Lymph Node Metastasis Research Articles

Synergizing traditional CT imaging with radiomics: a novel model for preoperative diagnosis of gastric neuroendocrine and mixed adenoneuroendocrine carcinoma.

To develop diagnostic models for differentiating gastric neuroendocrine carcinoma (g-NEC) and gastric mixed adeno-neuroendocrine carcinoma (g-MANEC) from gastric adenocarcinoma (g-ADC) based on traditional contrast enhanced CT imaging features and radiomics features. We retrospectively analyzed 90 g-(MA)NEC (g-MANEC and g-NEC) patients matched 1:1 by T-stage with 90 g-ADC patients. Traditional CT features were analyzed using univariable and multivariable logistic regression. Tumor segmentation and radiomics features extraction were performed with Slicer and PyRadiomics. Feature selection was conducted through univariable analysis, correlation analysis, LASSO, and multivariable stepwise logistic. The combined model incorporated clinical and radiomics predictors. Diagnostic performance was assessed with ROC curves and DeLong's test. The models' diagnostic efficacy was further validated in subgroup of g-NEC vs. g-ADC and g-MANEC vs. g-ADC cases. Tumor necrosis and lymph node metastasis were independent predictors for differentiating g-(MA)NEC from g-ADC (P < 0.05). The clinical model's AUC was 0.700 (training) and 0.667(validation). Five radiomics features were retained, with the radiomics model showing AUC of 0.809 (training) and 0.802 (validation). The combined model's AUCs were 0.853 (training) and 0.812 (validation), significantly outperforming the clinical model (P < 0.05). Subgroup analysis revealed that the combined model exhibited acceptable performance in differentiating g-NEC from g-ADC and g-MANEC from g-ADC, with AUCof0.887 and 0.823 in the training cohort and 0.852 and 0.762 in the validation cohort. A combined model based on traditional CT imaging and radiomic features provides a non-invasive and effective preoperative diagnostic method for differentiating g-(MA)NEC from g-ADC.

Nomogram predicts cervical lymph node metastasis of pathological subtypes of papillary thyroid carcinoma.

Pathological subtypes of papillary thyroid carcinoma (PTC) are important factors in thyroid cancer. Some rare subtypes exhibit extensive lymph node metastasis. These pathological subtypes should receive more attention in clinical practice. Patients with different pathological subtypes of PTC were selected from the SEER database. Logistic regression, random forest, and bootstrap aggregating (bagging) methods were employed to screen for risk factors associated with cervical lymph node metastasis in the training cohort. A nomogram was established based on the model with the largest area under the curve (AUC) and evaluated using calibration curves. Decision curve analysis (DCA) was used to evaluate the clinical benefit to patients. The nomogram was validated in depth by 200 iterations of tenfold cross-validation. A total of 7,882 patients were included in the analysis, with 5,516 patients in the training group and 2,366 patients in the testing group. The logistic regression model achieved the highest AUC of 0.7396. Sex, age, race, extension (extrathyroidal extension), pathological type, and primary tumour size were identified as independent risk factors for cervical lymph node metastasis (p < 0.05). The calibration curve indicated that the model was well calibrated. DCA indicated that the nomogram model had good clinical practicability. In clinical practice, it is important to consider the pathological subtypes of PTC. The established nomogram can serve as a predictive tool for assessing cervical lymph node metastasis.

Association of Radioactive Iodine Administration With Outcome Among Patients With Low-Risk Differentiated Thyroid Cancer: A Real-World Data Analysis.

Despite the generally favourable long-term prognosis of low-risk differentiated thyroid cancer (DTC), questions remain about disease-free survival (DFS) after initial treatment, particularly regarding the use of radioactive iodine (RAI). Although there are RCT trial confirming that RAI ablation therapy is not superior to follow-up in terms of the 3-year DFS rate in low-risk thyroid cancer, its longer-term prognosis remains to be established. The objective of this study was to assess the impact of RAI ablation on the presence of structural persistent/recurrent disease in patients with low-risk DTC. We retrospectively identified 720 low-risk DTC patients who had undergone total or near-total thyroidectomy (TT) at a tertiary medical centre between January 2008 and July 2018. Propensity scores were calculated using a multivariable logistic regression model that accounted for age, sex, tumour size, neck dissection, multifocality, capsular invasion and lymph node (LN) metastasis. We compared DFS between patients who received RAI and those who did not using log-rank tests and multivariate Cox analyses. Subgroup analyses were also conducted. Of the total cohort, 180 (25.0%) patients received RAI, while 540 (75.0%) did not before matching. The median follow-up duration was 59.5 months. After matching, the RAI group comprised 135 (39.8%) patients and the non-RAI group comprised 204 (60.2%) patients. In the entire cohort, the 5-year DFS rate was 97.6% for patients receiving RAI compared to 96.8% for those not receiving RAI (p = 0.704). In the matched cohort, the rates were 98.5% and 95.6%, respectively (p = 0.090). Matched multivariate Cox analysis demonstrated that RAI was neither significantly nor independently associated with DFS (hazard ratio [HR] = 0.29; 95% CI 0.06-1.37; p = 0.118). Further subgroup analyses reaffirmed that RAI ablation did not significantly reduce the risk of developing structural persistent/recurrent disease. Administering RAI ablation following TT did not result in improved DFS for low-risk DTC patients. Our findings suggest that decisions regarding RAI should be made judiciously to avoid overtreatment in this clinical scenario.

Roles of miR-20a-5p in breast cancer based on the clinical and multi-omic (CAMO) cohort and in vitro studies

MicroRNAs are involved in breast cancer development and progression, holding potential as biomarkers and therapeutic targets or tools. The roles of miR-20a-5p, a member of the oncogenic miR-17-92 cluster, remain poorly understood in the context of breast cancer. In this study, we elucidate the role of miR-20a-5p in breast cancer by examining its associations with breast cancer risk factors and clinicopathological features, and its functional roles in vitro. Tissue microarrays from 313 CAMO cohort breast cancer surgical specimens were constructed, in situ hybridization was performed and miR-20a-5p expression was semiquantitatively scored in tumor stromal fibroblasts, and in the cytoplasm and nuclei of cancer cells. In vitro analysis of the effect of miR-20a-5p transfection on proliferation, migration and invasion was performed in three breast cancer cell lines. High stromal miR-20a-5p was associated with higher Ki67 expression, and higher odds of relapse, compared to low expression. Compared to postmenopausal women, women who were premenopausal at diagnosis had higher odds of high stromal and cytoplasmic miR-20a-5p expression. Cytoplasmic miR-20a-5p was significantly associated with tumor grade. In tumors with high cytoplasmic miR-20a-5p expression compared to low expression, there was a tendency towards having a basal-like subtype and high Ki67. In contrast, high nuclear miR-20a-5p in cancer cells was associated with smaller tumor size and lower odds of lymph node metastasis, compared to low nuclear expression. Transfection with miR-20a-5p in breast cancer cell lines led to increased migration and invasion in vitro. While the majority of our results point towards an oncogenic role, some of our findings indicate that the associations of miR-20a-5p with breast cancer related risk factors and outcomes may vary based on tissue- and subcellular location. Larger studies are needed to validate our findings and further investigate the clinical utility of miR-20a-5p.

Machine learning predictive models and risk factors for lymph node metastasis in non-small cell lung cancer

BackgroundThe prognosis of non-small cell lung cancer (NSCLC) is substantially affected by lymph node metastasis (LNM), but there are no noninvasive, inexpensive methods of relatively high accuracy available to predict LNM in NSCLC patients.MethodsClinical data on NSCLC patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for LNM were recognized LASSO and multivariate logistic regression. Six predictive models were constructed with machine learning based on risk factors. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of the model. Subgroup analysis with different T-stages was performed on an optimal model. A webpage LNM risk calculator for optimal model was built using the Shinyapps.io platform.ResultsWe enrolled 64,012 NSCLC patients, of whom 26,611 (41.57%) had LNM. Using multivariate logistic regression, we finally identified 10 independent risk factors for LNM: age, sex, race, histology, primary site, grade, T stage, M stage, tumor size, and bone metastases. GLM is the optimal model among all six machine learning models in both the training and validation cohorts. Subgroup analyses revealed that GLM has good predictability for populations with different T staging. A webpage LNM risk calculator based on GLM was posted on the shinyapps.io platform (https://wubopredict.shinyapps.io/dynnomapp/).ConclusionThe predictive model based on GLM can be used to precisely predict the probability of LNM in NSCLC patients, which was proven effective in all subgroup analyses according to T staging.

Meta-analysis of prediction models for predicting lymph node metastasis in thyroid cancer

BackgroundThe purpose of this systematic review and meta-analysis is to assess the efficacy of various machine learning (ML) techniques in predicting preoperative lymph node metastasis (LNM) in patients diagnosed with papillary thyroid carcinoma (PTC). Although prior studies have investigated the potential of ML in this context, the current evidence is not sufficiently strong. Hence, we undertook a thorough analysis to ascertain the predictive accuracy of different ML models and their practical relevance in predicting preoperative LNM in PTC patients.Materials and methodsIn our search, we thoroughly examined PubMed, Cochrane Library, Embase, and Web of Science, encompassing their complete database history until December 3rd, 2022. To evaluate the potential bias in the machine learning models documented in the included studies, we employed the Prediction Model Risk of Bias Assessment Tool (PROBAST).ResultsA total of 107 studies, involving 136,245 patients, were included. Among them, 21,231 patients showed central LNM (CLNM) and 4,637 had lateral LNM (LLNM). The meta-analysis results revealed that the c-index for predicting LNM, CLNM, and LLNM were 0.762 (95% CI: 0.747–0.777), 0.762 (95% CI: 0.747–0.777), and 0.803 (95% CI: 0.773–0.834) in the training set, and 0.773 (95% CI: 0.754–0.791), 0.762 (95% CI: 0.747–0.777), and 0.829 (95% CI: 0.779–0.879) in the validation set, respectively. A total of 134 machine learning-based prediction models were included, covering 10 different types. Logistic Regression (LR) was the most commonly used model, accounting for 81.34% (109/134) of the included models.ConclusionsMachine learning methods have shown a certain level of accuracy in predicting preoperative LNM in PTC patients, indicating their potential as a predictive tool. Their use in the clinical management of PTC holds great promise. Among the various ML models investigated, the performance of logistic regression-based nomograms was deemed satisfactory.

MiR-559 rs58450758 polymorphism is associated with colorectal cancer risk and prognosis in Chinese Han population.

Aim: This research examined the correlation between miR-559 rs58450758 and the clinical pathological characteristics and prognosis of CRC.Materials & methods: RT-qPCR was utilized to assess the miR-559 expression levels. Chi-square test was used to investigate the relationship between miR-559 and clinical features. The association between rs58450758 different genotypes and CRC risk, as well as clinical pathological parameters, was explored, utilizing logistic regression analysis and chi-square tests. The Cox regression model and Kaplan-Meier analysis evaluated overall survival in individuals with CRC.Results: The miR-559 was down-regulated in CRC patients' serum. The expressions of miR-559 were significantly associated with tumor size, differentiation, TNM stage and lymph node metastasis. The rs58450758 TT genotype and T allele carriers were more prevalent among CRC patients. The rs58450758 polymorphism was notably linked to tumor size, differentiation, TNM stage and lymph node metastasis in CRC patients. Furthermore, CC genotype carriers exhibited a longer survival period than CT/TT genotypes within the CRC population.Conclusion: The miR-559 rs58450758 polymorphism exhibits promise as a potential biomarker for prognosticating the outcomes of CRC.

The clinical outcome, pathologic spectrum, and genomic landscape for 454 cases of salivary mucoepidermoid carcinoma

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary tumor. A complete understanding of the high heterogeneity of MEC in histology and genetics would help in accurate diagnosis and treatment. Therefore, We evaluated the clinical features, treatment outcomes, and pathological parameters of 454 MECs and analyzed their genomic features using whole-exome sequencing and whole-transcriptome sequencing. We found that MECs predominantly occurred in females and those in their 4th–5th decades. The parotid gland was the most frequently affected site. All patients underwent complete mass resection with lobectomy; 414 patients were alive without relapse at follow-up, after an average period of 62 months (1–116 months). The disease progressed after initial treatment in 40 patients. The lungs were the most common site of distant metastasis. For classical MECs, histologic gradings of the AFIP, modified Healey, and MSK systems were significantly associated with recurrence and lymph nodal metastasis; these gradings were significantly related to lymph nodal metastasis for the subtypes. Older age, minor salivary gland involvement, clinical symptoms, high TNM stage, high-grade tumor, and improper surgical modality were the main prognostic factors. BAP1 was the most frequently mutated gene in MEC. Mutations in CDKN2A, MET, and TP53 were more frequently found in aggressive tumor phenotypes. MAML2 rearrangement was observed in 42% of patients, and EWSR1 rearrangement in 8%. Specific genetic events (in TP53 and FBXW7) with CRTC1::MAML2 fusion superimposed might be associated with unfavorable prognosis. This study provides new insights into precision therapeutic strategies for MEC.

Locoregional event or dyssynchronous distant metastasis: clinicopathological and molecular analysis of contralateral axillary lymph node metastasis in breast cancer patients.

Contralateral axillary lymph node metastasis (CAM) is a rare clinical condition in patients with breast cancer (BC). CAM can be either a locoregional event or a distant metastasis. Molecular application for clonal evolution in BC has not been reported in CAM cases. We studied six patients with CAM with clinical, pathological and/or molecular evidence of distant metastasis; those patients had poor outcomes. Two cases with molecular analysis of paired primary and CAM established clonal evolution of the CAM with its corresponding primary with additional molecular alteration, increased tumour mutation burden, and copy number variations (CNVs) in the CAMs. Four cases containing alterations from genes potentially modulate chromatin organization, supporting chromatin and subsequent transcriptional signature changes are essential in CAM. Molecular analysis is critical to establish the connection between CAM and its primary counterpart. Distant CAM shows clonal evolution compared with its corresponding primary with additional molecular alterations, increased mutation burden and/or copy number variations. CAM should be evaluated individually and handled in a personalized fashion. Evidence of a true metastatic CAM can be supported by distant metastasis to other organs, specific morphological features and/or clonal evolution.

Advances in radiomics applications for intrahepatic cholangiocarcinoma: a comprehensive review and future directions

Radiomics was first introduced by Lambin et al. in 2012, and since then, research in this field has grown rapidly. Researchers have shown great interest in developing efficient methods for automatically extracting a large number of quantitative features from medical images, aiming to enhance diagnostic accuracy and predictive capability. Although there has been a rise in Radiomics studies focusing on intrahepatic cholangiocarcinoma (ICC) in recent years, comprehensive reviews are still relatively scarce. This study explores how Radiomics technology can be utilized in modeling analyses to predict lymph node metastasis, microvascular invasion, and early recurrence of ICC, as well as the application of deep learning in these analyses. This paper provides a brief overview of the current state of Radiomics research and offers references for future studies.

Analysis of Clinicopathological and Molecular Features of Microcystic, Elongated, and Fragmented Pattern Invasion in Endometrioid Endometrial Cancer.

Background: Microcystic, elongated, and fragmented (MELF) invasion is a special invasion pattern in endometrioid endometrial cancer (EEC). This study aimed to investigate the clinical, pathological, and molecular features of the MELF pattern and its prognostic value in patients with EEC. Materials and Methods: The clinical and pathological data of 342 patients with EEC were retrospectively collected at Peking University People's Hospital from January 2019 to December 2022. Some key clinicopathological features were evaluated, including the tumor grade, Federation of Gynecology and Obstetrics (FIGO) staging, cervical stromal involvement, lymph node status, and lymphatic vascular space infiltration (LVSI). Immunohistochemical staining and molecular tests were performed, and the relevant literature was reviewed. Results: The MELF pattern was more prevalent in low-grade EEC. A significant correlation was found between the MELF pattern and advanced FIGO staging, LVSI, the depth of myometrial invasion, cervical stromal involvement, and lymph node metastasis (LNM). The incidence of mismatch-repair-deficient (MMRd) proteins was much higher in the MELF group than in the no-MELF group. Molecular testing revealed that, after copy number-low (CNL), microsatellite instability-high (MSI-H) was the second-most frequent subtype in the MELF group. The recurrence risk did not significantly differ between the MELF and no-MELF groups, but the differences among the four molecular subtypes were statistically significant. However, the MELF group experienced a shorter recurrence time. Among the four molecular subtypes, the recurrence risk was the highest in the CNH subgroup, followed by the MSI-H subgroup. Conclusions: MELF is a special invasion pattern in EEC and is associated with distinct clinicopathological and molecular characteristics, including the latest 2023 FIGO staging. Further research is warranted to explore its implications for treatment strategies and patient outcomes.

Coagulation-related genes for thyroid cancer prognosis, immune infltration, staging, and drug sensitivity.

Thyroid cancer (THCA) is the most common endocrine tumor. Coagulation may be associated with the development of cancer, but its role in THCA patients is not yet clear. In this study, we determined the predictive value of coagulation biomarker D-dimer for THCA patient lateral lymph node metastasis (LLNM) through receiver operating characteristics (ROC) analysis and logistic regression analysis. Subsequently, this study used the TCGA database to identify coagulation-related molecular subtypes through consensus clustering analysis and compared their prognosis. We identified coagulation-related genes (CRGs) associated with prognosis in thyroid cancer through gene expression data and clinical information, and constructed a prognostic model by selecting the prognostic CRGs using LASSO regression. Patients were divided into high-risk and low-risk groups based on the median score. Subsequently, prognosis, clinical characteristics, gene mutation occurrence, immune infiltration, function, and drug sensitivity of the two groups were analyzed. We also constructed a nomogram combining the model and clinical features. Finally, the expression of the prognostic CRGs was validated by RT-qPCR. D-dimers had better performance in predicting LLNM(the area under the curve was 0.656 (95% CI 0.580-0.733), with a cut-off value of 0.065 mg/l), and D-dimer>0.065mg/l was an independent predictor of LLNM. Then, we selected 8 prognostic CRGs to construct a predictive model. The prognosis of low-risk group patients was significantly better than that of high-risk group (P<0.001). The results showed significant differences in clinical characteristics, gene mutation occurrence, immune infiltration, function, and drug sensitivity between the high-risk and low-risk groups. We validated by qPCR that these 8 prognostic CRGs were overexpressed in THCA cell lines. Overall, this study provided an in-depth exploration of the potential role of the coagulation in thyroid cancer and its clinical significance, offering a new theoretical basis and research direction for personalized therapy and prognostic evaluation.

A real-world retrospective study to assess efficacy and safety of alectinib as adjuvant therapy in IB-IIIB NSCLC patients harboring ALK rearrangement.

Alectinib has demonstrated promising disease-free survival (DFS) benefit for early-stage non-small cell lung cancer (NSCLC) patients with ALK rearrangement positive in phase 3 ALINA trial. However, real-world evidence for the efficacy and safety of alectinib in early-stage ALK-positive NSCLC is limited. We retrospectively reviewed 68 patients with stage IB-IIIB ALK-positive NSCLC who underwent complete pulmonary resections from April 2010 to July 2023 at a single institution. 38 (55.9%) enrolled patients had N2 lymph node metastasis, and 17 (24.9%) patients had multi-station N2 metastasis. Patients were stratified into two groups according to the adjuvant treatment regimen, with 19 patients in the alectinib group and 49 patients in the chemotherapy group. There were no significant differences in clinicopathological characteristics between the two groups. After curative resection surgery, patients in alectinib group received oral alectinib at a dose of 600 mg twice daily and patients in chemotherapy group received platinum-based doublet chemotherapy regimen every 3 weeks for 4 cycles. The primary endpoint was 3-year DFS. The Kaplan-Meier method was used to estimate DFS and overall survival (OS). Safety analyses were conducted by comparing the incidence of adverse events between the two groups. At the last follow-up date (January 22th, 2024), A total of 1 (5.3%) and 28 (57.1%) DFS events were observed in alectinib group and chemotherapy group respectively. The 3-year DFS showed significant improvement in the alectinib group compared with chemotherapy group (91.7% vs 60.7%, P=0.051). In the IIIAN2 subgroup, the 3-year DFS rate in the alectinib group reached a satisfactory 87.5%. In both groups, the majority of AEs were graded as level 1 or 2, No grade 3-4 AEs were observed in alectinib group. Alectinib, as adjuvant therapy, demonstrated favorable efficacy and manageable safety in patients with completely resected ALK-positive stage I B-IIIB non-small cell lung cancer. A limitation of this study is the small sample size, and a larger-scale real-world sample study is needed to further evaluate the efficacy and safety of alectinib as adjuvant therapy.

Reduction of Blood Oxidative Stress Following Colorectal Cancer Resection

Background: Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a primary source of oxidative stress, would reduce blood levels of reactive oxygen metabolite derivatives (d-ROMs), a marker of oxidative stress, and biologic antioxidant potential (BAP) levels, a marker of antioxidant potential. Methods: This study included 123 patients who underwent radical resection for colorectal cancer. d-ROM and BAP levels were measured before and one month after surgery. Results: The clinicopathological analysis showed a correlation between preoperative d-ROM levels and tumor size (p &lt; 0.001). This study confirmed a significant reduction in d-ROM levels following tumor resection, indicating reduced systemic oxidative stress. The reduction was significant in stages II and III, but not in stage I. The d-ROM ratio before and after tumor resection was significantly higher in cases with positive lymph node metastasis and larger tumor size. BAP levels showed no significant changes post-surgery. Conclusions: These results suggest that d-ROMs could serve as a valuable biomarker for monitoring tumor burden and surgical efficacy in patients with colorectal cancer.

Prognostic Significance of Combining Cytokeratin-19, E-Cadherin and Ki-67 Analysis in Triple-Negative Breast Cancer with Basal-Like and Non-Basal-Like Phenotype

Triple-negative breast cancer (TNBC) is known to have the worst outcome compared to the other forms of breast cancer. Moreover, molecular markers identified basal-like breast cancer (BLBC) phenotypes to be also related to a worse prognosis. In this study, we evaluated by immunohistochemistry (IHC) the prognostic significance of combining Cytokeratin-19 (CK19), E-cadherin, and Ki-67 tissue expression in triple-negative breast cancer (TNBC) cases presenting a basal-like (BLBC) or a non-basal-like (n-BLBC) phenotype to improve the selection and the monitoring of BC patients with a more aggressive outcome. Herein, when compared to n-BLBC, patients with BLBC showed a positive correlation with lymph node metastasis occurrence and lower survival rates. Immunohistochemistry analysis revealed significantly lower E-cadherin prevalence and higher prevalence of both CK19 and Ki-67 in BLBC when compared to n-BLBC. Spearman correlation showed that E-cadherin is negatively and significantly correlated to CK19 and Ki-67 expressions. Moreover, in BLBC, expressing both CK19 and Ki-67 combined with E-cadherin loss was associated with the worst relapse-free and overall survival. In conclusion, TNBC/BLBC phenotypes simultaneously losing E-cadherin and overexpressing CK19 and Ki-67 markers are the most aggressive forms. This combined analysis could be a predictive marker of poor prognosis.

The value of postoperative contrast-enhanced ultrasound parameters in lymph node metastasis, tumor node metastasis, and treatment response evaluation of resected hepatocellular carcinoma.

To explore the application value of postoperative contrast-enhanced ultrasound (CEUS) parameters for lymph node metastasis (LNM), tumor, node, metastasis staging, and treatment response evaluation of resected hepatocellular carcinoma (HCC). We retrospectively analyzed 100 patients with liver cancer who underwent liver CEUS at our hospital between October 2020 and October 2022. The patient's LNM, pathological staging, and therapeutic effects were recorded based on the histopathological results. CEUS parameters were analyzed and compared CEUS parameters between different lymph node metastases, pathological stages, and therapeutic effects. Twenty-three patients experienced LNM, 77 patients did not experience LNM; and the rise time (RT), peak intensity (PI), and area under the curve (AUC) of the metastatic group were significantly smaller than those of the nonmetastatic group (P < .05). 44 cases were classified into groups I to II by pathological staging, and 56 cases were classified into groups III to IV. The RT, PI, and AUC of groups III to IV were significantly lower than those of groups I-II (P < .05). Seventy-nine cases were complete necrosis, 21 cases were residual or recurrent; The RT, PI, and AUC of the residual or recurrent group were significantly lower than those of the complete necrosis group (P < .05). The receiver operating characteristic curve shows that RT, PI, and AUC have a certain value in evaluating LNM, pathological staging, and treatment response of HCC, and the combined evaluation/evaluation value of these 3 factors is relatively high. The postoperative CEUS parameters RT, PI, and AUC can be used for LNM, pathological staging evaluation, and treatment response evaluation of HCC. Moreover, the combination of the 3 parameters is feasible and valuable in evaluating LNM, tumor, node, metastasis staging, and treatment response of HCC.

Loss of vimentin expression in preoperative biopsies independently predicts poor prognosis, lymph node metastasis and recurrence in endometrial cancer

BackgroundPrecise preoperative risk classification of endometrial cancer is crucial for treatment decisions. Existing clinical markers often fail to accurately predict lymph node metastasis and recurrence risk. Loss of vimentin expression has emerged as a potential marker for predicting recurrence in low-risk endometrial cancer patients. We assessed whether vimentin expression in preoperative biopsies predicts poor prognosis and lymph node metastasis in a large multicentre cohort.MethodsVimentin expression was evaluated using immunohistochemistry in 1483 patients diagnosed with endometrial cancer across 14 hospitals in Europe. Expression levels of vimentin were analyzed in conjunction with clinical characteristics for predicting disease-specific survival and lymph node metastases.ResultsVimentin loss was significantly associated with aggressive disease and poor survival. Adjusted for clinicopathological variables, vimentin remained independently prognostic with a hazard ratio (HR) of 1.68 (95% CI 1.16–2.42, P = 0.006). Vimentin expression remained independently prognostic in endometrioid endometrial cancer- and FIGO staged 1 patient. Interestingly, vimentin loss independently predicted lymph node metastases, with an HR of 1.83 (95% CI 1.13–2.95, P = 0.014).ConclusionsLoss of vimentin in preoperative biopsies serves as an independent predictor of poor prognosis and lymph node metastases. Incorporating vimentin as a clinical marker can improve risk stratification and treatment decisions.

SERPINA1 promotes the invasion, metastasis, and proliferation of pancreatic ductal adenocarcinoma via the PI3K/Akt/NF-κB pathway

Serpin peptidase inhibitor clade A member 1 (SERPINA1) is highly expressed in a variety of solid tumors. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here, we report evidence that SERPINA1 acts as a potent oncogene to drive its extremely malignant character. We found that elevated SERPINA1 expression in primary tumors was associated with lymph node metastasis and shorter survival in PDAC patients. Mechanistic investigations revealed that overexpression of SERPINA1 induced nuclear translocation and phosphorylation of the p65 subunit through the PI3K/Akt/NF-κB pathway, thereby promoting the invasion, metastasis and proliferation of PDAC cells in vitro and in vivo. Conversely, the knockdown of SERPINA1 attenuated this signaling pathway and restored the phenotype of PDAC cells overexpressing SERPINA1. Overall, our study reveals that SERPINA1 affects the properties of PDAC through the PI3K/Akt/NF-κB pathway, and its activation confers the clinical features of epithelial-mesenchymal transition and proliferation in the disease.

CircLPHN3 correlates with prognosis in colorectal cancer and regulates cellular processes by targeting miR-142-5p.

Colorectal cancer (CRC) is often diagnosed late and has a poor prognosis. Circular RNAs (circRNAs) have been identified as prognostic biomarkers in various cancers, including CRC. The objective was to elucidate the role of circLPHN3 (hsa_circ_0069865) in CRC progression and to provide a promising prognostic marker for CRC. CircLPHN3 was identified through bioinformatics analysis of the GSE121842 dataset. The levels of circLPHN3 in CRC samples were analyzed by real time-quantitative polymerase chain reaction. Its clinical significance was assessed using the Kaplan-Meier curve and multivariate Cox regression. Downstream microRNAs of circLPHN3 were predicted with the RNAhybrid, Circular RNA Interactome, and starBase online databases. The target of miR-142-5p was predicted using miRDB, TargetScanHuman, starBase, and miRWalk databases. The relationship between circLPHN3, miR-142-5p, and LDB2 was verified by dual luciferase reporter assay. The function of circLPHN3 on CRC cell growth and metastasis was measured using Transwell and the cell counting kit-8 assay. Significant downregulation of circLPHN3 was found in CRC. CircLPHN3 was closely related to higher tumor node metastasis stage, lymph node metastasis, and predicted unfavorable prognosis. miR-142-5p was highly expressed in CRC and its expression was negatively regulated by circLPHN3. Overexpression of circLPHN3 curbed CRC cell growth, migration, and invasion, mediated by miR-142-5p. Moreover, LDB2 was identified as a target of miR-142-5p. CircLPHN3 acted as a prognostic biomarker and tumor suppressor for CRC via modulating miR-142-5p.

Roles of Chemokine Axes in Breast Cancer.

Chemokines bind to specific chemokine receptors, known as cell surface G protein-coupled receptors, constructing chemokine axes which lead to cell migration and invasion in developmental stage, pathophysiological process, and immune reactions. The chemokine axes in the tumor microenvironment are involved in tumor growth, angiogenesis, cancer stem-like cell properties, metastasis, and chemoresistance, modifying tumor immune contexture and cancer progression. Clinical features, including tumor state, grade, lymph node metastasis, and cancer subtypes, are related to the specific chemokine axes, which play a significant role in immune contexture and cell to cell interaction in the tumor microenvironment, followed by altered cancer prognosis and overall survival. The present review summarizes the role of chemokine axes in breast cancer, based on data obtained from cell line and animal models and human tumor samples. This review provides information that understand the important roles of each chemokine axis in breast cancer, probably offering a clue of adjuvant therapeutic options to improve the quality of life and survival for patients with breast cancer.