genes and finally inhibits the gastric cancer occurrence. MMP-9, matrix metalloproteinase-9; Bcl-2, B-cell lymphoma-2; STAT3, signal transducer and activator of transcription 3; UTR, untranslated region.

#1522 Comparative analysis of clinical and pathological traits in IgA nephropathy with nephrotic range proteinuria based on serum albumin level

Abstract Background and Aims Presently, the clinical outcomes associated with IgA nephropathy exhibiting heavy proteinuria and the potential correlation between decreasing serum albumin levels and adverse prognosis have not been conclusively established. The present study was designed to elucidate the clinical and pathological characteristics of IgA nephropathy patients who present with nephrotic-range proteinuria, particularly in relation to serum albumin levels. Method This retrospective cohort study was conducted using data from biopsy-confirmed IgA nephropathy patients presenting with nephrotic-range proteinuria between 2017 and 2022 from eight university-affiliated hospitals in South Korea. Patients were stratified into two groups based on a serum albumin level of 3.0 g/dl. The study involved a comparative assessment of clinical and pathological characteristics across these two groups, as well as an evaluation of clinical prognosis with respect to the end-stage kidney disease (ESKD). Results The analysis included a total of 127 patients. Of these, 86 patients had a serum albumin level above 3.0 g/dl (designated as the preserved albumin group, or PA group), while 41 patients had levels below 3.0 g/dl (designated as the reduced albumin group, or RA group). The baseline characteristics of the two groups were found to be statistically similar. The mean age of the patients was 46.46 years, and 46.46% were male. In the laboratory findings, the RA group had significantly elevated erythrocyte sedimentation rate compared to the PA group. Additionally, total cholesterol and low-density lipoprotein-cholesterol levels were significantly higher in the RA group compared to the PA group. Proteinuria was observed to be significantly higher in the RA group. Pathological examinations demonstrated that in electron microscopy (EM) findings, the RA group exhibited a more pronounced diffuse foot process effacement. Over the course of one year, the trend in creatinine changes exhibited differences between the two groups over time (time x group interaction P = 0.002). Furthermore, it appeared that the reduction in the quantity of proteinuria was more substantial within the RA group (time x group interaction P = 0.001). During a median follow-up period of 25.22 months (ranging from 11.98 to 49.23 months), 14 patients (11.02%) in the PA group progressed to ESKD, compared with 10 patient (24.39 %) in the RA group. However, there was no statistically significant difference between the two groups in terms of progression to ESKD (P = 0.330). Conclusion In patients diagnosed with IgA nephropathy presenting with nephrotic-range proteinuria, a decline in serum albumin levels was associated with diffuse foot process effacement, and the decrease in serum albumin was not found to be associated with adverse prognosis.

Rapid identification and prognosis evaluation by dual-phase computed tomography angiography for stroke patients with a large ischemic region in the anterior circulation treated with endovascular thrombectomy.

To investigate the value of dual-phase head-and-neck computed tomography angiography (CTA) in assessing advantages and risks associated with mechanical thrombectomy for stroke with a large ischemic region in the anterior circulation within 6 h of onset. We retrospectively analyzed the data of patients with acute occlusion of the internal carotid artery or middle cerebral artery-M1 segment. Baseline dual-phase CTA was performed for collateral grading using the 4-point visual collateral score (0, 0% filling; 1, >0% and ≤50% filling; 2, >50 and <100% filling; 3, 100% filling). The rates of modified Rankin score (MRS) ≤ 3 at 90 days, any intracranial hemorrhage (ICH) within 48 h, malignant cerebral edema within 24 h, and all-cause 90-day mortality were analyzed. Among the 69 study patients, 15, 26, 17, and 11 patients had collateral grades of 0, 1, 2, and 3, respectively. At 90 days, the MRS was ≤3 in 0, 8.33, 29.41, and 36.36% of patients with grades 0, 1, 2, and 3, respectively. ICH incidence was 73.33, 57.69, 29.41, and 18.18% for grades 0, 1, 2, and 3, respectively, while the incidence of malignant brain edema was 100, 76.92, 35.29, and 0%, respectively. All-cause 90-day mortality was 53.33% for grade 0 and 30.77% for grade 1; no deaths occurred at grades 2 and 3. Collateral grading based on dual-phase CTA enables simple and rapid preoperative evaluation prior to mechanical thrombectomy for acute anterior-circulation stroke with a large ischemic focus, particularly for patients presenting within the 6-h time window.

Clinical experience in a 46-year-old male patient with tuberculous meningitis: Case Report

Introduction: Tuberculosis (TB) is one of the most common cause of death from a single infectious agent. Tuberculosis is primarily a disease of the lungs, but it can also affect other parts of the body and cause extrapulmonary tuberculosis (EPTB). Approximately 5 % of all cases of EPTB are tuberculous meningitis (TMB), caused by the spread of Mycobacterium tuberculosis in the meninges and cerebrospinal fluid (CSF). MTB is the most devastating form of tuberculosis and continues to cause high morbidity and mortality, with approximately 50 % of patients dying or suffering neurological sequelae and complications. The aim of the present study is to learn more about the etiologic, clinical and diagnostic presentation of this pathology. Case report: we present a 46-year-old male patient who reports productive cough of approximately 9 months of evolution with presence of diaphoresis, no evidence of weight loss, 15 days ago the patient reported cough accompanied by hemoptysis, reason for which he went to the nearest health center. His evolution was torpid and his tuberculosis was complicated to tuberculous meningitis where compatible signs and symptoms were evidenced, and immediate treatment was started with isoniazid, rifampicin, pyrazinamide, ethambutol and later four months with isoniazid and rifampicin. Conclusions: the rapid diagnosis of MTB requires an understanding and a joint analysis of the clinical, radiological and laboratory findings of our infected and uninfected patients and the evaluation of prognoses

Multiple Sclerosis: From the Application of Oligoclonal Bands to Novel Potential Biomarkers

Multiple sclerosis is a chronic immune-mediated disorder of the central nervous system with a high heterogeneity among patients. In the clinical setting, one of the main challenges is a proper and early diagnosis for the prediction of disease activity. Current diagnosis is based on the integration of clinical, imaging, and laboratory results, with the latter based on the presence of intrathecal IgG oligoclonal bands in the cerebrospinal fluid whose detection via isoelectric focusing followed by immunoblotting represents the gold standard. Intrathecal synthesis can also be evidenced by the measurement of kappa free light chains in the cerebrospinal fluid, which has reached similar diagnostic accuracy compared to that of oligoclonal bands in the identification of patients with multiple sclerosis; moreover, recent studies have also highlighted its value for early disease activity prediction. This strategy has significant advantages as compared to using oligoclonal band detection, even though some issues remain open. Here, we discuss the current methods applied for cerebrospinal fluid analysis to achieve the most accurate diagnosis and for follow-up and prognosis evaluation. In addition, we describe new promising biomarkers, currently under investigation, that could contribute both to a better diagnosis of multiple sclerosis and to its monitoring of the therapeutic treatment response.

Hypermethylation of the Gene Body in SRCIN1 Is Involved in Breast Cancer Cell Proliferation and Is a Potential Blood-Based Biomarker for Early Detection and a Poor Prognosis.

Breast cancer is a leading cause of cancer mortality in women worldwide. Using the Infinium MethylationEPIC BeadChip, we analyzed plasma sample methylation to identify the SRCIN1 gene in breast cancer patients. We assessed SRCIN1-related roles and pathways for their biomarker potential. To verify the methylation status, quantitative methylation-specific PCR (qMSP) was performed on genomic DNA and circulating cell-free DNA samples, and mRNA expression analysis was performed using RT‒qPCR. The results were validated in a Western population; for this analysis, the samples included plasma samples from breast cancer patients from the USA and from The Cancer Genome Atlas (TCGA) cohort. To study the SRCIN1 pathway, we conducted cell viability assays, gene manipulation and RNA sequencing. SRCIN1 hypermethylation was identified in 61.8% of breast cancer tissues from Taiwanese patients, exhibiting specificity to this malignancy. Furthermore, its presence correlated significantly with unfavorable 5-year overall survival outcomes. The levels of methylated SRCIN1 in the blood of patients from Taiwan and the USA correlated with the stage of breast cancer. The proportion of patients with high methylation levels increased from 0% in healthy individuals to 63.6% in Stage 0, 80% in Stage I and 82.6% in Stage II, with a sensitivity of 78.5%, an accuracy of 90.3% and a specificity of 100%. SRCIN1 hypermethylation was significantly correlated with increased SRCIN1 mRNA expression (p < 0.001). Knockdown of SRCIN1 decreased the viability of breast cancer cells. SRCIN1 silencing resulted in the downregulation of ESR1, BCL2 and various cyclin protein expressions. SRCIN1 hypermethylation in the blood may serve as a noninvasive biomarker, facilitating early detection and prognosis evaluation, and SRCIN1-targeted therapies could be used in combination regimens for breast cancer patients.

Study on the therapeutic effects and prognosis evaluation of non-invasive ventilation in patients with chronic obstructive pulmonary disease with lung cancer.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory complication among the elderly, and its severity can escalate to respiratory failure as the disease progresses. To evaluate the application value of non-invasive ventilation in the clinical treatment of patients with COPD and lung cancer. This study assesses its therapeutic effects and its impact on patients' quality of life (QoL) as measured by the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale. A retrospective analysis was conducted on clinical data from 102 patients with COPD and lung cancer. Patients were divided into two groups: the control group (n= 48), who received conventional treatment, and the observation group (n= 54), who received non-invasive positive pressure ventilation (NIPPV) in addition to conventional treatment. Relevant indicators of curative effect, including blood gas indices, incidence of dyspnoea, improvements in mental health and appetite, and FACT-L QoL scores, were analysed at 2 weeks, 1 month, and 6 months post-treatment. At 2 weeks post-treatment, the observation group who had used NIPPV showed significant improvements in blood gas indices, dyspnoea, mental state and self-care ability compared with the control group (p< 0.05). At 1 month, these benefits persisted and included improved maintenance of body weight (p< 0.05). By 6 months, the observation group had a lower incidence of pulmonary encephalopathy (p< 0.05), and QoL, as measured by the FACT-L scale, improved significantly in the observation group but declined in the control group (p< 0.05). NIPPV demonstrates significant efficacy in treating COPD patients with lung cancer, particularly in enhancing curative effects and improving patients' QoL.

Involving logical clinical knowledge into deep neural networks to improve bladder tumor segmentation

Segmentation of bladder tumors from medical radiographic images is of great significance for early detection, diagnosis and prognosis evaluation of bladder cancer. Deep Convolution Neural Networks (DCNNs) have been successfully used for bladder tumor segmentation, but the segmentation based on DCNN is data-hungry for model training and ignores clinical knowledge. From the clinical view, bladder tumors originate from the mucosal surface of bladder and must rely on the bladder wall to survive and grow. This clinical knowledge of tumor location is helpful to improve the bladder tumor segmentation. To achieve this, we propose a novel bladder tumor segmentation method, which incorporates the clinical logic rules of bladder tumor and bladder wall into DCNNs to harness the tumor segmentation. Clinical logical rules provide a semantic and human-readable knowledge representation and are easy for knowledge acquisition from clinicians. In addition, incorporating logical rules of clinical knowledge helps to reduce the data dependency of the segmentation network, and enables precise segmentation results even with limited number of annotated images. Experiments on bladder MR images collected from the collaborating hospital validate the effectiveness of the proposed bladder tumor segmentation method.

Auxiliary diagnosis and prognosis evaluation of KIF4A, RAD51AP1 and CDKN3 in esophageal cancer

To investigate the expression of mRNA in esophageal cancer (ESCA) tissues and its potential and diagnostic and prognostic value by high-throughput sequencing data. Using the Cancer Genome Atlas Program (TCGA) database in USA by integrative bioinformatics analysis methods, the gene expression profiles and clinical data of 173 patients with ECSA were collected. The mRNA expression levels in ESCA tissue and para-cancerous tissue samples were analyzed using DESeq2, edgeR and limma to screen the differentially expressed genes (DEGs). DEGs-related protein network diagrams were drawn. GO and KEGG function enrichment analysis were performed and the hub genes were screened and the survival analysis of hub genes was analyzed. Genes related to the prognosis of ESCA were selected and their prognostic value in ESCA was analyzed. Finally, the receiver operating characteristic curve was drawn to evaluate its diagnostic value. The results showed that using TCGA cancer data, a total of 620 up-regulated DEGs and 668 down-regulated DEGs with significant differential expression between ESCA and para-cancerous tissues were screened. DEGs were mainly involved in receptor complexes, ubiquitin ligase complexes, etc., playing GTPase activity, phospholipid binding, and other molecular functions, and participating in the regulation of intracellular substance transport, small molecule metabolism, and other biological processes. Protein functional enrichment analysis showed that these proteins were mainly enriched in the IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, Epstein-Barr virus infection, neutrophil extracellular trap formation, and other pathways involved in the formation and development process of ESCA. Survival analysis showed that the overall survival rate of ESCA patients with high expression of KIF4A, RAD51AP1, and CDKN3 was significantly shortened, and the difference was statistically significant (P<0.05). Furthermore, the areas under the curve (AUC) of KIF4A, RAD51AP1, and CDKN3 for diagnosing esophageal cancer were 0.956, 0.951 and 0.979, respectively, with sensitivities and specificities both exceeding 80%. Additionally, ROC results of the combined diagnostic model of these three genes showed an AUC of 0.979, with sensitivities and specificities of 0.914 and 1, respectively. This indicates that KIF4A, RAD51AP1 and CDKN3 have individual or combined auxiliary diagnostic value for ESCA. In conclusion, KIF4A, RAD51AP1 and CDKN3 have high diagnostic efficiency for ESCA, and their increased expression is closely related to the prognosis, suggesting that these three genes could be used as auxiliary diagnostic and prognostic factors for ESCA.

Bronchoalveolar Lavage Fluid Microbiota is Associated with the Diagnosis and Prognosis Evaluation of Lung Cancer

Bronchoalveolar Lavage Fluid Microbiota is Associated with the Diagnosis and Prognosis Evaluation of Lung Cancer

Abstract PO5-06-11: RPL27A promotes the growth and metastasis of triple negative breast cancer by regulating Ribosome biogenesis

Abstract Background: Ribosome is a complex structure in cells for protein synthesis. It has been considered always have a constant composition. Recent studies have revealed that the Ribosome composition of tumor cells is heterogeneous. The Ribosome protein composition, post-translational modification, rRNA modification, and rRNA variants can lead to the existence of specialized "onco-ribosomes" in tumor cells, which regulates the rate of translation and protein synthesis, and can affect the occurrence and development of tumors significantly. The abnormal expression of multiple Ribosome proteins in triple-negative breast cancer may be the target of its diagnosis and treatment, also, an independent factor in prognosis evaluation. Methods: To learn the expression levels of Ribosome biogenesis related genes in normal breast cells and abnormal breast cells with different pathological subtypes of breast cancer, the following studies have been done: 1. Bioinformatics analysis on TCGA database and single-cell sequencing data; 2. IHC detection on TNBC tissue and adjacent tissues; 3. Determine the expression level of RPL27A in TNBC cells, and analyze the correlation between the expression of RPL27A and clinical information of patients. To explore the effect of RPL27A on Ribosome biogenesis, protein synthesis and other signaling pathways through Proteomics and molecular biology experiments have been designed and tested. The effects of RPL27A on malignant biological behaviors such as proliferation, migration, infiltration, and clonal formation of TNBC cells were studied through cell biology experiments and mouse experiments. Results: The analysis of TCGA database and single-cell sequencing data showed that the RPL27A was significantly increased in TNBC group. Immunohistochemical experiments showed that RPL27A was highly expressed in TNBC tissue and was impressively positively correlated with tumor size, lymph node metastasis, and bone metastasis. There was significantly negatively correlated with overall survival (OS) and disease free survival (DFS). It can be an independent factor for evaluating the prognosis of TNBC. By knocking out RPL27A in TNBC cell line, label free proteomics analysis showed that Ribosome biogenesis, protein synthesis, cell cycle regulation and other signaling pathways were obviously down regulated. Cell biology experiments have implied that the high expression of RPL27A in TNBC promotes cell proliferation, enhances cell migration, infiltration, and cloning ability, leads to more malignant biological behavior of tumor cells. Further research demonstrates that the high expression of RPL27A in TNBC significantly activated the EIF3C signal, cause changes in the composition of Ribosome in TNBC cells, promoted the formation of "onco-ribosomes", and distinctly increased the rate of protein synthesis. The study of PDX mice and Organoid showed that the knock out of RPL27A significantly reduced the growth rate and transfer ability of TNBC. Conclusion: The obvious over expressing of RPL27A in TNBC, which can significantly promote the growth and metastasis of tumor cells by influencing the Ribosome biogenesis process. Citation Format: Weipeng Zhao, Jingyi Zhang, Ye Zhu, Xin Yang, Xichuan Li. RPL27A promotes the growth and metastasis of triple negative breast cancer by regulating Ribosome biogenesis [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 PO5-06-11.

Elevated serum homocysteine levels associated with poor recurrence-free and overall survival in patients with colorectal cancer

This study aimed to evaluate the significance of homocysteine (HCY) levels in predicting recurrence-free survival (RFS) and overall survival (OS) in colorectal cancer (CRC) patients. This retrospective study involved 1272 CRC patients. The risk of mortality increased with increasing HCY levels in CRC patients. The optimal HCY cutoff value in CRC patients was 15.2 μmol/L. The RFS (45.8% vs. 60.5%, p < 0.001) and OS (48.2% vs. 63.2%, p < 0.001) of patients with high HCY levels were significantly lower than those of patients with low HCY levels. Patients with high HCY levels were older, male, had large tumours, high carcinoembryonic antigen (CEA) levels, and long hospital stays, and incurred high hospitalisation costs. Multivariate analysis showed that when HCY levels exceeded 15.2 μmol/L, the risk of adverse RFS and OS increased by 55.7% and 61.4%, respectively. Subgroup analysis showed that HCY levels could supplement CEA levels and pathological staging. We constructed HCY-based prognostic nomograms, which demonstrated feasible discrimination and calibration values better than the traditional tumour, node, metastasis staging system for predicting RFS and OS. Elevated serum HCY levels were strongly associated with poor RFS and OS in CRC patients. HCY-based prognostic models are effective tools for a comprehensive evaluation of prognosis.

Abstract PO3-08-05: Prognostic value of multigene test to the patients with Hormone receptor-positive, HER2-negative breast cancer based on special histologic subtypes

Abstract Background: Special histologic subtypes of breast cancer, including mucinous and tubular, account for 25% of all invasive breast cancers. Multigene tests (MGT) play a crucial role in guiding adjuvant chemotherapy and predicting prognosis for the patients with Hormone receptor-positive HER2-negative breast cancer. This research aims to examine the results of multigene tests for special histologic subtype patients and review the prognosis of each group. Methods: A retrospective analysis was conducted on data from 133 patients with special histologic subtypes of breast cancer who underwent surgery at Severance Hospital between November 2013 and December 2022. Each patient underwent one type of MGT, including Oncotype Dx, MammaPrint, or EndoPredict. Patients were grouped in two groups according to histologic types, based on WHO classification. Favorable types consist of type A mucinous carcinoma, pure tubular carcinoma, invasive solid papillary carcinoma, encapsulated papillary carcinoma with invasion, invasive cribriform carcinoma, secretory carcinoma, and invasive carcinoma with apocrine differentiation. Unfavorable types included type B mucinous carcinoma, mucinous carcinoma with micropapillary feature or neuroendocrine differentiation, mixed IDC, ILC or invasive micropapillary carcinoma, mixed invasive solid papillary carcinoma, mixed invasive papillary carcinoma, and mixed invasive cribriform carcinoma with IDC. Results: Patients with favorable types accounted for 42.86% (57 patients), while patients with unfavorable types accounted for 57.14% (76 patients). Patients with unfavorable histologic subtypes of breast cancer tended to have a higher incidence of high-risk results in MGT, as well as a greater prevalence of multiple (multifocal, multicentric) cancer and higher histologic grade. In multivariate analysis using logistic regression, unfavorable types showed a significantly high ratio of having high risk on MGT compared to the favorable type (OR = 4.327, 95% CI 1.210 – 15.475, p-value = 0.024). Moreover, overall survival in unfavorable histologic types showed a statistically significant difference between high-risk and low-risk in Kaplan-Meier survival analysis (p-value = 0.001). Conclusions: Unfavorable subtypes have shown a significantly higher-risk result of MGT, and patients with unfavorable types of breast cancer and high-risk MGT results have exhibited the worst prognosis. Consequently, we can suggest that MGT can be used as a prognosis evaluation tool for certain special subtypes of breast cancer and further utilized to aid in treatment decisions. Citation Format: Seung Hye Yang, Jee Hyun Ahn, Suk Jun Lee, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong Woo Park, Seho Park. Prognostic value of multigene test to the patients with Hormone receptor-positive, HER2-negative breast cancer based on special histologic subtypes [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 PO3-08-05.

Abstract PO3-14-04: Prognostic value of systemic inflammatory markers in neoadjuvant chemotherapy for breast triple negative cancer with pembrolizumab: development of a nomogram

Abstract Introduction: Systemic inflammatory markers derived from peripheral blood cells, such as the neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), have shown promise as prognostic markers for various cancer types. Inflammation plays a crucial role in cancer development, progression, metastasis, and resistance to treatment. However, only a few preoperative biomarkers have been identified as independent prognostic markers. Systemic inflammatory markers offer a reliable and easily accessible approach for prognosis evaluation. Materials and Methods: This study evaluated two groups of patients who received neoadjuvant chemotherapy for triple-negative breast cancer outside of clinical trials. The first group underwent neoadjuvant chemotherapy in 2021 with the EC X4 and weekly paclitaxel regimen, whereas the second group received neoadjuvant chemotherapy in 2022 following the KEYNOTE-522 study protocol with pembrolizumab. A total of 44 patients were included, with 23 patients in the pembrolizumab group. The NLR was defined as the absolute blood neutrophil count divided by the absolute lymphocyte count, and the derived neutrophil/lymphocyte ratio (dNLR) was defined as the absolute neutrophil count divided by the derived lymphocyte count (absolute leukocyte count —neutrophil count). The PLR was defined as the absolute platelet count divided by the absolute lymphocyte count. The LMR was defined as the absolute lymphocyte count divided by the absolute monocyte count. The association between systemic inflammatory markers (NLR, dNLR, PLR, and LMR) and pathological complete response (pCR) was analyzed using statistical tests. Inflammatory markers were evaluated at the time of diagnosis, at the time of chemotherapy regimen change, and two weeks before surgery. The χ2 test or Fisher’s exact test was used to analyze the correlation between the inflammatory indices and clinicopathologic parameters. Student’s t-test was used to compare different groups of continuous parametric data. Results: The pCR rates were 67% in the standard therapy group and 87% in the pembrolizumab group. There were no significant differences in other clinical characteristics between the two groups. The NLR, dNLR, PLR, and LMR at 6 months showed statistically significant differences compared to baseline levels. This difference was more evident in patients undergoing pembrolizumab therapy. ROC curves for the pembrolizumab group demonstrated an area under the curve (AUC) of 0.737, indicating a strong correlation between these systemic inflammatory markers and pCR. Based on these data, a nomogram was constructed to predict the likelihood of achieving pCR in patients undergoing neoadjuvant pembrolizumab therapy. Conclusion: This study highlights the potential of systemic inflammatory markers as prognostic indicators in patients with TNBC undergoing neoadjuvant chemotherapy. The significant differences observed in the pembrolizumab group and the high AUC of the ROC curves suggest the utility of these markers in predicting treatment response. The developed nomogram provides a practical tool for clinicians to estimate the probability of pCR based on NLR, dNLR, PLR, and LMR. Further research and validation are required to confirm the clinical utility of these markers in larger patient cohorts. Nomogram –insert figure image– ROC curve –insert figure image– Citation Format: Filippo Giovanardi, Giancarlo Bisagni, Elisa Gasparini, Alessandra Bologna, Roberto Di Cicilia, Gabriella Moretti, Claudia Degli Esposti, Carmine Pinto. Prognostic value of systemic inflammatory markers in neoadjuvant chemotherapy for breast triple negative cancer with pembrolizumab: development of a nomogram [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 PO3-14-04.

The therapeutic effect and targets of herba Sarcandrae on breast cancer and the construction of a prognostic signature consisting of inflammation-related genes

BackgroundThe prevalence of breast cancer (BRCA), which is common among women, is on the rise. This study applied network pharmacology to explore the potential mechanism of action of herba sarcandrae in BRCA and construct a prognostic signature composed of inflammation-related genes. MethodsThe active ingredients of herba sarcandrae were screened using the SymMap, TCMID, and TCMSP platforms, and the molecular targets were determined in the UniProt database. The “drug-active compound-potential target” network was established with Cytoscape 3.7.2. The molecular targets were subjected to disease ontology, gene ontology (GO), and Kyoto Encyclopedia of Genes (KEGG) analyses. AutoDock software was used for molecular docking. Differentially expressed genes (DEGs) related to inflammation were obtained from the BRCA Cancer Genome Atlas (TCGA) database. In the training cohort, the univariate Cox regression model was applied to preliminarily screen prognostic genes. A multigene signature was built by the least absolute shrinkage and selection operator (LASSO) regression model, followed by validation through Kaplan‒Meier, Cox, and receiver operating characteristic (ROC) analyses. ResultsForty-one active compounds were identified, and 265 therapeutic targets for herba sarcandrae were predicted. GO enrichment results revealed significant enrichment of biological processes, such as response to xenobiotic stimuli, response to nutrient levels, and response to lipopolysaccharide. KEGG analysis revealed significant enrichment of pathways such as AGE-RAGE and chemical carcinogenesis receptor activation signaling pathways. In addition, the herbs Marc-Andre and rutin were shown to mediate BRCA cell proliferation and apoptosis via the interferon regulatory factor 1 (IRF1)/signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) pathway. Sixteen inflammatory signatures, including BST2, GPR132, IL12B, IL18, IL1R1, IL2RB, IRF1, and others, were constructed, and the risk score was found to be a strong independent prognostic factor for overall survival in BRCA patients. The 16-inflammation signature was associated with several clinical features (age, clinical stage, T, and N classifications) and could reflect immune cell infiltration in tumor microenvironments with different immune cells. ConclusionsHerba sarcandrae and rutin were shown to mediate BRCA cell proliferation and apoptosis via the IRF1/STAT3/PD-L1 pathway, and the 16-member inflammatory signature might be a novel biomarker for predicting BRCA patient prognosis, providing more accurate guidance for clinical treatment prognosis evaluation and having important reference value for individualized treatment selection.

Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p<.001). HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

An anoikis-related lncRNA signature may predict the prognosis, immune infiltration, and drug sensitivity in esophageal cancer

BackgroundEsophageal cancer (EC) is a prevalent malignancy with heterogeneous outcomes. This study explores the significance of anoikis-related long non-coding RNAs (lncRNAs) in EC, aiming to unravel their molecular roles and clinical implications. MethodsTranscriptome and clinical data were obtained from TCGA database for EC samples. We identified anoikis-related genes and lncRNAs by Pearson correlation analysis. The risk score model hinged on prognostic lncRNAs filtered from multiple steps. Risk scores were calculated using the derived formula, and categorized patients into low- and high-risk groups. Model robustness was assessed through Kaplan-Meier (KM) survival analysis and Receiver Operating Characteristic (ROC) curve, with clinical utility achieved via a constructed nomogram. We also explored the interplay between the risk score and immune cell infiltration, and investigated drug sensitivity. ResultsWe identified 2365 anoikis-related lncRNAs through co-expression analysis, including 1415 significant lncRNAs differentially expressed between normal and tumor samples. A risk score model was constructed from ten prognostic lncRNAs. The risk score model effectively stratified patients based on the median score, and its predictive capacity was validated through KM survival, ROC curve analyses, and the external GSE53622 dataset. The nomogram provided a practical tool for individualized prognosis evaluation. We unveiled significant correlations between specific immune cell subsets and the risk score. Eosinophils and common lymphoid progenitors exhibited positive associations, while endothelial cells and myeloid dendritic cells showed negative correlations. Drug sensitivity analysis revealed potential sensitive drugs for EC treatment that aligned with the risk subgroups. ConclusionThis study established an anoikis-related lncRNAs risk score model that may predict the prognosis, immune infiltration, and drug sensitivity in EC, in hope of facilitating tailored patient management.

Advances in non-invasive treatment of aortic diseases

The current clinical treatment methods for aortic diseases including aortic aneurysm, aortic dissection,etc.,are open surgery and endovascular surgery. Compared to traditional open surgery, endovascular surgery has the advantages of minimal trauma, fast recovery, fewer complications, and better prognosis, which gradually becomes the main trend in the treatment of aortic diseases. However, with the further development and long-term follow-up of endovascular treatment for aortic diseases, increasing evidence shows that in many cases, there are difficulties in the diagnosis of causes, decision-making of treatment timing, and lack of effective evaluation of treatment prognosis in endovascular treatments. Therefore, it is necessary to conduct in-depth research on non-invasive treatment including prevention, diagnosis, treatment, and prediction of aortic diseases. The non-invasive treatment of aortic disease is mainly applied to high-risk populations with aortic dissection, regulating key targets and mechanisms, and adopting drug intervention in advance to achieve the goal of controlling aortic dilation and preventing the occurrence of dissection. Conducting precise multi omics analysis to determine the optimal intervention timing and treatment strategy and targeting complications related to aortic disease or endovascular treatment for patients with a positive family history of aortic dilation or those who have developed aortic dissection. Precise regulation can be achieved to control the progression of aortic aneurysm and aortic dissection, delay or achieve long-term stable coexistence with aortic disease, and even reverse disease progression and achieve benign aortic remodelingthrough new intervention vectors. Ultimately achieving the ideal state of complete thrombosis and mechanized healing of the aortic aneurysm or aortic dissection false lumen.