Tumor Lymph Node Metastasis Research Articles

Association between blood inflammatory indicators and prognosis of papillary thyroid carcinoma: a narrative review.

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer, accounting for up to 85-90% of cases, with the best overall prognosis and mostly inert tumors. However, some tumors are aggressive, causing metastasis, recurrence, and other bad outcomes. Preoperative inflammation indices, such as lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII) in peripheral blood, have recently gained attention as nonspecific markers of inflammatory response in thyroid. In this study, we reviewed the interactions between preoperative inflammatory factors and outcomes in patients with PTC. This is a narrative review. We searched for English articles published between January 2014 and December 2023 on PubMed and Web of Science to identify how do these blood indicators affect the prognosis of patients with papillary thyroid cancer. All retrievable indicators that have predictive significance for the prognosis of PTC were included, and the prognosis mainly included tumor-node-metastasis (TNM) staging, survival rate, recurrence, clinical and pathological risk factors such as lymph node metastasis (LNM), etc. From the general evidence, the prognostic predictive value of cell count alone was unknown, and low LMR was usually associated with poor prognosis, high NLR and high platelet-to-lymphocyte ratio (PLR) usually indicated poor prognosis. These minimally invasive, low-cost, and easily obtainable blood indicators provide convenience for precise prognosis management of PTC patients, but many of the findings are conflicting and need to be validated by prospective studies that are more multi-sample, multi-centre and incorporate factors such as age that affect the immune response.

The EFNA4 gene is a potential prognostic biomarker in pancreatic cancer: a bioinformatics analysis.

Pancreatic cancer is a highly aggressive malignancy with poor prognosis, and there is an urgent need to understand its molecular mechanisms for early diagnosis and treatment. Despite surgical resection being the only effective treatment, most patients are diagnosed at an advanced stage, missing the optimal window for therapy. Identifying novel biomarkers is crucial for prognostic assessment, treatment planning, and early intervention. Ephrin A4 (EFNA4), a member of the receptor tyrosine kinase family, is involved in vascular and epithelial development via regulation of cell migration and rejection. However, the role of EFNA4 in pancreatic cancer has not been reported. Therefore, our study aimed to clarify the role of EFNA4 in pancreatic cancer through bioinformatics analysis and vitro experiments. The expression of EFNA4 and its potential value as a diagnostic and prognostic biomarker in pancreatic cancer was analyzed using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) database. According to the expression level of EFNA4, patients were divided into high expression group and low expression group, and the correlation between overall survival (OS) and disease-free survival (DFS) with different expression levels of EFNA4 and clinical parameters were analyzed. Subsequently, reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect EFNA4 expression. The proliferation, invasion, and cloning ability of the cells were detected via Cell Counting Kit 8 (CCK8), Transwell, and plate cloning assays, respectively. EFNA4 is highly expressed in pancreatic cancer, and upregulation of EFNA4 is associated with poor prognosis. In this study, EFNA4 expression was correlated with T stage and TNM (tumor-node-metastasis) stage of pancreatic cancer, and the median survival time and progression-free survival (PFS) were worse in those with high EFNA4 expression (394 days) than in those with low expression (525 days) [hazard ratio (HR): 1.47, 95% confidence interval (CI): 1.00-2.16, P=0.047]. In addition, EFNA4 was also found to be involved in the regulation of signal pathways such as cell adhesion, cyclic AMP, insulin secretion, pancreatic secretion, and protein digestion and absorption. In vitro experiments demonstrated that EFNA4 knockdown significantly inhibited the proliferation, cloning ability, and invasiveness of the PANC-1 and SW1990 pancreatic cancer cell lines. The abnormal expression of EFNA4 in pancreatic cancer is associated with poor prognosis. Knockout of EFNA4 gene could significantly inhibit the proliferation and invasion of pancreatic cancer cells. Therefore, EFNA4 may be one of the molecular targets for poor prognosis of patients with pancreatic cancer.

Development and external validation of a prognostic nomogram to predict survival in patients aged ≥60 years with pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC), which accounts for the vast majority of pancreatic cancer (PC), is a highly aggressive malignancy with a dismal prognosis. Age is shown to be an independent factor affecting survival outcomes in patients with PDAC. Our study aimed to identify prognostic factors and construct a nomogram to predict survival in PDAC patients aged ≥60 years. Data of PDAC patients aged ≥60 years were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox regression analysis was used to determined prognostic factors of overall survival (OS) and cancer-specific survival (CSS), and two nomograms were constructed and validated by calibration plots, concordance index (C-index) and decision curve analysis (DCA). Additionally, 432 patients from the First Affiliated Hospital of Wenzhou Medical University were included as an external cohort. Kaplan-Meier curves were applied to further verify the clinical validity of the nomograms. Ten independent prognostic factors were identified to establish the nomograms. The C-indexes of the training and validation groups based on the OS nomogram were 0.759 and 0.760, higher than those of the tumor-node-metastasis (TNM) staging system (0.638 and 0.636, respectively). Calibration curves showed high consistency between predictions and observations. Better area under the receiver operator characteristic (ROC) curve (AUC) values and DCA were also obtained compared to the TNM system. The risk stratification based on the nomogram could distinguish patients with different survival risks. We constructed and externally validated a population-based survival-predicting nomogram for PDAC patients aged ≥60 years. The new model could help clinicians personalize survival prediction and risk assessment.

Collecting routine and timely cancer stage at diagnosis by implementing a cancer staging tiered framework: the Western Australian Cancer Registry experience

BackgroundCurrent processes collecting cancer stage data in population-based cancer registries (PBCRs) lack standardisation, resulting in difficulty utilising diverse data sources and incomplete, low-quality data. Implementing a cancer staging tiered framework aims to improve stage collection and facilitate inter-PBCR benchmarking.ObjectiveDemonstrate the application of a cancer staging tiered framework in the Western Australian Cancer Staging Project to establish a standardised method for collecting cancer stage at diagnosis data in PBCRs.MethodsThe tiered framework, developed in collaboration with a Project Advisory Group and applied to breast, colorectal, and melanoma cancers, provides business rules – procedures for stage collection. Tier 1 represents the highest staging level, involving complete American Joint Committee on Cancer (AJCC) tumour–node–metastasis (TNM) data collection and other critical staging information. Tier 2 (registry-derived stage) relies on supplementary data, including hospital admission data, to make assumptions based on data availability. Tier 3 (pathology stage) solely uses pathology reports.FindingsThe tiered framework promotes flexible utilisation of staging data, recognising various levels of data completeness. Tier 1 is suitable for all purposes, including clinical and epidemiological applications. Tiers 2 and 3 are recommended for epidemiological analysis alone. Lower tiers provide valuable insights into disease patterns, risk factors, and overall disease burden for public health planning and policy decisions. Capture of staging at each tier depends on data availability, with potential shifts to higher tiers as new data sources are acquired.ConclusionsThe tiered framework offers a dynamic approach for PBCRs to record stage at diagnosis, promoting consistency in population-level staging data and enabling practical use for benchmarking across jurisdictions, public health planning, policy development, epidemiological analyses, and assessing cancer outcomes. Evolution with staging classifications and data variable changes will futureproof the tiered framework. Its adaptability fosters continuous refinement of data collection processes and encourages improvements in data quality.

Cyclin L1 participates in Adriamycin resistance and progression of osteosarcoma via PI3K/AKT-mTOR pathway.

Chemoresistance is a common and thorny problem in the treatment of osteosarcoma (OS), which obstructs the response of relapse or metastasis of OS to chemotherapy and leads to the unfavorable prognosis of OS patients. Cyclin L1 (CCNL1) is a non-canonical cyclin that plays an important role in the regulation of tumor cell proliferation and lymph node metastasis. In this work, we explored the impact of CCNL1 expression levels on proliferation, migration, and Adriamycin (ADM) resistance in OS and related mechanisms. We found that CCNL1 expression levels were significantly associated with clinical prognosis of patients with OS and CCNL1 could promote OS proliferation and migration. In addition, we also revealed that cellular CCNL1 was significantly increased in ADM-resistant OS cells and promoted ADM resistance. The PI3K/AKT-mTOR pathway is involved in CCNL1-mediated ADM resistance in OS. In summary, CCNL1 is involved in the progression of ADM resistance and OS through the PI3K/AKT-mTOR pathway, which will provide a new clue to the mechanism of ADM resistance and a potential target for the treatment of ADM-resistant OS.

Correlation between Neurotransmitters (Dopamine, Epinephrine, Norepinephrine, Serotonin), Prognostic Nutritional Index, Glasgow Prognostic Score, Systemic Inflammatory Response Markers, and TNM Staging in a Cohort of Colorectal Neuroendocrine Tumor Patients.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

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

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

Quantitative parameter analysis of pretreatment dual-energy computed tomography in nasopharyngeal carcinoma cervical lymph node characteristics and prediction of radiotherapy sensitivity

BackgroundTreatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor–node–metastasis stages. Moreover, end-of-treatment tumor regression is a reliable indicator of treatment sensitivity. This study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parameters could predict sensitivity to neck–lymph node radiotherapy in patients with NPC.MethodsOverall, 388 lymph nodes were collected from 98 patients with NPC who underwent pretreatment DECT. The patients were divided into complete response (CR) and partial response (PR) groups. Clinical characteristics and quantitative DECT parameters were compared between the groups, and the optimal predictive ability of each parameter was determined using receiver operating characteristic (ROC) analysis. A nomogram prediction model was constructed and validated using univariate and binary logistic regression.ResultsDECT parameters were higher in the CR group than in the PR group. The iodine concentration (IC), normalized IC, Mix-0.6, spectral Hounsfield unit curve slope, effective atomic number, and virtual monoenergetic images were significantly different between the groups. The area under the ROC curve of the DECT parameters was 0.73–0.77. Based on the binary logistic regression, a column chart was constructed using 10 predictive factors, including age, sex, N stage, maximum lymph node diameter, arterial phase NIC, venous phase NIC, λHU and spectral Hounsfield units at 70 keV. The area under the ROC curve value of the constructed model was 0.813, with a sensitivity and specificity of 85.6% and 81.3%, respectively.ConclusionQuantitative DECT parameters could effectively predict the sensitivity of NPC to radiotherapy. Therefore, DECT parameters and NPC clinical features can be combined to construct a nomogram with high predictive power and used as a clinical analytical tool.

A novel mitochondrial-related lncRNA signature mediated prediction of overall survival, immune landscape, and the chemotherapeutic outcomes for bladder cancer patients

ObjectiveTo develop a prognostic risk model for Bladder Cancer (BLCA) based on mitochondrial-related long non-coding RNAs (lncRNAs).MethodsTranscriptome and clinical data of BLCA patients were retrieved from the TCGA database. Mitochondrial-related lncRNAs with independent prognostic significance were screened to develop a prognostic risk model. Patients were categorized into high- and low-risk groups using the model. Various methods including Kaplan–Meier (KM) analysis, ROC curve analysis, Gene Set Enrichment Analysis (GSEA), immune analysis, and chemotherapy drug analysis were used to verify and evaluate the model.ResultsA mitochondrial-associated lncRNA prognostic risk model with independent prognostic significance was developed. High-risk group (HRG) patients exhibited significantly shorter survival periods compared to low-risk group (LRG) patients (P < 0.01). The risk score from the model was an independent predictor of BLCA prognosis, correlating with tumor grade, pathological stage, and lymph node metastasis (P < 0.05). The HRG showed significant positive correlations with high expressions of immune checkpoints (CTLA4, LAG3, PD-1, TIGIT, PD-L1, PD-L2, and TIM-3) and lower IC50 for chemotherapy drugs (cisplatin, docetaxel, paclitaxel, methotrexate, and vinblastine) (P < 0.001).ConclusionsThe mitochondrial-related lncRNA-based prognostic risk model effectively predicts BLCA prognosis and can guide individualized treatment for BLCA patients.

Exploration of the prognostic value of methylation regulators related to m5C in papillary thyroid carcinoma.

The incidence of papillary thyroid carcinoma (PTC) has increased significantly in recent years, and for patients with metastatic and recurrent PTC, the options for treatment currently available are insufficient. To date, the exact molecular mechanism underlying PTC is still not fully understood. 5-Methylcytosine (m5C) RNA methylation is associated with the prognosis of a variety of tumors. However, the molecular mechanisms and biomarkers associated with m5C in the diagnosis, treatment, and prognosis of this disease have not been fully elucidated. Ten m5C regulators with significantly different expression levels were included in this study. Immune infiltration analysis revealed significant negative correlations between most of these regulators and regulatory T cells. TRDMT1, NSUN5, and NSUN6 had high weights and strong correlations in the protein-protein interaction network. Using gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis, 1489 differentially expressed genes were screened from The Cancer Genome Atlas messenger RNA matrix, indicating that these differentially expressed genes were significantly enriched in various pathways and functions related to cancers. Four m5C regulators, NSUN2, NSUN4, NSUN6, and DNMT3B, were screened as prognostic markers by least absolute shrinkage and selection operator regression analysis, and NSUN2 and NSUN6 were identified as risk factors for poor prognosis. We found that the prognostic prediction model constructed using the m5C regulators NSUN2, NSUN4, NSUN6, and DNMT3B showed good prognostic prediction ability and diagnostic ability. This model was applied to predict the survival probability of patients with PTC, the prediction ability of 5-year survival was the best. The multi-factor prognostic prediction model combined with the tumor node metastasis stage and risk score grouping showed better prognostic predictive power.

LINC00662 Promotes Aggressive Traits by Modulating OCT4 Expression through miR-335-5p in Gallbladder Cancer Cells.

Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including cancer. Long intergenic non-protein-coding RNA 662 (LINC00662) has been reported to be involved in different cancers, including colorectal, prostate, and breast cancer. However, its role in gallbladder cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133+/CD44+ cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial-mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC.

Expression of p53 and ki-67 in Breast Carcinomas and Their Association with Histopathological Type, Grade, and Stage

Background &amp; objective: Recently many laboratories are evaluating the usefulness of determining p53, and Ki67 proliferation activities using immunohistochemical techniques in cancer. Although the available studies suggest that these factors might help make treatment decisions in cancer patients, their clinical usefulness is still controversial. The present study was undertaken to see the expression of p53 and Ki-67 in breast carcinoma and their associations with histopathological variables. Methods: This cross-sectional analytical study was conducted in the Department of Pathology, in collaboration with the Department of Surgery, Rajshahi Medical College Hospital and the Department of Pathology, Bangobandhu Sheikh Mujib Medical University (BSMMU), Dhaka over a period of one and a half year from July 2018 to December 2019. Resected specimens of breast tissue, histopathologically confirmed as breast carcinoma, were the study population. Histological grading of breast carcinoma was done according to Nottingham modification of the Bloom-Richardson system, while staging was done using Tumor-Node-Metastasis (TNM) classification of malignant tumors, as recommended by the Union for International Cancer Control (UICC). The Ki67 and p53 expressions were assessed by immunohistochemistry. Based on the Ki67 labeling index (Ki67-LI), the patients were divided into two groups – Ki 67 &gt; 30% (considered as over-expressed) and ≤ 30% (considered as less expressed). Likewise, p53 immuno-expression was grouped as over-expressed (score ≤ 8) and low-expressed (score &gt; 8). The histological grade, type, and stage were then compared between patients with tumours of high and low proliferating activities to find the associations of Ki67 and p53 with tumor grade, type, and stage. Result: In the present study, almost three-quarters (74%) of the specimen of the breast had high Ki67-LI and 26% intermediate and low Ki67-LI. The p53 was found to be highly expressed in the majority (86%) of the cases. Analyses of the association of biomarkers with histological grade, stage, and type revealed that advanced-stage breast cancers (Stage-IIIA) were more likely to be associated with high Ki67-LI than the early-stage breast cancers (Stage-IIA and Stage-IIB) (p = 0.023). Poorly differentiated (G3) carcinoma also more often tends to be associated with high Ki67-LI than with low and intermediate Ki67-LI (p = 0.066). Likewise, stage IIIA tumors and poorly differentiated carcinoma were also considerably higher in the p53 over-expressed group (23.3%) than in the low p53 expression group (14.3%) (p = 0.023). Conclusion: The study concluded that a substantial proportion of breast carcinomas demonstrates high Ki67-LI. The p53 overexpression is also found in the majority (86%) of the breast carcinoma cases. Both Ki67 and p53 proliferation activities show their significant presence in high-grade and advanced-stage tumours. Ibrahim Card Med J 2023; 13 (1&amp;2): 11-18

Multi-Center Assessment of Lymph-Node Density and Nodal-Stage to Predict Disease-Specific Survival in Patients with Bladder Cancer Treated by Radical Cystectomy.

Prognostic tools in pathological-node (pN) patients after radical cystectomy (RC) are needed. To evaluate the prognostic impact of lymph node (LN)-density on disease-specific survival (DSS) in patients with bladder cancer (BC) undergoing RC with pelvic lymph node dissection. We analyzed a multi-institutional cohort of 1169 patients treated with upfront RC for cT1-4aN0M0 urothelial BCat nine centers. LN-densitywas calculated as the ratio of the number of positive LNs×100% to the number of LNs removed. The optimal LN-density cut-off value was defined by creating a time-dependent receiver operating characteristic (ROC) curve in pN patients. Univariable and multivariable Cox' regression analyses were used to assess the effect of conventional Tumor Nodes Metastasis (TNM) nodal staging system, LN-density and other LN-related variables on DSS in the pN-positive cohort. Of the 1169 patients, 463 (39.6%) patients had LN-involvement. The area under the ROC curve was 0.60 and the cut-off for LN-density was set at 20%, 223 of the pN-positive patients (48.2%) had a LN-density ≥ 20%. In multivariable models, the number of LN-metastases (HR 1.03, p = 0.005) and LN-density, either as continuous (HR 1.01, p = 0.013) or as categorical variable (HR 1.37, p = 0.014), were independently associated with worse DSS, whereas pN-stage was not. LN-density ≥ 20% was an independent predictor of worse DSS in BC patients with LN-involvement at RC. The integration of LN-density and other LN-parameters rather than only conventional pN-stage may contribute to a more refined risk-stratification in BC patients with nodal involvement.

Clinicopathological significance and prognostic analysis of p21 and EGFR in colorectal cancer: a retrospective analysis on 12 319 cases in China

AimsColorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are crucial for patients with CRC. This study aims...

ПАРАНЕОПЛАСТИЧЕСКИЙ НЕВРОЛОГИЧЕСКИЙ СИНДРОМ У РЕБЕНКА С НЕЙРОБЛАСТОМОЙ: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

Paraneoplastic syndromes are of particular difficulties in establishing a timely diagnosis of a malignant tumor esp. in cases when the decease development is occurred chronologically much earlier than the appearance of its specific symptoms and the neoplasm growth’s first signs. And the clinical manifestation can be represented solely by an isolated clinic of paraneoplastic syndrome, which in its turn is much alike the symptoms of the paraneoplastic neurological syndrome (PNS). Authors represent a clinical case of a severe PNS coupled with the central nervous system (CNS) lesion, mainly the cerebellum, which was manifested clinically by ataxia, tremor, myoclonus, dysartria, cognitive and mental impairment and psychotic disorders, which in its turn had delayed the timely diagnosis of neuroblastoma (left-sided intermixed adrenal ganglioneuroblastoma with metastatic tumors in ipsilateral lymph nodes and paranephric fat, deletion 1q, deletion 1p36 and MYCN amplification - all negative and INSS stage 2B) in a 5 y/o male patient. No ‘classical’ opsoclonus-myoclonus was a matter of diagnosis due to the opsoclonus absence during the whole disease course. This clinical case observation publication is having a practical purpose of pinning attention to paraneoplastic syndromes among practitioners of wide spectrum: neurologists, infectionists and pediatricians.

Construction of a nomogram for predicting HNSCC distant metastasis and identification of EIF5A as a hub gene

Patients with distant metastasis of head and neck squamous cell carcinoma (HNSCC) often have a poor prognosis. However, early diagnosis of distant metastasis is challenging in clinical practice, and distant metastasis is often only detected in the late stages of tumor metastasis through imaging techniques. In this study, we utilized data from HNSCC patients collected from the TCGA database. Patients were divided into distant metastasis and nonmetastasis groups based on the tumor–node–metastasis (TNM) stage. We analyzed the differentially expressed genes between the two groups (DM/non-M DEGs) and their associated lncRNAs and generated a predictive model based on 23 lncRNAs that were significantly associated with the occurrence of distant metastasis in HNSCC patients. On this basis, we built a nomogram to predict the distant metastasis of HNSCC patients. Moreover, through WGCNA and Cytoscape software analysis of DM/non-M DEGs, we identified the gene most closely related to HNSCC distant metastasis: EIF5A. Our findings were validated using GEO data; EIF5A expression was significantly increased in the tumor tissues of HNSCC patients with distant metastasis. We then predicted miRNAs that can directly bind to EIF5A via the TargetScan and miRWalk websites, intersected them with differentially expressed miRNAs in the two groups from the TCGA cohort, and identified the only overlapping miRNA, miR-424; we predicted the direct binding site of EIF5A and miR-424 via the miRWalk website. Immunohistochemistry further revealed high expression of EIF5A in the primary tumor tissue of HNSCC patients with distant metastasis. These results provide a new perspective for the early diagnosis of distant metastasis in HNSCC patients and the study of the mechanisms underlying HNSCC distant metastasis.

Biomarker conversion from primary breast cancer to synchronous axillary lymph node metastasis and neoadjuvant therapy response: a single-center analysis

PurposeThe biomarker characteristics of breast cancer plays an important role in predicting treatment sensitivity. The aim of the present study was to compare immunohistochemical profiles (ER, PR, HER2, and Ki67) between the primary tumor and synchronous axillary lymph node metastasis and investigate the subsequent effects on neoadjuvant therapy response.MethodsA total of 358 patients with pathologically confirmed synchronous axillary lymph node metastasis at first diagnosis and treated by neoadjuvant therapy at Peking University First Hospital from January 1, 2013 to December 31, 2022 were included in this retrospective study. Clinicopathologic data, especially receptor status in primary and metastatic foci, was collected for each case.ResultsChange of ER, PR, HER2, and Ki67 expression was observed in 5.9%, 8.7%, 12.6%, and 17.3% of patients, respectively. HR discordance was observed more frequently when the ER status (p = 0.023) or PR status (p = 0.010) of primary tumor was negative, while HER2 discordance seemed to be more frequent when the HER2 status of primary tumor was HER2-0 or HER2-low (p < 0.001). Patients with loss of HR-positivity (positive to negative) responded to neoadjuvant chemotherapy better compared to those with stable positive HR expression (50% vs. 11.1%, p = 0.0017). A significantly decrease in pCR rate was observed in patients with unstable HER2 status, but not in the HER2-0/HER2-low subgroup.ConclusionReceptor discordance between primary tumor and synchronous axillary LNM appears to already exist before any anti-tumor therapy. This instability has limited clinical impact on the choice of neoadjuvant therapy at current stage, but further investigation is warranted with the incremental application of endocrine drugs and ADCs in neoadjuvant therapy.

Multi-regional sequencing reveals the genetic and immune heterogeneity of non-cancerous tissues in gastric cancer.

Gastric cancer (GC) is one of the most heterogeneous tumors. However, research on normal tissue adjacent to the tumor (NAT) is very limited. We performed multi-regional omics sequencing on 150 samples to assess the genetic basis and immune microenvironment in NAT and matched primary tumor or lymph node metastases. NATs demonstrated different mutated genes compared with GC, and NAT genomes underwent independent evolution with low variant allele frequency. Mutation profiles were predominated by aging and smoking-associated signatures in NAT instead of signatures associated with genetic instability. Although the immune microenvironment within NATs shows substantial intra-patient heterogeneity, the proportion of shared TCR clones among NATs is five times higher than that of tumor regions. These findings support the notion that subclonal expansion is not pronounced in NATs. We also demonstrated remarkable intra-patient heterogeneity of GCs and revealed heterogeneity of focal amplification of CD274 (encoding PD-L1) that leads to differential expression. Finally, we identified that monoclonal seeding is predominant in GC, which is followed by metastasis-to-metastasis dissemination in individual lymph nodes. These results provide novel insights into GC carcinogenesis. © 2024 The Pathological Society of Great Britain and Ireland.

High-expression of V-domain Imuunoglobulin Suppressor of T-cell Activation (VISTA) Is Correlated with Advanced Pathological Features in Patients with Pancreatic Ductal Adenocarcinoma.

V-domain Imuunoglobulin suppressor of T-cell activation (VISTA) seems a promising immune checkpoint target in cancer treatment; however, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Herein, 29 fresh PDAC tissue samples were used to evaluate the mRNA expression level of VISTA by real-time polymerase chain reaction (PCR). Besides, 40 formalin-fixed paraffin-embedded PDAC tissues were collected to evaluate VISTA protein expression by immunohistochemistry. Real-time PCR indicated that high expression of VISTA was significantly correlated with advanced stages of the cancer, based on the tumor/node/metastasis (TNM) stagingand tumor cell differentiation. Immunohistochemistry results also showed significant correlation of the elevated cytoplasmic expression of VISTA with advanced TNM stages, older age of the patients and was a worsening indicator, regarding the disease-specific survival. In conclusion, we found that the expression levels of VISTA can be a potential prognostic biomarker in PDAC patients and its elevated levels are correlated with poor prognostic outcomes.

Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer.

e16119 Background: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC)patients; therefore, establishing a new predictive stage is necessary.To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC. Methods: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed. The relationship between LNR and clinicopathological characteristics was analyzed. The survival analysis was performed using Kaplan–Meier survival curves and Cox regression model. Results: Number of metastatic LNs, tumor diameter, depth of tumor invasion, Borrmann type, serum tumor biomarkers, and tumor–node–metastasis (TNM) stage were correlated with LNR stage and N stage. Univariate analysis revealed that the factors affecting survival included tumor diameter, anemia, serum tumor biomarkers, vascular or neural invasion, combined resection, LNR stage, N stage, and TNM stage (all P &lt; 0.05). The median survival time for those with LNR0, LNR1, LNR2 and LNR3 stage were 61, 31, 23 and 17 mo, respectively, and the differences were significant ( P = 0.000). Anemia, tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis (all P &lt; 0.05). Conclusions: The new LNR stage is uniquely based on number of metastatic LNs, with significant prognostic value for locally advanced GRC, and could better differentiate overall survival, compared with N stage.