Metastasis Status Research Articles

Association between Toll-like receptor 2 rs4696483 and rs1898830 polymorphisms and the risk of triple-negative breast cancer

PurposeBreast cancer (BC) is heterogeneous in clinical manifestation, of which the triple-negative (TNBC) subtype is the most aggressive. This study examines the associations between Toll-Like Receptor (TLR)-2 polymorphisms and the susceptibility to BC and TNBC. MethodsGenotyping of TLR-2 rs1898830 and rs4696483 polymorphisms was done by real-time PCR in 488 women with BC (130 TNBC, 358 non-TNBC) and 476 cancer-free control women. ResultsThe minor allele frequency (MAF) of rs4696483 was significantly lower in BC cases compared to controls, and significantly lower frequencies of rs4696483 C/T and higher frequencies of rs1898830 G/G genotypes were seen in BC cases. Significantly higher MAF of rs4696483 and higher C/T and T/T rs4696483 genotypes frequencies were seen in TNBC than in non-TNBC cases. Considering the prevalent AC haplotype as a reference, 2-locus TLR-2 haplotype analysis did not identify any 2-locus TLR-2 haplotype associated with an altered risk of BC or TNBC. Positive associations of rs1898830 and rs4966483 were seen with the histological type in TNBC and negatively with distant metastasis and HR status in TNBC and non-TNBC rs1898830 carriers. In addition, rs4696483 was positively correlated with hormonotherapy and surgery in non-TNBC cases, while rs1898830 was negatively associated with hormonotherapy. Furthermore, rs1898830 was negatively and positively correlated with BMI in TNBC and TNBC cases, respectively, but positively with Ki-67 status. ConclusionsOur study highlights the association between TLR-2 genetic polymorphisms and BC and TNBC susceptibility, suggesting these variants' diagnostic/prognostic capacity in BC patients and patient subgroups.

Identification of a pro-protein synthesis osteosarcoma subtype for predicting prognosis and treatment

Osteosarcoma (OS) is a heterogeneous malignant spindle cell tumor that is aggressive and has a poor prognosis. Although combining surgery and chemotherapy has significantly improved patient outcomes, the prognosis for OS patients with metastatic or recurrent OS has remained unsatisfactory. Therefore, it is imperative to gain a fresh perspective on OS development mechanisms and treatment strategies. After studying single-cell RNA sequencing (scRNA-seq) data in public databases, we identified seven OS subclonal types based on intra-tumor heterogeneity. Subsequently, we constructed a prognostic model based on pro-protein synthesis osteosarcoma (PPS-OS)-associated genes. Correlation analysis showed that the prognostic model performs extremely well in predicting OS patient prognosis. We also demonstrated that the independent risk factors for the prognosis of OS patients were tumor primary site, metastatic status, and risk score. Based on these factors, nomograms were constructed for predicting the 3- and 5-year survival rates. Afterward, the investigation of the tumor immune microenvironment (TIME) revealed the vital roles of γδ T-cell and B-cell activation. Drug sensitivity analysis and immune checkpoint analysis identified drugs that have potential application value in OS. Finally, the jumping translocation breakpoint (JTB) gene was selected for experimental validation. JTB silencing suppressed the proliferation, migration, and invasion of OS cells. Therefore, our research suggests that PPS-OS-related genes facilitate the malignant progression of OS and may be employed as prognostic indicators and therapeutic targets in OS.

Treatment and management of medullary thyroid microcarcinoma: a 10-year retrospective study from a single center.

To explore individualized treatment and management methods for medullary thyroid microcarcinoma (MTMC). Clinical data of patients with medullary thyroid carcinoma with a diameter ≤1 cm admitted to the First Affiliated Hospital of Kunming Medical University from June 2013 to June 20× were collected. Combined with different treatment guidelines for medullary thyroid carcinoma, factors affecting lymph node metastasis and postoperative disease status were analyzed. Twenty-nine patients with MTMC were included in the analysis, including 24 patients who underwent total thyroidectomy, 5 who underwent thyroid gland lobectomy, and 13 who experienced postoperative lymph node metastasis. Multifocal tumor and calcitonin (Ctn) were the influencing factors, while multifocal tumor, Ctn, lymph node metastasis, and AJCC stage affected the dynamic risk stratification of postoperative disease. Calcitonin detection is an important method for detecting MTMC. A tumor diameter ≤1 cm does not indicate that the tumor is in the early stage. The presence of multifocal tumors and Ctn should be used as important indicators for preoperative evaluation. Dynamic stratified risk assessment is critical in postoperative follow-up.

A Preoperative Prediction Model for Lymph Node Metastasis in Patients with Gastric Cancer Using a Machine Learning-based Ultrasomics Approach.

This study aimed to develop an ultrasomics model for predicting lymph node metastasis preoperative in patients with gastric cancer (GC). This study enrolled GC patients who underwent preoperative ultrasound examination. Manual segmentation of the region of interest (ROI) was performed by an experienced radiologist to extract radiomics features using the Pyradiomics software. The Z-score algorithm was used for feature normalization, followed by the Wilcoxon test to identify the most informative features. Linear prediction models were constructed using the least absolute shrinkage and selection operator (LASSO). The performance of the ultrasomics model was evaluated using the area under curve (AUC), sensitivity, specificity, and the corresponding 95% confidence intervals (CIs). A total of 464 GC patients (mean age: 60.4 years ±11.3 [SD]; 328 men [70.7%]) were analyzed, of whom 291 had lymph node metastasis. The patients were randomly assigned to either the training (n=324) or test (n=140) sets, using a 7:3 ratio. An ultrasomics model that consisted of 19 radiomics features was developed using Wilcoxon and LASSO algorithms in the training set. Our ultrasomics model showed moderate performance for lymph node metastasis prediction in both the training (AUC: 0.802, 95%CI: 0.752-0.851, P<0.001) and test sets (AUC: 0.802, 95%CI: 0.724-0.879, P<0.001). The calibration curve analysis indicated good agreement between the predicted probabilities of ultrasomics and actual lymph node metastasis status. Our study highlights the potential of a machine learning-based ultrasomics model in predicting lymph node metastasis in GC patients, offering implications for personalized therapy approaches.

SERPINH1 modulates apoptosis by inhibiting P62 ubiquitination degradation to promote bone metastasis of prostate cancer

SERPINH1 modulates apoptosis by inhibiting P62 ubiquitination degradation to promote bone metastasis of prostate cancer

Physiological biodistribution on Ga68-PSMA PET/CT and the factors effecting biodistribution

AimThe study aims to determine the physiological and pathophysiological distribution of the radiopharmaceutical (Ga68-PSMA-617) and investigate whether there are differences in distribution according to the laboratory, histopathological and clinical findings that can affect image evaluation. Also, we aimed to determine cut-off values to distinguish physiological and pathological uptake in prostate, bone, and lymph nodes.Materials and Methods229 prostate cancer patients who underwent Ga68-PSMA PET/CT at our department were retrospectively analyzed. The patients were grouped according to PET/CT results, Gleason scores, PSA values, received treatments, metastatic status and other laboratory values. The SUV values of the organs, tissues, and pathological lesions of the patients in these subgroups were compared among themselves.ResultsNo significant difference was detected in the physiological uptake of lymph nodes and bone between the groups. In the group with patients that received androgen deprivation therapy (ADT), the bone metastasis SUV values were found to be higher and the SUV values of the submandibular gland and renal cortex were found to be lower (Mann–Whitney U, p = 0.043; 0.004; 0.01, respectively). In the group with patients who received radiotherapy, the normal prostate tissue SUV values were determined to be higher (Mann–Whitney U, p = 0.009). The SUV values of the submandibular gland, muscle, liver, and blood pool were found to be lower in the group of patients with high serum LDH values. The cut-off SUVmax value was determined to be 6.945 (sensitivity 89.6%, specificity 98.1%) for primary prostate lesion; 4.72 for lymph node metastasis; 4.25 for bone metastasis. The serum PSA cut-off value to distinguish the negative/positive groups was found to be 1,505 (sensitivity 79.7%, specificity 77.3%).ConclusionIn conclusion, PSMA-617 demonstrates a similar biodistribution with other PSMA ligands. The physiological uptake of lymph nodes and bone which are mostly metastasized in prostate cancer, are not affected by the factors we examined. It should be kept in mind that the normal prostate tissue uptake may increase in patients receiving radiotherapy, and the physiological/pathological uptake of the organs may differ due to the changes in PSMA expression in patients receiving ADT, tumor burden, and kidney function may affect the biodistribution.

Development and validation of a clinical predictive model for high-volume lymph node metastasis of papillary thyroid carcinoma

The central lymph node metastasis (CLNM) status in the cervical region serves as a pivotal determinant for the extent of surgical intervention and prognosis in papillary thyroid carcinoma (PTC). This paper seeks to devise and validate a predictive model based on clinical parameters for the early anticipation of high-volume CLNM (hv-CLNM, > 5 nodes) in high-risk patients. A retrospective analysis of the pathological and clinical data of patients with PTC who underwent surgical treatment at Medical Centers A and B was conducted. The data from Center A was randomly divided into training and validation sets in an 8:2 ratio, with those from Center B serving as the test set. Multifactor logistic regression was harnessed in the training set to select variables and construct a predictive model. The generalization ability of the model was assessed in the validation and test sets. The model was evaluated through the receiver operating characteristic area under the curve (AUC) to predict the efficiency of hv-CLNM. The goodness of fit of the model was examined via the Brier verification technique. The incidence of hv-CLNM in 5897 PTC patients attained 4.8%. The occurrence rates in males and females were 9.4% (128/1365) and 3.4% (156/4532), respectively. Multifactor logistic regression unraveled male gender (OR = 2.17, p < .001), multifocality (OR = 4.06, p < .001), and lesion size (OR = 1.08 per increase of 1 mm, p < .001) as risk factors, while age emerged as a protective factor (OR = 0.95 per an increase of 1 year, p < .001). The model constructed with four predictive variables within the training set exhibited an AUC of 0.847 ([95%CI] 0.815–0.878). In the validation and test sets, the AUCs were 0.831 (0.783–0.879) and 0.845 (0.789–0.901), respectively, with Brier scores of 0.037, 0.041, and 0.056. Subgroup analysis unveiled AUCs for the prediction model in PTC lesion size groups (≤ 10 mm and > 10 mm) as 0.803 (0.757–0.85) and 0.747 (0.709–0.785), age groups (≤ 31 years and > 31 years) as 0.778 (0.720–0.881) and 0.837 (0.806–0.867), multifocal and solitary cases as 0.803 (0.767–0.838) and 0.809 (0.769–0.849), and Hashimoto’s thyroiditis (HT) and non-HT cases as 0.845 (0.793–0.897) and 0.845 (0.819–0.871). Male gender, multifocality, and larger lesion size are risk factors for hv-CLNM in PTC patients, whereas age serves as a protective factor. The clinical predictive model developed in this research facilitates the early identification of high-risk patients for hv-CLNM, thereby assisting physicians in more efficacious risk stratification management for PTC patients.

Prediction of moderate and severe toxicities of chemotherapy in older patients with cancer: a propensity weighted analysis of ELCAPA cohort.

Currently available predictive models for chemotherapy-related toxicity are not sufficiently discriminative in older patients with cancer and do not consider moderate toxicities. The purpose of this study was to identify factors associated with moderate and severe chemotherapy toxicities in older patients with cancer. Patients aged 70+ recruited in the prospective ELCAPA cohort were analyzed. A total of 837 patients with data on toxicities had received chemotherapy without other systemic treatment and were included between 2015 and 2022. To adjust for any imbalances in the distribution of covariates between patients receiving single-agent chemotherapy vs combination chemotherapy, we applied overlap weighting (a propensity-score-based technique). We used multinomial logistic regression. Median (interquartile range) age was 81 (77-84). Forty-one percent experienced moderate toxicity, and 33% experienced severe toxicity. Hematologic toxicities accounted for 53% of severe toxicities and 66% of moderate toxicities. Age <80 years, cancer type, metastatic status, Eastern Cooperative Oncology Group performance status (ECOG-PS) >1, no cognitive impairment were associated with combination chemotherapy decision. In a univariate analysis with overlap weighting, no factors were associated with moderate toxicity. Hemoglobin < 0g/dL and a CIRS-G score >12 were associated with severe toxicity. In a multivariate analysis, only hemoglobin < 10g/dL was independently associated with severe toxicity, adjusted OR 2.96 (95% CI, 1.20-7.29). By addressing indication bias for combination chemotherapy decision, only anemia and not cancer type, combination chemotherapy was predicting for severe chemotherapy-related toxicity in older patients with cancer. We did not find any predictors of moderate chemotherapy-related toxicity.

Elevated expression of ECT2 as a diagnostic marker and prognostic indicator in endometrial cancer

ObjectivesThe study aims to investigate genes associated with endometrial cancer (EC) progression to identify new biomarkers for early detection. MethodsDifferentially expressed genes (DEGs), Series test of cluster (STC) and protein–protein interaction analyses identified hub genes in EC. Clinical samples were utilized to examine the expression pattern of ECT2, assess its prognostic value, and evaluate its diagnostic potential. ResultsUpregulated DEGs were significantly enriched in cancer-related processes and pathways. Validations across databases identified ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5 as potential hub genes, with ECT2 exhibiting the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. Furthermore, ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, and downregulated in the MMRd and NSMP groups, suggesting a moderate prognosis. In clinical samples, ECT2 expression increased from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC, effectively distinguishing between benign and malignant endometria. High ECT2 expression was associated with an unfavourable prognosis. ConclusionsECT2 expression significantly rises in AH and EC, showing high accuracy in distinguishing between benign and malignant endometria. ECT2 emerges as a promising biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.

Predictors of lung cancer subtypes and lymph node status in non-small-cell lung cancer: intravoxel incoherent motion parameters and extracellular volume fraction

ObjectiveTo determine the performance of intravoxel incoherent motion (IVIM) parameters and the extracellular volume fraction (ECV) in distinguishing between different subtypes of lung cancer and predicting lymph node metastasis (LNM) status in patients with non-small-cell lung cancer (NSCLC).MethodsOne hundred sixteen patients with lung cancer were prospectively recruited. IVIM, native, and postcontrast T1 mapping examinations were performed, and the T1 values were measured to calculate the ECV. The differences in IVIM parameters and ECV were compared between NSCLC and small-cell lung cancer (SCLC), adenocarcinoma (Adeno-Ca) and squamous cell carcinoma (SCC), and NSCLC without and with LNM. The assessment of each parameter’s diagnostic performance was based on the area under the receiver operating characteristic curve (AUC).ResultsThe apparent diffusion coefficient (ADC), true diffusion coefficient (D), and ECV values in SCLC were considerably lower compared with NSCLC (all p < 0.001, AUC > 0.887). The D value in SCC was substantially lower compared with Adeno-Ca (p < 0.001, AUC = 0.735). The perfusion fraction (f) and ECV values in LNM patients were markedly higher compared with those without LNM patients (p < 0.01, < 0.001, AUC > 0.708).ConclusionIVIM parameters and ECV can serve as non-invasive biomarkers for assisting in the pathological classification and LNM status assessment of lung cancer patients.Critical relevance statementIVIM parameters and ECV demonstrated remarkable potential in distinguishing pulmonary carcinoma subtypes and predicting LNM status in NSCLC.Key PointsLung cancer is prevalent and differentiating subtype and invasiveness determine the treatment course.True diffusion coefficient and ECV showed promise for subtyping and determining lymph node status.These parameters could serve as non-invasive biomarkers to help determine personalized treatment strategies.Graphical

Differential NEUROD1, ASCL1, and POU2F3 Expression Defines Molecular Subsets of Bladder Small Cell/Neuroendocrine Carcinoma With Prognostic Implications

Small cell carcinomas (SMC) of the lung are now molecularly classified based on the expression of transcriptional regulators (NEUROD1, ASCL1, POU2F3, and YAP1) and DLL3, which has emerged as an investigational therapeutic target. PLCG2 has been shown to identify a distinct subpopulation of lung SMC with stem cell-like and prometastasis features and poor prognosis. We analyzed the expression of these novel neuroendocrine markers and their association with traditional neuroendocrine markers and patient outcomes in a cohort of bladder neuroendocrine carcinoma (NEC) consisting of 103 SMC and 19 large cell NEC (LCNEC) assembled in tissue microarrays. Coexpression patterns were assessed and integrated with detailed clinical annotation including overall (OS) and recurrence-free survival (RFS) and response to neoadjuvant/adjuvant chemotherapy. We identified 5 distinct molecular subtypes in bladder SMC based on the expression of ASCL1, NEUROD1, and POU2F3: ASCL1+/NEUROD1− (n = 33; 34%), ASCL1− /NEUROD1+ (n = 21; 21%), ASCL1+/NEUROD1+ (n = 17; 17%), POU2F3+ (n = 22, 22%), and ASCL1− /NEUROD1− /POU2F3− (n = 5, 5%). POU2F3+ tumors were mutually exclusive with those expressing ASCL1 and NEUROD1 and exhibited lower expression of traditional neuroendocrine markers. PLCG2 expression was noted in 33 tumors (32%) and was highly correlated with POU2F3 expression (P < .001). DLL3 expression was high in both SMC (n = 72, 82%) and LCNEC (n = 11, 85%). YAP1 expression was enriched in nonneuroendocrine components and negatively correlated with all neuroendocrine markers. In patients without metastatic disease who underwent radical cystectomy, PLCG2+ or POU2F3+ tumors had shorter RFS and OS (P < .05), but their expression was not associated with metastasis status or response to neoadjuvant/adjuvant chemotherapy. In conclusion, the NEC of the bladder can be divided into distinct molecular subtypes based on the expression of ASCL1, NEUROD1, and POU2F3. POU2F3-expressing tumors represent an ASCL1/NEUROD1-negative subset of bladder NEC characterized by lower expression of traditional neuroendocrine markers. Marker expression patterns were similar in SMC and LCNEC. Expression of PLCG2 and POU2F3 was associated with shorter RFS and OS. DLL3 was expressed at high levels in both SMC and LCNEC of the bladder, nominating it as a potential therapeutic target.

Stratifying osteosarcoma patients using an epigenetic modification-related prognostic signature: implications for immunotherapy and chemotherapy selection.

Osteosarcoma (OS) poses significant challenges in treatment and lacks reliable prognostic markers. Epigenetic alterations play a crucial role in disease progression. This study aimed to develop an accurate prognostic signature for OS using epigenetic modification genes (EMGs). The Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-OS cohort was analyzed. Univariate Cox analysis identified survival-associated EMGs. Based on least absolute shrinkage and selection operator (LASSO) regression and multivariate analysis, a 6-gene prognostic signature termed the epigenetic modification-related prognostic signature (EMRPS) was derived in the testing cohort. Kaplan-Meier and receiver operating characteristic (ROC) curve analysis confirmed predictive accuracy through internal and external validation (GEO accession GSE21257). A prognostic nomogram incorporating EMRPS and clinical features was constructed. Transcriptomic analysis including differential gene expression, Gene Ontology (GO), gene set enrichment analysis (GSEA), and immune infiltration analysis was conducted to explore mechanisms linking EMRPS to OS prognosis. Additionally, EMRPS impact on drug sensitivity was predicted. A 6-gene EMRPS comprising DDX24, DNAJC1, HDAC4, SIRT7, SP140 and UHRF2 was successfully developed. The high-risk group showed significantly shorter survival, consistently observed in both internal and external validation. EMRPS demonstrated high predictive efficacy for 1-, 3-, and 5-year overall survival, with area under curve (AUC) >0.85 in training and ~0.7 in testing. The nomogram integrating age, gender, metastasis status, and EMRPS exhibited high predictive performance based on concordance index analysis. Mechanistic analysis indicated the low-risk group had increased immune infiltration and activity with higher immune checkpoint expression, reflecting an immune-activated tumor microenvironment (TME) suitable for immunotherapy. Drug sensitivity analysis revealed the low-risk group had increased sensitivity to cisplatin, a first-line OS chemotherapy. Our study successfully established an efficient EMRPS and nomogram, highlighting their potential as novel prognostic markers and indicators for selecting appropriate immunotherapy and chemotherapy candidates in OS treatment.

PP01.14 Healthcare Utilization Amongst Patients with NSCLC Stratified by Metastatic Status Before and After Testing with a Host Immune Classifier (HIC)

PP01.14 Healthcare Utilization Amongst Patients with NSCLC Stratified by Metastatic Status Before and After Testing with a Host Immune Classifier (HIC)

Expression and diagnostic value of serum free light chain in lung cancer.

The expression of serum free light chain (FLC) is abnormal in various diseases, but its role in lung cancer remains unclear. This study aims to investigate the expression and diagnostic value of serum FLC in lung cancer. A total of 80 lung cancer patients treated at Xiangdong Hospital, Hunan Normal University from January to December 2021 were selected as the lung cancer group. Another 80 healthy individuals undergoing routine physical examinations during the same period were chosen as the control group. General information and serum κFLC and λFLC levels were collected for all subjects. Clinical indicators such as serum carcinoembryonic antigen (CEA), cytokeratin fragment antigen 21-1 (CYFRA21-1) levels, tumor diameter, histological type, TNM stage, and lymph node metastasis status were recorded for lung cancer patients. The expression levels of serum FLC [κFLC, λFLC, and FLC (κ+λ)] were compared between the lung cancer group and the control group. Lung cancer patients were grouped based on gender, age, smoking history, tumor diameter, TNM stage, histological type, and lymph node metastasis to compare differences in serum κFLC and λFLC levels. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of serum FLC alone and in combination with other indicators in lung cancer. The expression levels of serum FLC (κ+λ) and κFLC were significantly higher in the lung cancer group than those in the control group (both P<0.001), while there was no significant difference in serum λFLC levels between the 2 groups (P>0.05). There were no significant differences in serum κFLC levels among lung cancer patients with different tumor diameters, histological types, or TNM stages (all P>0.05); however, serum κFLC levels were higher in lung cancer patients with lymph node metastasis than in those without, with statistical significance (P=0.033). There were no significant differences in serum λFLC levels based on tumor diameter or histological type (both P>0.05), but serum λFLC levels were higher in stage III+IV and lymph node metastatic lung cancer patients compared to stage I+II and non-metastatic patients, with statistical significance (P=0.033 and P=0.019, respectively). The area under the curve (AUC) for κFLC and CEA in diagnosing lung cancer showed no significant difference (P=0.333). The combination of κFLC+CYFRA21-1 had the highest diagnostic efficacy (AUC=0.875) and sensitivity (71.3%). The AUC for the combined diagnosis of κFLC+λFLC+CEA+CYFRA21-1 was 0.915 (95% CI 0.860 to 0.953, P<0.001). Serum FLC is highly expressed in lung cancer and is associated with its invasion and metastasis. Serum FLC, particularly κFLC, has diagnostic value for lung cancer, and the combined detection of FLC, CEA, and CYFRA21-1 offers the best diagnostic efficacy.

Analysis of lymph node metastasis and survival prognosis in early gastric cancer patients: A retrospective study.

Early gastric cancer (EGC) is a common malignant tumor of the digestive system, and its lymph node metastasis and survival prognosis have been concerning. By retrospectively analyzing the clinical data of EGC patients, we can better understand the status of lymph node metastasis and its impact on survival and prognosis. To evaluate the prognosis of EGC patients and the factors that affect lymph node metastasis. The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study. There were 561 males and 450 females. The mean age was 58 ± 11 years. The patient underwent radical gastrectomy. The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens. The outcomes were as follows: (1) Lymph node metastasis in EGC patients; (2) Analysis of influencing factors of lymph node metastasis in EGC; and (3) Analysis of prognostic factors in patients with EGC. Normally distributed measurement data are expressed as mean ± SD, and a t test was used for comparisons between groups. The data are expressed as absolute numbers or percentages, and the chi-square test was used for comparisons between groups. Rank data were compared using a nonparametric rank sum test. A log-rank test and a logistic regression model were used for univariate analysis. A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis. The Kaplan-Meier method was used to calculate the survival rate and construct survival curves. A log-rank test was used for survival analysis. Analysis of influencing factors of lymph node metastasis in EGC. The results of the multifactor analysis showed that tumor length and diameter, tumor site, tumor invasion depth, vascular thrombus, and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC (odds ratios = 1.80, 1.49, 2.65, 5.76, and 0.60; 95%CI: 1.29-2.50, 1.11-2.00, 1.81-3.88, 3.87-8.59, and 0.48-0.76, respectively; P < 0.05). Analysis of prognostic factors in patients with EGC. All 1011 patients with EGC were followed up for 43 (0-13) months. The 3-year overall survival rate was 97.32%. Multivariate analysis revealed that age > 60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC (hazard ratio = 9.50, 2.20; 95%CI: 3.31-27.29, 1.00-4.87; P < 0.05). Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged > 60 years and ≤ 60 years were 99.37% and 94.66%, respectively, and the difference was statistically significant (P < 0.05). The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42% and 97.92%, respectively, and the difference was statistically significant (P < 0.05). The lymph node metastasis rate of EGC patients was 23.64%. Tumor length, tumor site, tumor infiltration depth, vascular cancer thrombin, and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients. Age > 60 years and lymph node metastasis are independent risk factors for EGC prognosis.

The role of intraoperative central lymph node biopsy in the treatment of clinically low-risk PTMC.

To evaluate the role of intraoperative frozen biopsy of central lymph nodes in central neck dissection and thyroidectomy in patients of unilateral, clinically negative nodes (cN0) papillary thyroid microcarcinoma (PTMC) without extra-glandular invasion. The clinical data of 465 patients were collected retrospectively. Part of prelaryngeal, pretracheal and ipsilateral paratracheal lymph nodes were taken for frozen pathological examination during the operation. Then the thyroid lobe on the tumor side and isthmus were excised, and central neck dissection of the affected side was performed in all patients. The number of metastases in entire central lymph nodes of the affected side can be obtained by postoperative paraffin pathology. If the number of positive lymph nodes during surgery is ≥3, contralateral gland resection was performed. In this group of 465 patients, there were 186 cases with central lymph node metastasis. The Kappa coefficient of consistency between frozen pathology and paraffin pathology in central lymph nodes was 0.605. The ROC curve for the number of intraoperative frozen metastases-postoperative pathological metastases over 5 showed that the AUC of the curve was 0.793, while the maximum Youden index was 0.5259, whose corresponding number of positive lymph nodes was 3. Intraoperative central lymph nodes biopsy can be used as an important indicator for the status of central lymph node metastasis in unilateral cN0 PTMC patients without extra-glandular invasion and a determinant for central lymph node dissection. While the number of positive lymph nodes intraoperatively is ≥3, total thyroidectomy should be considered.

Patients with stage IV colorectal carcinoma selected for palliative primary tumor resection and systemic therapy survive longer compared with systemic therapy alone - A retrospective comparative cohort study.

To compare the survival of palliative stage IV colorectal cancer patients selected for primary tumor resection and systemic treatment (PTR+SYST) to patients with systemic treatment only (SYST). About 20-25% of all colorectal cancer patients are diagnosed with stage IV disease. The benefit of primary tumor resection in the palliative situation is therefore of high concern. However, empirical evidence from randomized and observational studies is inconsistent. Mortality after PTR and systemic treatment was compared to systemic treatment alone in a retrospective observational cohort of patients diagnosed 2012-2020 from the cancer registry in the federal state of Brandenburg (Germany), excluding patients with rectal cancer of the lower two-thirds, emergency procedures, unknown ECOG status, ECOG >2, unknown metastatic status or unclear grading. Of 480 patients, 416 died during an average follow-up of 23 months in mean. 12-months survival was 75% after PTR+SYST compared with 49% after SYST (HR=0.39, 95% CI 0.29-0.53, P<0.001). The difference persisted to 36 months (28% vs. 13%, HR=0.53, 95% CI 0.43-0.66, P<0.001). Results were similar after multivariate adjustment, propensity score matching and delayed entry. Patients with stage IV colorectal carcinoma who are selected for primary tumor resection in combination with systemic therapy and who receive such treatment survive longer compared with patients who receive only systemic treatment. Whether the difference is due to selection of patients or PTR remains unclear. At present, current practice of selecting patients for PTR appears to do no harm.

Both intra- and peri-tumoral radiomics signatures can be used to predict lymphatic vascular space invasion and lymphatic metastasis positive status from endometrial cancer MR imaging.

To identify lymphatic vascular space invasion (LVSI) and lymphatic node metastasis (LNM) status of endometrial cancer (EC) patients, using radiomics based on MRI images. Five hundred and ninety-eight EC patients between January 2015 and September 2020 from two institutions were retrospectively included. Tumoral regions on DWI, T1CE, and T2W images were manually outlined. Radiomics features were extracted from tumor region and peri-tumor region of different thicknesses. We established sub-models to select features from each smaller category. Using this method, we separately constructed radiomic signatures for intra-tumoral and peri-tumoral images using different sequences. We constructed intra-tumoral and peri-tumoral models by combining their features, and a multi-sequence model by combining logits. Models weretrained with 397 patients and validated with 170 internal and 31 external patients. For LVSI positive/LNM positive status identification, the multi-parameter MRI radiomics model achieved the area under curve (AUC) values of 0.771 (95%CI: [0.692-0.849])/0.801 (95%CI: [0.704, 0.898]) and 0.864 (95%CI: [0.728-1.000])/0.976 (95%CI: [0.919, 1.000]) in internal and external test cohorts, respectively. Intra-tumoral and peri-tumoral radiomics signatures based on mpMRI can both be used to identify LVSI or LNM status in EC patients non-invasively. Further studies on LVSI and LNM should pay attention to both of them.

Effect of microRNA-141-3p, E2F3, CDK3, and KAT2B overexpression on histologic tumor grade and metastasis status in untreated breast cancer tissues

Introduction: Increasing evidence has reported gene expression alterations in breast cancer (BC) tissues, necessitating their investigating to highlight the molecular basis of the disease development or progression. This study investigated the expression of miR-141, E2F3, CDK3, TP53, and KAT2B, and their association with histologic grade and metastasis in BC tissues. Methods: The RNA expression level of miR-141, E2F3, CDK3, TP53, and KAT2B genes was analyzed in 23 BC and 23 normal tissue samples by RT-qPCR. The associations of the expression level of these genes with clinicopathological features of the BC tissue samples were evaluated. The study also explored the correlation between RNA levels of genes and miR-141. Results: Expression of miR-141, E2F3, CDK3, and KAT2B demonstrated significantly higher levels in BC tumor than normal tissues. TP53 expression showed an increase in tumor compared to normal tissues, although it was insignificant. Moreover, increased RNA expression of miR-141, E2F3, CDK3, and KAT2B corresponded to the advanced stage and regional metastasis of BC. Additionally, the results demonstrated a significant correlation between RNA expression levels of miR-141 with CDK3 and E2F3 with KAT2B. Conclusion: Our findings highlighted clinicopathologic indicators that were relevant to aggressive BC. Besides, Correlations between overexpression of miR-141, E2F3, CDK3, and KAT2B in BC tissues suggest regulatory effects. Taken together, it seems results of this study could provide evidence that dysregulation of gene expression contributes significantly to unveiling the underlying molecular basis of BC.

MDB-14. TREATMENT AND OUTCOMES OF MEDULLOBLASTOMA: FIRST REPORT FROM ARMENIA

Abstract BACKGROUND Medulloblastoma accounts for approximately 20% of all primary CNS tumors. Although advanced diagnostic tools and risk-adjusted treatment regimens produce a more than 70% five-year overall survival in HICs the data from LMICs is scarce. This study analyzed the outcome of children with medulloblastoma treated in Armenia. METHODS Demographic and treatment data was collected from medical records of pediatric and young adult patients (≤ 25 years) treated in four major centers in Armenia from 1995-2023. Event-free survival and overall survival were estimated using Kaplan-Meier method. RESULTS During the study period 41 patients with medulloblastoma were registered (20.7% of primary CNS tumors), male-to-female ratio 1.73:1. The median age at diagnosis was 8 years (range: 0.83-25 years). Most common presenting symptoms were nausea and vomiting (82.5%), headache (75%) and ataxia (50%). Metastatic status was evaluated (spinal MRI and CSF cytology) in 48.8% of patients (25% M+ disease). Risk assessment was available for 30 patients (12 standard-risk and 18 high-risk). All patients underwent surgery, gross-total or near-total resection was achieved in 53.7% of cases. Radiation therapy and chemotherapy given to 63.4% and 58.5% of cases, respectively. Of 8 infants included in this study 4 were treated with chemotherapy only, 3 died without further treatment. Median time from surgery to RT/chemotherapy was 6 weeks. Five-year EFS and OS were estimated 58.3% (95% CI 37.5-71%) and 62.5% (95% CI 43.75-77.1%), respectively. Patients with GTR/NTR had a higher OS than patients with STR (83.3% vs 33.3%, p=0.005). No statistically significant difference in EFS/OS was detected based on risk group, metastatic status, or completion of the protocol. CONCLUSIONS OS was lower than expected in this study. Accurate risk assessment and risk-stratified treatment were often lacking during the study period. Compliance to the standardized treatment protocols and multidisciplinary care are needed for improving outcomes of medulloblastoma.