Occurrence Of Lymph Node Metastasis Research Articles

Involvement of TGFBI-TAGLN axis in cancer stem cell property of head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a significant healthcare burden globally. Previous research using single-cell transcriptome analysis identified TGFBI as a crucial marker for the partial-epithelial-mesenchymal transition (partial-EMT) program. However, the precise role of TGFBI in HNSCC progression remains unclear. Therefore, our study aimed to clarify the impact of TGFBI on the malignant behavior of HNSCC cells. Through RNA-sequencing data from the TCGA database, we validated that increased TGFBI expression correlates with a higher occurrence of lymph node metastasis and unfavorable prognosis in HNSCC cases. Functional experiments demonstrated that TGFBI overexpression enhances the ability of sphere formation, indicating stem-cell-like properties. Conversely, TGFBI depletion reduces sphere formation and suppresses the expression of cancer stem cell (CSC) markers. RNA-sequencing analysis of TGFBI-overexpressing and control HNSCC cells revealed TAGLN as a downstream effector mediating TGFBI-induced sphere formation. Remarkably, TAGLN depletion abolished TGFBI-induced sphere formation, while its overexpression rescued the suppressed sphere formation caused by TGFBI depletion. Moreover, elevated TAGLN expression showed correlations with the expression of TGFBI and partial-EMT-related genes in HNSCC cases. In conclusion, our findings suggest that TGFBI may promote CSC properties through the upregulation of TAGLN. These novel insights shed light on the involvement of the TGFBI-TAGLN axis in HNSCC progression and hold implications for the development of targeted therapies.

Prediction models for lymph node metastasis in cervical cancer based on preoperative heart rate variability.

The occurrence of lymph node metastasis (LNM) is one of the critical factors in determining the staging, treatment and prognosis of cervical cancer (CC). Heart rate variability (HRV) is associated with LNM in patients with CC. The purpose of this study was to validate the feasibility of machine learning (ML) models constructed with preoperative HRV as a feature of CC patients in predicting CC LNM. A total of 292 patients with pathologically confirmed CC admitted to the Department of Gynecological Oncology of the First Affiliated Hospital of Bengbu Medical University from November 2020 to September 2023 were included in the study. The patient' preoperative 5-min electrocardiogram data were collected, and HRV time-domain, frequency-domain and non-linear analyses were subsequently performed, and six ML models were constructed based on 32 parameters. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Among the 6 ML models, the random forest (RF) model showed the best predictive performance, as specified by the following metrics on the test set: AUC (0.852), accuracy (0.744), sensitivity (0.783), and specificity (0.785). The RF model built with preoperative HRV parameters showed superior performance in CC LNM prediction, but multicenter studies with larger datasets are needed to validate our findings, and the physiopathological mechanisms between HRV and CC LNM need to be further explored.

Predictive value of machine learning models for lymph node metastasis in gastric cancer: A two-center study.

Gastric cancer is one of the most common malignant tumors in the digestive system, ranking sixth in incidence and fourth in mortality worldwide. Since 42.5% of metastatic lymph nodes in gastric cancer belong to nodule type and peripheral type, the application of imaging diagnosis is restricted. To establish models for predicting the risk of lymph node metastasis in gastric cancer patients using machine learning (ML) algorithms and to evaluate their predictive performance in clinical practice. Data of a total of 369 patients who underwent radical gastrectomy at the Department of General Surgery of Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) from March 2016 to November 2019 were collected and retrospectively analyzed as the training group. In addition, data of 123 patients who underwent radical gastrectomy at the Department of General Surgery of Jining First People's Hospital (Jining, China) were collected and analyzed as the verification group. Seven ML models, including decision tree, random forest, support vector machine (SVM), gradient boosting machine, naive Bayes, neural network, and logistic regression, were developed to evaluate the occurrence of lymph node metastasis in patients with gastric cancer. The ML models were established following ten cross-validation iterations using the training dataset, and subsequently, each model was assessed using the test dataset. The models' performance was evaluated by comparing the area under the receiver operating characteristic curve of each model. Among the seven ML models, except for SVM, the other ones exhibited higher accuracy and reliability, and the influences of various risk factors on the models are intuitive. The ML models developed exhibit strong predictive capabilities for lymph node metastasis in gastric cancer, which can aid in personalized clinical diagnosis and treatment.

Diagnostic value of applying preoperative breast ultrasound and clinicopathologic features to predict axillary lymph node burden in early invasive breast cancer: a study of 1247 patients.

Since the Z0011 trial, the assessment of axillary lymph node status has been redirected from the previous assessment of the occurrence of lymph node metastasis alone to the assessment of the degree of lymph node loading. Our aim was to apply preoperative breast ultrasound and clinicopathological features to predict the diagnostic value of axillary lymph node load in early invasive breast cancer. The 1247 lesions were divided into a high lymph node burden group and a limited lymph node burden group according to axillary lymph node status. Univariate and multifactorial analyses were used to predict the differences in clinicopathological characteristics and breast ultrasound characteristics between the two groups with high and limited lymph node burden. Pathological findings were used as the gold standard. Univariate analysis showed significant differences in ki-67, maximum diameter (MD), lesion distance from the nipple, lesion distance from the skin, MS, and some characteristic ultrasound features (P < 0.05). In multifactorial analysis, the ultrasound features of breast tumors that were associated with a high lymph node burden at the axilla included MD (odds ratio [OR], 1.043; P < 0.001), shape (OR, 2.422; P = 0.0018), hyperechoic halo (OR, 2.546; P < 0.001), shadowing in posterior features (OR, 2.155; P = 0.007), and suspicious lymph nodes on axillary ultrasound (OR, 1.418; P = 0.031). The five risk factors were used to build the predictive model, and it achieved an area under the receiver operating characteristic (ROC) curve (AUC) of 0.702. Breast ultrasound features and clinicopathological features are better predictors of high lymph node burden in early invasive breast cancer, and this prediction helps to develop more effective treatment plans.

Association of circulating tumor DNA (ctDNA) molecular disease (MRD) detection with lymph node metastasis after local excision of pathological T1 colorectal cancer: First results from DENEB, a CIRCULATE-Japan GALAXY substudy.

23 Background: Patients with pathological T1 (pT1) colorectal cancer (CRC) at high risk for lymph node metastasis (LNM) after complete local resection are recommended to receive additional intestinal resection along with lymph node dissection. However, the existing pathological criteria for risk stratification of LNM are inadequate, such that ~90% of patients without LNM are exposed to potentially unnecessary treatment. Based on the CIRCULATE-Japan platform, we launched DENEB, a new prospective substudy within the GALAXY observational study, to explore the ability of predicting LNM using circulating tumor DNA (ctDNA) detection compared to the standard pathological criteria. Methods: This study included patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk-stratification criteria for LNM. The additional surgery was indicated for patients meeting any of the following criteria: (1) depth of submucosal invasion (&gt;1000µm); (2) lymphovascular invasion; (3) poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous carcinoma; and (4) high-grade tumor budding (BD2/3) at the site of deepest invasion according to the Japanese guideline. ctDNA was analyzed from plasma samples collected within 4 weeks before the additional intestinal resection using a personalized, tumor-informed assay (Signatera bespoke multiplex-PCR NGS assay). The study assessed the diagnostic concordance rate between ctDNA detection and the occurrence of LNM. Results: Of 208 CRC patients enrolled between July 2021 and May 2023 in DENEB, 166 patients met the inclusion criteria. Of these, 22 (13.3%) were ultimately diagnosed with pStage III due to the presence of LNM in additional intestinal resection. Among the 166 patients, 6 patients tested ctDNA-positive; all 6 had LNM, yielding a positive predictive value of 100.0%. On the other hand, 160 patients had ctDNA-negative results, 144 of whom did not have LNM, resulting in a negative predictive value of 90.0%. The overall diagnostic concordance rate for ctDNA in detecting LNM was 90.4% (95% confidence interval, 84.8% to 94.4%). All 6 patients with a ctDNA-positive result and LNM had left-sided colorectal cancer and a tumor diameter greater than 13 mm. Conclusions: This analysis showed that ctDNA testing has the potential to improve risk stratification of LNM in patients with pT1 CRC who underwent complete local resection. Clinical trial information: UMIN000039205 .

Six Transmembrane Epithelial Antigen 1 as a Prognostic Biomarker in Carcinomas: A Meta-Analysis.

Six transmembrane epithelial antigen 1 (STEAP1) is aberrantly expressed in cancers and could therefore be a potential biomarker. This study examined the connection between STEAP1 expression and clinical features/prognosis in cancer patients. Several databases were comprehensively searched for related published studies. The combination of hazard ratios (HRs), odd ratios (ORs), and 95% confidence intervals (95% CIs) was used to assess the role of STEAP1. The Cancer Genome Atlas (TCGA) dataset was used to estimate the prognostic value of STEAP1 in multiple cancer types, and several biological behaviors related to STEAP1 were evaluated by CancerSEA. Searches of electronic databases revealed 7 relevant trials with 765 patients. A significant connection was found between high STEAP1 expression and worse overall survival amongst cancer patients (HR = 1.87, 95% CI: 1.49-2.34, p < 0.001). In addition, a strong correlation was found between high STEAP1 expression and the occurrence of lymph node metastases (OR = 3.19, 95% CI: 1.26-8.09, p < 0.001). Analysis of TCGA datasets verified that a higher level of STEAP1 expression is linked with reduced survival in many kinds of cancer. At the single cell level, STEAP1 expression was correlated with some tumor biological behaviors, such as angiogenesis, quiescence, and stemness. STEAP1 could regulate various biological functions in tumors and predict prognosis as a novel biomarker in a number of cancer types.

Clinical value of hemoglobin, albumin, lymphocyte, and platelet indexes in predicting lymph node metastasis and recurrence of endometrial cancer: a retrospective study.

To study the clinical importance of hemoglobin, albumin, lymphocyte, and platelet (HALP) indexes in predicting lymph node metastasis and recurrence of endometrial cancer. From July 2016 to July 2020, 158 patients suffering from endometrial cancer who visited the gynecology department of General Hospital of Ningxia Medical University from were collected. Employing the X-Tiles program, the ideal HALP cut-off value was established, and the patients were separated into low and high HALP groups. Univariate and multivariate analysis were used to determine the relationship between HALP score and lymph node metastasis and recurrence of endometrial cancer. The optimal cut-off value of HALP score was established to be 22.2 using X-Tiles software, and the patients were separated into high HALP group (HALP score > 22.2, with 43 cases) and low HALP group (HALP score ≤ 22.2, 115 cases). Endometrial cancer patients' HALP scores were strongly connected with differentiation, the degree of myometrial invasion, and lymph node metastasis (P < 0.05), although not with age, menopausal status, or stage (P > 0.05). Multivariate logistic regression analysis revealed that the HALP score (OR = 2.087) was the influencing factor for lymph node metastasis (P < 0.05). The ROC curve suggested that the AUC of HALP score in predicting lymph node metastasis was 0.871, which had high diagnostic value. When compared to patients without recurrence, HALP scores of patients with recurrence were considerably lower (P < 0.05). Multivariate logistic regression analysis showed that HALP score (OR = 2.216) was the influencing factor for the occurrence of lymph node metastasis (P < 0.05). The ROC curve suggested that the AUC of HALP score in predicting relapse was 0.855, with high diagnostic value. The HALP score shows good predictive performance in predicting lymph node metastasis and recurrence of endometrial cancer, and has high clinical value, which helps in improving the accuracy and effectiveness of clinical diagnosis and prognosis research.

Lymph node metastasis and its risk factors in T1 lung adenocarcinoma.

In this study, the focus was primarily on examining the occurrence of lymph node metastasis in T1 lung adenocarcinoma, while also analyzing the relationship between clinical variables such as imaging characteristics, pathological classifications, and lymph node metastasis. We retrospectively analyzed data from patients with T1 lung adenocarcinoma who underwent lobectomy and lymph node dissection between January 2016 and December 2019. Utilizing univariate and multivariate analyses, we assessed the associations between lymph node metastasis and various clinical factors, including imaging characteristics, lesion location and depth, and pathological subtypes. Of the 433 patients with T1 lung adenocarcinoma, 139 had lymph node metastasis. Moreover, the incidence of node 1 (N1) lymph node, sequential, and node 2 (N2) skip metastases were 12.2%, 12.7%, and 7.2%, respectively. Univariate analysis revealed that tumor diameter, depth ratio, sex, invasive imaging features, and pathological subtype were significantly associated with lymph node metastasis. Multivariate analysis revealed that the tumor depth ratio, tumor diameter, pleural indentation or traction sign, nonvascular penetration sign, solid component, nonadherence, and micropapillary pathological subtype were risk factors for lymph node metastasis. In the multivariate analysis, the micropapillary pathological subtype was an independent risk factor for N2 skip metastasis. In patients with clinical stage T1 lung adenocarcinoma, the risk of lymph node metastasis is higher for tumors located deep within the lung tissue with solid components, invasive preoperative imaging features, and larger diameters. For N2 skip lymph node metastasis, the micropapillary pathological subtype represents a significant high-risk factor.

Predicting Lymph Node Metastasis From Primary Cervical Squamous Cell Carcinoma Based on Deep Learning in Histopathologic Images

We developed a deep learning framework to accurately predict the lymph node status of patients with cervical cancer based on hematoxylin and eosin–stained pathological sections of the primary tumor. In total, 1524 hematoxylin and eosin–stained whole slide images (WSIs) of primary cervical tumors from 564 patients were used in this retrospective, proof-of-concept study. Primary tumor sections (1161 WSIs) were obtained from 405 patients who underwent radical cervical cancer surgery at the Fudan University Shanghai Cancer Center (FUSCC) between 2008 and 2014; 165 and 240 patients were negative and positive for lymph node metastasis, respectively (including 166 with positive pelvic lymph nodes alone and 74 with positive pelvic and para-aortic lymph nodes). We constructed and trained a multi-instance deep convolutional neural network based on a multiscale attention mechanism, in which an internal independent test set (100 patients, 228 WSIs) from the FUSCC cohort and an external independent test set (159 patients, 363 WSIs) from the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program database were used to evaluate the predictive performance of the network. In predicting the occurrence of lymph node metastasis, our network achieved areas under the receiver operating characteristic curve of 0.87 in the cross-validation set, 0.84 in the internal independent test set of the FUSCC cohort, and 0.75 in the external test set of the Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma cohort of the Cancer Genome Atlas program. For patients with positive pelvic lymph node metastases, we retrained the network to predict whether they also had para-aortic lymph node metastases. Our network achieved areas under the receiver operating characteristic curve of 0.91 in the cross-validation set and 0.88 in the test set of the FUSCC cohort. Deep learning analysis based on pathological images of primary foci is very likely to provide new ideas for preoperatively assessing cervical cancer lymph node status; its true value must be validated with cervical biopsy specimens and large multicenter datasets.

Surgical Management of Indeterminate Thyroid Nodules across Different World Regions: Results from a Retrospective Multicentric (the MAIN-NODE) Study.

Indeterminate thyroid nodules (ITNs) are characterized by an expected malignancy ranging from 5% to 30%, with most patients undergoing a diagnostic, rather than therapeutic, operation. The aim of our study was to compare the approach to ITNs across different regions of the world. In this retrospective, multicentric, international study, according to the WHO classification, we identified the South East Asian Region (SEAR), the Americas Region (AMR), the Eastern Mediterranean Region (EMR), the Europe Region (EUR), and the Western Pacific Region (WPR). One high-volume thyroid centre was included for each region. Demographic, preoperative, and pathologic data were compared among the different regions. Overall, 5737 patients from five high-volume thyroid centres were included in this study. We found that the proportion of ITNs over the global activity for thyroid disease was higher in the EUR (37.6%) than in the other regions (21.1-23.6%). In the EMR, the patients were significantly younger (with a mean of 43.1 years) than in the other regions (range, 48.8-57.4 years). The proportion of lobectomy was significantly higher in the WPR, where 83.2% (114/137) of patients received this treatment, than in the other regions, where lobectomies were performed in 44.1-58.1% of patients. The pathological diagnosis of malignancy was significantly higher in the SEAR centre, being over 60%, than in centres of the other regions, where it ranged from 26.3% to 41.3%. The occurrence of lymph node metastases was higher in the WPR (27.8%), AMR (26.9%), and EMR (20%) centres than in the EUR and SEAR centres, where it was lower than 10%. In summary, we found in our study different approaches and outcomes in the diagnosis and treatment of ITNs among countries. Overall, almost 60% of patients with ITNs who underwent surgery actually presented a benign disease, potentially undergoing an unnecessary operation.

N-Cadherin Expression with Metastasis of Neck Lymph Nodes in Patients with Nasopharyngeal Carcinoma.

Lymph node (LN) metastases were one characteristic of negative progress of NPC patient despite its advanced therapeutic approaches. One mechanism for the occurrence of epithelial to mesenchymal transition (EMT)-mediated metastases is by increasing N-cadherin expression. The purpose of this research is to determine investigating N-cadherin expression against metastatic LN in NPC cases. Samples were taken by unproportionate stratified random sampling. N-cadherin expression was examined using immunohistochemistry methods. N-cadherin expression was assessed visually by binocular light microscopy. We analyzed these data using Mann-Whitney U-test to examine N-cadherin expression and lymph node metastases. A strong expression was found in N3 group by 63.6%; 27.3% in the N2 group and 9.1% in the N1 group. In patients with NPC N0 or without lymph node metastases, N-cadherin expression is 0%. The expression of N-cadherin is indeed an indicator of the occurrence of lymph node metastases in NPC with a statistically significant analysis of p = 0.026 (p < 0.05). There were correlations between N-cadherin expression and lymph node metastasis on NPC patients.

Fibroblast growth factor 2 expression on lymph node metastasis in early-stage breast cancer

Introduction: Axillary lymph node involvement is an important aspect of breast cancer diagnosis in determining treatment and predicting distant metastasis. Lymph node metastasis is associated with higher recurrence and survival rates. Lymph node status is a significant prognostic factor and is widely used. Several factors affect lymph node metastasis, including tumor size, grade, and invasive ductal histological type. FGF2, a lymphangiogenesis factor, influences the occurrence of lymph node metastasis. The present study aimed to determine the association between FGF2 expression and axillary lymph node metastasis in early-stage breast cancer and evaluate the association between FGF2 expression and clinicopathologic factors. Methods: A cross-sectional design was used to evaluate the expression of FGF2 in 47 early-stage breast cancer patients who underwent either a mastectomy or breast-conserving surgery procedure at Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, from January 2014 to December 2018. FGF2 expression was examined by immunohistochemistry. Results: FGF2 expression was significantly correlated with axillary lymph node metastasis incidence [p = 0.044, odds ratio 4.22 (95% CI 0.983-18.1)]. Higher FGF2 expression was significantly correlated with the grade, subtype, estrogen receptor (ER) status, and progesterone receptor (PR) status of the tumor (p = 0.017, p = 0.031, p = 0.002, p = 0.013, respectively). Conclusions: Increased FGF2 expression and tumor size significantly correlated with axillary lymph node metastasis. The tumor's grade, intrinsic subtype, ER and PR status were significantly correlated with increased FGF2 expression. Our study indicated that FGF2 expression might aid in determining the presence of axillary lymph node metastasis.

Prognostic Ability of Tumor Budding Outperforms Poorly Differentiated Clusters in Gastric Cancer.

Simple SummarySmall clusters of tumor cells at the invasion front of the tumor, known as “tumor budding” and larger clusters of cells, known as “poorly differentiated clusters”, are well known histological parameters to assess the outcome of colorectal cancer. However, their prognostic value for gastric cancer is less well investigated and controversial based on the studies conducted so far. In our retrospective study, we investigated the prognostic power of these two entities in a large cohort of gastric cancer patients. Our results demonstrate that tumor budding is an independent prognostic factor determining overall survival in gastric cancer, especially in intestinal type adenocarcinomas. In addition, budding can also predict the risk of lymph node metastases. However, although the trend is similar for poorly differentiated clusters, their predictive value is lower and they have not been shown to be an independent prognostic factor of survival in gastric cancer.The prognostic value of histological phenomena tumor budding (TB) and poorly differentiated clusters (PDCs) have been less studied in gastric cancer (GAC) and the data provided so far are controversial. In our study, 290 surgically resected GAC cases were evaluated for TB according to the criteria of International Tumor Budding Consensus Conference (ITBCC) and PDC, and both parameters were scored on a three-grade scale as described for colorectal cancer previously (0: Grade0, 1–4: Grade1, 5–9: Grade2 and ≥10: Grade3) and classified as low (Grade0–2) and high (Grade3) TB/PDC. High TB/PDC was associated with diffuse-type morphology, higher pT status, incomplete surgical resection, poor tumor differentiation and perineural and lymphovascular invasion. Multivariable survival analyses have shown an independent prognostic role of high TB with poorer overall survival in the total cohort (p = 0.014) and in intestinal-type adenocarcinomas (p = 0.005). Multivariable model revealed high TB as an independent predictor for lymph node metastasis in both the total cohort (p = 0.019) and in the intestinal type adenocarcinomas (p = 0.038). In contrast to tumor budding, no significant association was found between PDC and the occurrence of lymph node metastasis and tumor stage and even survival. In conclusion, tumor budding is an independent prognostic factor of survival in gastric cancer, especially in intestinal-type adenocarcinomas.

Evaluation of Risk Factors for Distant and Lymph Node Metastasis of Pancreatic Neuroendocrine Tumors.

PurposeMetastases of pancreatic neuroendocrine tumors (pNETs) can be found at the time of diagnosis in 20–50% of cases. Small asymptomatic tumors may be left for observation; however, they can metastasize. The aim of the study was to evaluate risk factors for distant and lymph node metastases of pNETs.Patients and methodsOne hundred and fourteen patients with postoperatively confirmed pNET were analyzed retrospectively in a single ENETS Center of Excellence. The relationship between location, size, differentiation of the tumor, and occurrence of lymph node and distant metastases was analyzed.ResultspNETs’ location was pancreatic head – 38 (33.3%), body or tail – 68 (59.7%), and 8 (7.0%) involved the entire organ. Fifty-six (49.1%) tumors were graded G1, 50 (43.9%) G2, and 8 (7.0%) G3. Seventy-two (63.2%) tumors were ≥2 cm in diameter, and 42 (36.8%) <2 cm. Twenty-two (19.3%) patients had distant metastases and 47 (41.2%) had lymph node metastases. In ≥2 cm tumors distant and lymph node metastases were more frequent (p < 0.05). Distant metastases incidence was significantly higher in distally located tumors (p = 0.01) and in G2 and G3 tumors (p < 0.01). In 9.5% of <2cm tumors, distant metastases were present at diagnosis.ConclusionDistant metastases are more often found in larger, distally located pNETs grade G2 and G3, while a higher occurrence of lymph node metastases seems to be associated only with larger tumor size. A considerable number of tumors <2 cm in size have distant metastases already at the diagnosis, which might indicate the need for careful qualification of smaller lesions for observation.

SENP1 Aberrance and Its Linkage to Clinical Features, Adjuvant Regimen, and Prognosis in Patients With Surgical Non-small Cell Lung Cancer Receiving Adjuvant Chemotherapy.

BackgroundSmall ubiquitin-like modifier-specific protease 1 (SENP1) plays vital roles in cancer progression and chemoresistance, but its prognostic value in non-small cell lung cancer (NSCLC) is vague. This study aimed to explore the correlation of SENP1 with clinical features, adjuvant chemotherapy regimen, and prognosis in patients with surgical NSCLC receiving adjuvant chemotherapy.MethodsTumor and adjacent tissues were collected from 157 patients with surgical NSCLC receiving adjuvant chemotherapy. Meanwhile, tumor tissue and paired adjacent tissue specimens were obtained to evaluate SENP1 protein expression by immunohistochemistry (IHC) assay; among which, 102 pairs were used to detect SENP1 messenger RNA (mRNA) by reverse transcription quantitative PCR.ResultsSENP1 IHC score and SENP1 mRNA expression were increased in tumor tissue than adjacent tissue (p < 0.001). Besides, elevated SENP1 IHC score was correlated with > 5 cm tumor size (p = 0.045), lymph node metastasis occurrence (p = 0.003), and advanced tumor-node-metastasis (TNM) stage (p = 0.012); meanwhile, increased SENP1 mRNA expression was associated with histopathological subtype (p = 0.011), lymph node metastasis occurrence (p = 0.008), and higher TNM stage (p = 0.015). Besides, no correlation was found in SENP1 IHC score (p = 0.424) or mRNA expression (p = 0.927) with specific adjuvant chemotherapy regimen. Additionally, both the SENP1 protein (high) (p = 0.003) and mRNA high (p = 0.028) were correlated with poor disease-free survival (DFS), while SENP1 protein high was also associated with shorter overall survival (OS) (p = 0.029). Furthermore, SENP1 protein (high vs. low) was independently associated with unsatisfying DFS [p = 0.009, hazard ratio (HR) = 1.798] and OS (p = 0.049, HR = 1.735).ConclusionSENP1 may serve as a potential biomarker to improve the management of patients with surgical NSCLC receiving adjuvant chemotherapy.

The Role of the Adipokine Resistin in the Pathogenesis and Progression of Epithelial Ovarian Cancer.

Obesity is a civilization disease associated with an increased risk of developing cardiovascular diseases, diabetes, and some malignancies. The results concerning the relationship between obesity and epithelial ovarian cancer (EOC) are inconclusive. The higher incidence of neoplasms in obese subjects has led to the development of the adipokine hypothesis. Omental adipocyte cells interact with cancer cells, promoting their migration and metastasis via the secretion of adipokines, growth factors, and hormones. One of the adipokines is resistin. It was shown in vitro that resistin stimulates the growth and differentiation of ovarian cancer cells. Moreover, it increases the level of angiogenesis factors, e.g., matrix metalloproteinase 2 (MMP-2) and vascular epithelial growth factor (VEGF). Additionally, resistin induces epithelial–mesenchymal transition (EMT) and stemness in EOC cell lines. A positive correlation has been shown between a higher level of resistin expression and the stage of histological differentiation of EOC or the occurrence of lymph node metastases. In addition, the overexpression of resistin has been found to act as an independent factor determining disease-free survival as well as overall survival in EOC patients. Growing evidence supports the finding that resistin plays an important role in some mechanisms leading to the progression of EOC, though this issue still requires further research.

The Construction and Development of a Clinical Prediction Model to Assess Lymph Node Metastases in Osteosarcoma.

Background: This study aimed to construct a clinical prediction model for osteosarcoma patients to evaluate the influence factors for the occurrence of lymph node metastasis (LNM).Methods: In our retrospective study, a total of 1,256 patients diagnosed with chondrosarcoma were enrolled from the SEER (Surveillance, Epidemiology, and End Results) database (training cohort, n = 1,144) and multicenter dataset (validation cohort, n = 112). Both the univariate and multivariable logistic regression analysis were performed to identify the potential risk factors of LNM in osteosarcoma patients. According to the results of multivariable logistic regression analysis, A nomogram were established and the predictive ability was assessed by calibration plots, receiver operating characteristics (ROCs) curve, and decision curve analysis (DCA). Moreover, Kaplan-Meier plot of overall survival (OS) was plot and a web calculator visualized the nomogram.Results: Five independent risk factors [chemotherapy, surgery, lung metastases, lymphatic metastases (M-stage) and tumor size (T-stage)] were identified by multivariable logistic regression analysis. What's more, calibration plots displayed great power both in training and validation group. DCA presented great clinical utility. ROCs curve provided the predictive ability in the training cohort (AUC = 0.805) and the validation cohort (AUC = 0.808). Moreover, patients in LNN group had significantly better survival than that in LNP group both in training and validation group.Conclusion: In this study, we constructed and developed a nomogram with risk factors, which performed well in predicting risk factors of LNM in osteosarcoma patients. It may give a guide for surgeons and oncologists to optimize individual treatment and make a better clinical decision.

Correlation between Pre-Operative 25-Hydroxyvitamin D Levels and Poor Prognostic Factors for Papillary Thyroid Cancer

Purpose To evaluate the relationship between pre-operative 25-hydroxyvitamin D (25 (OH) D) levels and poor prognostic factors for papillary thyroid cancer (PTC). Methods A total of 1161 patients diagnosed with PTC were analyzed retrospectively. The patients were categorized .based on their pre-operative 25 (OH) D levels into three groups: the severe vitamin D deficiency (VDD) group (25 (OH) D < 10 ng/mL), moderate VDD group (20 ng/mL > 25 (OH) D ≥ 10 ng/mL), and control group (25(OH)D ≥ 20 ng/mL) Differences in the demographic and clinicopathological characteristics among the three groups were analyzed. Linear and logistic regression analyses were also performed to determine the effect of 25 (OH) D levels on the established poor prognostic factors for PTC. Results We observed a negative correlation between 25 (OH) D levels and tumor size (r = −0.067, P = 0.049). Severe VDD and moderate VDD were independently associated with lymph node metastasis and distant metastasis diagnosed during surgery (P = 0.00, odds ratio (OR) = 4.11; P = 0.00, OR = 3.33, respectively). After adjusting parameters such as sex, age, body mass index, and thyroid-stimulating hormone (TSH) levels, severe VDD and moderate VDD were found to be closely associated with advanced cancer stage (stage III or IV) (P = 0.018, OR = 3.02; P = 0.041, OR = 3.60, respectively). Additionally, a significant correlation (P = 0.007) was observed between the pre-operative 25 (OH) D and TSH levels. Conclusion 25 (OH) D levels were significantly associated with certain poor prognostic factors for PTC, including larger tumor diameter and the occurrence of lymph node metastasis. More prospective studies are needed to evaluate whether the assessment and supplementation of vitamin D contributes to the pre-operative management of patients with PTC.

14-3-3ζ promoted invasion and lymph node metastasis of breast invasive ductal carcinoma with HER2 overexpression

BackgroundHER2 was a recognized oncogene that promoted the development and metastasis of breast cancer, but its positive expression rate in invasive ductal carcinoma (IDC) was much lower than that in ductal carcinoma in situ (DCIS). The correlation between the occurrence and development of breast cancer and the amplification and overexpression of HER2 gene alone was still controversial. 14–3–3ζ had a strong protein binding ability and a variety of functions, mainly through the interaction with other proteins to exert its unique biological activities. However, influence and interaction relationship of the two proteins on the development of IDC was not clear. Furthermore, the mutual effect mechanism of synergy effect on lymph node metastasis of IDC was not known well too. MethodsImmunohistochemistry experiment was performed to detect expression status of 14–3–3ζ, HER2, TGF-β, p53 and Gli2 in paraffin-embedded samples respectively, including 30 cases of normal breast tissue, 30 cases of usual ductal hyperplasia (UDH), 30 cases of atypical ductal hyperplasia (ADH), 30 cases of DCIS and 120 cases of IDC. ResultsThe positive expression rates of 14–3–3ζ/HER2 in Normal group, UDH group, ADH group, DCIS group and IDC group were 30%/0.00%, 26.7%/0.00%, 53.3%/33.3%, 46.7%/53.3% and 50%/24.2%, respectively. Compared with Normal group or UDH group, the expression of 14–3–3ζ was significantly increased in ADH, DCIS and IDC groups. 14–3–3ζ was overexpressed in only 4 of the 16 DCIS cases with HER2 overexpression (25.0%, 4/16), but it was overexpressed in 7 of the 9 IDC cases with DCIS (77.8%, 7/9). Among HER2 overexpression cases, 14–3–3ζ overexpression was significantly different between DCIS group and IDC with DCIS group (P = 0.017). In 18 IDC cases with lymph node metastasis and HER2 overexpression, 14–3–3ζ was overexpressed in 15 cases (83.3%, 15/18), while in the 11 IDC cases without lymph node metastasis, 14–3–3ζ and HER2 were overexpressed in only 5 cases (45.5%, 5/11). Co-overexpression of 14–3–3ζ and HER2 was positively correlated with occurrence of lymph node metastasis (P = 0.048). TGF-β was overexpressed in both precancerous lesion group and IDC group compared with normal group. Compared with the IDC group without lymph node metastasis, TGF-β expression was significantly increased in the IDC group with lymph node metastasis (P = 0.015). In IDC cases with 14–3–3ζ and HER2 co-overexpression, the expression of p53 in IDC with lymph node metastasis was significantly decreased (P = 0.010), while the expression of Gli2 was significantly increased compared with IDC cases without lymph node metastasis (P = 0.038). The co-overexpression of 14–3–3ζ and HER2 was positively correlated with ER negative expression (P < 0.001) and PR negative expression (P = 0.038), respectively. Conclusion14–3–3ζ synergistic with HER2 could promote the occurrence and development of breast IDC and induce the lymph node metastasis of IDC, suggesting that combined overexpression of 14–3–3ζ and HER2 would lead to higher invasion and metastasis risk of breast cancer. It was speculated that the combined detection of 14–3–3ζ and HER2 would be one of the key factors affecting the clinical treatment decision and prognosis.

Fatty Acid Receptor CD36 Functions as a Surrogate Parameter for Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Simple SummaryThe frequent occurrence of occult cervical lymph node metastasis is still a therapeutic challenge in oral squamous cell carcinoma (OSCC) and represents a limiting factor in terms of survival. The common staging of malignancy is not precise enough to predict the development of lymph node metastases and additional prognostic factors are needed. In this study we show that CD36, a protein related to fatty acid metabolism, is expressed in OSCC and correlates with the occurrence of lymph node metastasis. CD36 may be useful as a specific parameter for lymph node metastasis and as a progression parameter for survival. Therefore, CD36 could be useful for risk stratification regarding lymph node metastasis in OSCC and, beyond that, CD36 could also be a possible therapeutic target in future.Purpose: To investigate the expression pattern of CD36 in a patient population with oral squamous cell carcinoma (OSCC) and to correlate CD36 expression with clinical and histopathological parameters. The hypothesis was that CD36 expression correlates with the occurrence of lymph node metastasis. Methods: To address the study objectives, a retrospective cohort study was conducted. Study variables included demographic, histopathological and survival data. CD36 expression patterns were assessed by immunohistochemistry on tissue microarrays (TMA). Logistic regression analysis, survival analysis and Cox proportional hazards model were performed. Results: High CD36 expression correlated significantly with a higher T-status, grading and occurrence of lymph node metastasis. The logistic regression with binary N status as a dependent variable showed that high CD36 expression increased the chance for lymph node metastasis 45-fold (OR = 44.7, 95% CI: 10.0–316). Patients with high CD36 expression had lower probabilities of progression-free survival. CD36 had a small and non-significant independent influence on progression-free survival. Conclusions: CD36 is expressed in OSCC and correlates with tumor grading, T-status, and especially the occurrence of lymph node metastasis. CD36 may be useful for risk stratification regarding lymph node metastasis in OSCC.