Lymphatic Metastasis In Patients Research Articles

Development of the TP53 mutation associated hypopharyngeal squamous cell carcinoma prognostic model through bulk multi-omics sequencing and single-cell sequencing

ObjectiveThe aim of this study was to construct a prognostic model based on the TP53 mutation to calculate prognostic risk scores of patients with HPSCC. MethodsTP53 mutation and transcriptome data were downloaded from the TCGA databases. Gene expression data from GSE65858, GSE41613, GSE3292, GSE31056, GSE39366, and GSE227156 datasets were downloaded from the GEO database. GSEA, univariate, multivariate Cox analyses, and LASSO analysis were employed to identify key genes and construct the prognostic model. ROC curves were utilized to validate the OS and RFS results obtained from the model. The associations between risk scores with various clinicopathological characteristics and immune scores were analyzed via ggplot2, corrplot package, and GSVA, respectively. Single-cell sequencing data was analyzed via unbiased clustering and SingleR cell annotations. ResultsInitially, two key genes, POLD2 and POLR2G, were identified and utilized to construct the prognostic model. Samples were divided into different risk groups via the risk scores obtained from the model, with high-risk group samples exhibiting poorer prognosis. Furthermore, the risk score exhibited a positive correlation with lymphatic metastasis in patients and the immune scores of CD4+ T, CD8+ T, dendritic cell, macrophage, and neutrophil. The immune responses also exhibited notable disparities between the high- and low-risk groups. The results of single-cell sequencing analysis demonstrated that epithelial cells and macrophages were relatively abundant in HPSCC samples. POLD2 and POLR2G exhibited higher expressions in epithelial cells, with most of the identified pathways also enriched in epithelial cells. ConclusionThe prognostic model exhibited a significant capacity for predicting the prognosis of HSPCC samples based on the TP53 mutation conditions and may also predict the cancer characteristics and immune infiltration scores of samples via different risk scores obtained from the model. Level of evidenceLevel 5.

Clinical importance of serum and pleural fluid prominin-1 and hypoxia-inducible factor-1α concentration in the evaluation of lymph node involvement in patients with malignant pleural effusion.

Malignant pleural effusion (MPE) and lymph node metastasis (LNM) presence are poor prognostic factors that have importance for cancer patients. The study objective was to determine whether hypoxia-inducible factor-1α (HIF-1α) and prominin-1 (CD133) in pleural fluid (P) and serum (S) could be used as biomarkers for diagnosis of lymph node involvement in patients with MPE. Fifty-six patients with MPE and 30 healthy control subjects were included. Computerized tomography (CT) and positron emission tomography (PET) were used to diagnose pleural effusion. Patients with malignant cells in pleural fluid cytological examination were included in the MPE group. Thirty-five patients with lymph node metastases on CT were included in the LNM-positive MPE group. Serum and pleural fluid HIF-1α and CD-133 concentrations were measured manually via enzyme-linked immunosorbent assay (ELISA). Serum concentrations of HIF-1α and CD133 were higher in MPE patients. It was found that CD133/HIF-1α (S) ratio was higher in the malignant patient group with positive lymph node involvement than in the negative group, while concentrations of HIF-1α (P) were lower. Pleural fluid HIF-1α and CD133/HIF-1α (S) ratio had sufficient performance in diagnosing lymphatic metastases in patients with MPE (AUC = 0.90 and 0.83, respectively). In conclusion, serum HIF-1α and CD133 concentrations were higher in patients with MPE, consistent with our hypothesis. Concentrations of HIF-1α (P) and CD133/HIF-1α (S) ratio can be used as biomarkers in diagnosing lymph node involvement in MPE patients, according to this experiment.

Prediction of Response to 177Lu-PSMA Therapy Based on Tumor-to-Kidney Ratio on Pretherapeutic PSMA PET/CT and Posttherapeutic Tumor-Dose Evaluation in mCRPC.

The aim of this study was to analyze the absorbed dose of 177Lu-PSMA in osseous versus lymphatic metastases in patients with metastatic castration-resistant prostate cancer across therapy cycles and to relate those data to therapeutic success. In addition, pretherapeutic prostate-specific membrane antigen (PSMA) PET/CT was evaluated for its ability to predict response behavior. Methods: The study comprised 30 patients with metastatic castration-resistant prostate cancer, each receiving at least 3 cycles of 177Lu-PSMA therapy. Prostate-specific antigen (PSA) values between baseline and 6 wk after the third therapy cycle were used to classify the patients as responders (PSA decline ≥ 50%) or nonresponders (unchanged or increasing PSA level). Quantitative SPECT/CT images were acquired 24, 48, and 168 h after application of 177Lu-PSMA. The absorbed dose for tumor lesions was calculated with dosimetry software. From the pretherapeutic PET/CT scan, the tumor-to-kidney uptake ratio was determined for different SUVs. Results: Regardless of patient response, the kidneys received a mean dose of 0.55 ± 0.20 Gy/GBq per cycle. In the first therapy cycle, the lymph node lesions received a mean dose of 3.73 ± 1.65 Gy/GBq in responders and 1.86 ± 1.25 Gy/GBq in nonresponders (P < 0.01). For bone lesions, the respective mean doses were 3.47 ± 2.00 Gy/GBq and 1.48 ± 0.95 Gy/GBq (P < 0.01). When successive therapy cycles were compared, the mean dose was found to have been reduced from the first to the second cycle by 27% for lymph nodes and by 33% for bone lesions. A significant difference (P < 0.01) in the ratio of lymph node and bone lesion uptake to kidney uptake between responders and nonresponders could be deduced from the pretherapeutic PET/CT scan. Conclusion: Significantly higher doses were achieved for lymph node and bone lesions in responders. The highest absorbed dose, for both lymphatic and osseous lesions, was achieved in the first cycle, decreasing in the second therapy cycle thereafter despite unchanged therapy activities. It may be possible to estimate the response to therapy from the ratio of tumor uptake to kidney uptake obtained from the pretherapeutic PSMA PET/CT scans.

A nomogram-based optimized Radscore for preoperative prediction of lymph node metastasis in patients with cervical cancer after neoadjuvant chemotherapy.

To construct a superior single-sequence radiomics signature to assess lymphatic metastasis in patients with cervical cancer after neoadjuvant chemotherapy (NACT). The first half of the study was retrospectively conducted in our hospital between October 2012 and December 2021. Based on the history of NACT before surgery, all pathologies were divided into the NACT and surgery groups. The incidence rate of lymphatic metastasis in the two groups was determined based on the results of pathological examination following lymphadenectomy. Patients from the primary and secondary centers who received NACT were enrolled for radiomics analysis in the second half of the study. The patient cohorts from the primary center were randomly divided into training and test cohorts at a ratio of 7:3. All patients underwent magnetic resonance imaging after NACT. Segmentation was performed on T1-weighted imaging (T1WI), T2-weighted imaging, contrast-enhanced T1WI (CET1WI), and diffusion-weighted imaging. The rate of lymphatic metastasis in the NACT group (33.2%) was significantly lower than that in the surgery group (58.7%, P=0.007). The area under the receiver operating characteristic curve values of Radscore_CET1WI for predicting lymph node metastasis and non-lymphatic metastasis were 0.800 and 0.797 in the training and test cohorts, respectively, exhibiting superior diagnostic performance. After combining the clinical variables, the tumor diameter on magnetic resonance imaging was incorporated into the Rad_clin model constructed using Radscore_CET1WI. The Hosmer-Lemeshow test of the Rad_clin model revealed no significant differences in the goodness of fit in the training (P=0.594) or test cohort (P=0.748). The Radscore provided by CET1WI may achieve a higher diagnostic performance in predicting lymph node metastasis. Superior performance was observed with the Rad_clin model.

Construction and validation of a nomogram of risk factors and cancer-specific survival prognosis for combined lymphatic metastases in patients with early-onset colorectal cancer.

This study aimed to investigate the risk and prognostic factors of lymph node metastasis (LNM) in early-onset colorectal cancer (EO-CRC) and to develop nomograms for quantitatively predicting LNM and the cancer-specific survival (CSS). A total of 22,405 EO-CRC patients were included in this study using the SEER database from 2010 to 2017. Logistic and Cox regression were used to identify risk and the potential prognostic factors, respectively, for EO-CRC with LNM. Subsequently, nomograms regarding the risk of LNM in EO-CRC patients and its corresponding CSS were constructed based on these factors. The discriminative ability, calibration and clinical usefulness of the nomograms were assessed by the area under the receiver operating characteristic (ROC) curves (AUC), calibration curves, and decision curve analysis (DCA). T-stage and pathological grade were the most represented factors in the predicted LNM nomogram, while histological type and combined distant metastases were the most represented in the nomogram for CSS in EO-CRC patients with LNM (all P < 0.05). The nomogram constructed based on the prognostic factors screened by Cox regression had good performance with C-index of 0.807 and 0.802 for the training and validation cohorts, respectively. The calibration curve showed that the nomograms' predictions were in line with actual observations. Additionally, the ROC curves indicated good discrimination, and the DCA curves implied significant clinical utility of the nomograms. The nomograms we constructed have significant performance in predicting the incidence and prognosis of LNM in EO-CRC patients, which may help clinicians to make better treatment decision making.

CEMIP-mediated hyaluronan metabolism facilitates SCLC metastasis by activating TLR2/c-Src/ERK1/2 axis

Small-cell lung cancer (SCLC) is a highly metastatic and recalcitrant malignancy. Metastasis is the major cause of death in patients with SCLC but its mechanism remains poorly understood. An imbalance of hyaluronan catabolism in the extracellular matrix accelerates malignant progression in solid cancers due to the accumulation of low-molecular-weight HA. We previously found that CEMIP, a novel hyaluronidase, may act as a metastatic trigger in SCLC. In the present study, we found that both CEMIP and HA levels were higher in SCLC tissues than in paracancerous tissues from patient specimens and in vivo orthotopic models. Additionally, high expression of CEMIP was associated with lymphatic metastasis in patients with SCLC, and in vitro results showed that CEMIP expression was elevated in SCLC cells relative to human bronchial epithelial cells. Mechanistically, CEMIP facilitates the breakdown of HA and accumulation of LMW-HA. LMW-HA activates its receptor TLR2, and subsequently recruits c-Src to activate ERK1/2 signalling, thereby promoting F-actin rearrangement as well as migration and invasion of SCLC cells. In addition, the in vivo results verified that depletion of CEMIP attenuated HA levels and the expressions of TLR2, c-Src, and phosphorylation of ERK1/2, as well as liver and brain metastasis in SCLC xenografts. Furthermore, the application of the actin filament inhibitor latrunculin A significantly inhibited the liver and brain metastasis of SCLC in vivo. Collectively, our findings reveal the critical role of CEMIP-mediated HA degradation in SCLC metastasis and suggest its translational potential as an attractive target and a novel strategy for SCLC therapy.

CLIC1 plasma concentration is associated with lymph node metastases in oral squamous cell carcinoma.

Previous studies have shown that the chloride intracellular channel 1 (CLIC1) protein is overexpressed in oral squamous cell carcinoma (OSCC) and nasopharyngeal carcinoma. Patients with these diseases had significantly higher CLIC1 plasma levels than healthy controls. To determine the plasma concentration of CLIC1 in patients with OSCC and laryngeal squamous cell carcinoma (LSCC). We collected blood samples from patients diagnosed with OSCC (n = 13) and LSCC (n = 7), as well as from healthy controls (n = 8). The blood samples were centrifuged to obtain plasma and stored at -80°C. The CLIC1 plasma concentration was determined using enzyme-linked immunosorbent assay (ELISA). The mean CLIC1 plasma concentration was higher in the OSCC group than in the LSCC and control groups. Patients with OSCC and nodal metastases had significantly higher CLIC1 plasma concentration levels than nonmetastatic patients (p < 0.0001; Tukey's multiple comparisons test) and controls (p = 0.0004). The CLIC1 concentration correlated significantly with the presence of nodal spread (p = 0.0003; Spearman's r = 0.8613) and overall TNM staging (p = 0.0167; Spearman's r = 0.6620). No differences in CLIC1 plasma levels were observed between the LSCC and control groups. The CLIC1 plasma concentration was not associated with age, sex, tumor stage, or tumor grade. There were no differences in CLIC1 plasma concentration between healthy controls and patients with LSCC. However, our findings suggest that the presence of this protein in plasma may be associated with lymphatic metastasis in patients with OSCC. More research is needed to confirm this possible association.

The Predicting Role of Serum TSGF and sIL-2R for the Lymph Node Metastasis of Papillary Thyroid Carcinoma.

Objective To explore the clinical utility of tumor-specific growth factor (TSGF) and the soluble interleukin-2 (IL-2) receptor (sIL-2R) as immune-related factors for predicting lymph node metastases (LNM) of papillary thyroid carcinoma (PTC). Methods A total of 206 patients with PTC subjected to curative surgery were enrolled. All patients had complete medical records. Serum levels of TSGF were detected using Automatic Biochemistry Analyzer and the serum sIL-2R concentration was detected by enzyme-linked immunosorbent assay (ELISA). Furthermore, we analyzed the relationship between the two indicators and the clinicopathological characteristics and assessed their effect on lymphatic metastasis in patients with PTC by logistic regression analysis. Results Receiver operating characteristic (ROC) analysis revealed that the determined cut-off value of serum TSGF and sIL-2R was 63.35 U/mL and 507 U/mL, respectively. Serum TSGF was associated with focality (χ2 = 4.97, P = 0.026) and lymphatic metastasis (χ2 = 4.154, P = 0.042), while serum sIL-2R was remarkably related to gender (χ2 = 4.464, P = 0.035). Univariate logistic regression analysis indicated that age, tumor size, serum TSGF level, capsule invasion, and nodular goiter were the lymphatic metastasis-related factor of PTC. Multivariate regression analysis revealed that age > 45 years was a protective factor (OR: 0.4, 95% CI: 0.206-0.777, P = 0.007). Conversely, larger tumor size (OR: 4.594, 95% CI: 2.127-9.921, P = 0.000), higher serum TSGF levels (OR: 1.888, 95% CI: 1.009-3.533, P = 0.047), and capsule invasion (OR: 1.939, 95% CI: 1.009-3.726, P = 0.047) were associated with an increased risk of LNM. Conclusion Serum TSGF levels were identified as an independent factor for LNM in patients with PTC.

Hyperglycemia is associated with adverse prognosis in patients with pancreatic neuroendocrine neoplasms.

Although glucose has a well-recognized protumoral role and the pancreas is a critical organ in adjusting glucose metabolism, the clinical value of hyperglycemia in pancreatic neuroendocrine neoplasms (pNENs) remains largely unidentified. A retrospective study including 335 patients with pathologically confirmed pNENs was conducted. A baseline fasting blood glucose concentration ≥5.6 mmol/L was defined as hyperglycemia (otherwise, normal). Survival and regression analyses were performed. Compared with patients with normal glucose, patients with hyperglycemia (47.8%) had a higher proportion of preexisting diabetes mellitus (DM) (36.9% vs. 4.6%, p < 0.001), lymph node involvement (31.0% vs. 14.6%, p = 0.002), distant metastasis (34.4% vs. 22.9%, p = 0.019), and carbohydrate antigen 19-9 (CA19-9) ≥ 37 U/mL (16.6% vs. 7.2%, p = 0.009). Hyperglycemia was associated with CA19-9 ≥ 37 U/mL (Odds Ratio (OR) = 3.19, 95% CI: 1.11-9.17, p = 0.031), lymph node involvement (OR = 2.32, 95% CI: 1.02-5.28, p = 0.045), nonfunctional tumors (OR = 9.90, 95% CI: 2.11-46.34, p = 0.004), and preexisting diabetes (OR = 18.24, 95% CI: 4.06-81.95, p < 0.001). Hyperglycemia was an independent determinant for overall survival in the multivariate analysis (hazard ratio (HR) = 2.65, 95% CI: 1.31-5.34, p = 0.006). Hyperglycemia is an independent predictor of overall survival and is associated with preexisting DM or lymphatic metastasis in patients with pNENs. Patients with hyperglycemia and resectable pNENs may benefit from radical resection with dissection of regional lymph nodes.

A Visualized Dynamic Prediction Model for Lymphatic Metastasis in Ewing's Sarcoma for Smart Medical Services.

BackgroundThis study aims to predict the lymphatic metastasis in Ewing's sarcoma (ES) patients by nomogram. The risk of lymphatic metastasis in patients with ES was predicted by the built model, which provided guidance for the clinical diagnosis and treatment planning.MethodsA total of 929 patients diagnosed with ES were enrolled from the year of 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. The nomogram was established to determine predictive factors of lymphatic metastasis according to univariate and multivariate logistic regression analysis. The validation of the model performed using multicenter data (n = 51). Receiver operating characteristics (ROC) curves and calibration plots were used to evaluate the prediction accuracy of the nomogram. Decision curve analysis (DCA) was implemented to illustrate the practicability of the nomogram clinical application. Based on the nomogram, we established a web calculator to visualize the risk of lymphatic metastases. We further plotted Kaplan-Meier overall survival (OS) curves to compare the survival time of patients with and without lymphatic metastasis.ResultsIn this study, the nomogram was established based on six significant factors (survival time, race, T stage, M stage, surgery, and lung metastasis), which were identified for lymphatic metastasis in ES patients. The model showed significant diagnostic accuracy with the value of the area under the curve (AUC) was 0.743 (95%CI: 0.714–0.771) for SEER internal validation and 0.763 (95%CI: 0.623–0.871) for multicenter data external validation. The calibration plot and DCA indicated that the model had vital clinical application value.ConclusionIn this study, we constructed and developed a nomogram with risk factors to predict lymphatic metastasis in ES patients and validated accuracy of itself. We found T stage (Tx OR = 2.540, 95%CI = 1.433–4.503, P < 0.01), M stage (M1, OR = 2.061, 95%CI = 1.189–3.573, P < 0.05) and survival time (OR = 0.982, 95%CI = 0.972–0.992, P < 0.001) were important independent factors for lymphatic metastasis in ES patients. Furthermore, survival time in patients with lymphatic metastasis or unclear situation (P < 0.0001) was significantly lower. It can help clinicians make better decisions to provide more accurate prognosis and treatment for ES patients.

A Novel Nomogram for Prediction and Evaluation of Lymphatic Metastasis in Patients With Renal Cell Carcinoma.

BackgroundLymphatic metastasis is an important mechanism of renal cell carcinoma (RCC) dissemination and is an indicator of poor prognosis. Therefore, we aimed to identify predictors of lymphatic metastases (LMs) in RCC patients and to develop a new nomogram to assess the risk of LMs.MethodsThis study included patients with RCC from 2010 to 2018 in the Surveillance, Epidemiology, and Final Results (SEER) database into the training cohort and included the RCC patients diagnosed during the same period in the Second Affiliated Hospital of Dalian Medical University into the validation cohort. Univariate and multivariate logistic regression analysis were performed to identify risk factors for LM, constructing a nomogram. The receiver operating characteristic (ROC) curves were generated to assess the nomogram’s performance, and the concordance index (C-index), area under curve value (AUC), and calibration plots were used to evaluate the discrimination and calibration of the nomogram. The nomogram’s clinical performance was evaluated by decision curve analysis (DCA), probability density function (PDF) and clinical utility curve (CUC). Furthermore, Kaplan-Meier curves were performed in the training and the validation cohort to evaluate the survival risk of the patients with lymphatic metastasis or not. Additionally, on the basis of the constructed nomogram, we obtained a convenient and intuitive network calculator.ResultsA total of 41837 patients were included for analysis, including 41,018 in the training group and 819 in the validation group. Eleven risk factors were considered as predictor variables in the nomogram. The nomogram displayed excellent discrimination power, with AUC both reached 0.916 in the training group (95% confidence interval (CI) 0.913 to 0.918) and the validation group (95% CI 0.895 to 0.934). The calibration curves presented that the nomogram-based prediction had good consistency with practical application. Moreover, Kaplan-Meier curves analysis showed that RCC patients with LMs had worse survival outcomes compared with patients without LMs.ConclusionsThe nomogram and web calculator (https://liwenle0910.shinyapps.io/DynNomapp/) may be a useful tool to quantify the risk of LMs in patients with RCC, which may provide guidance for clinicians, such as identifying high-risk patients, performing surgery, and establishing personalized treatment as soon as possible.

Frequency of Pelvic Lymphatic Metastases in Patients with Cervical Cancer – A Retrospective Study

Abstract Introduction and objective: The aim of this study was to determine the incidence of pelvic lymph metastases in cervical cancer, depending on the biology of the tumor and the new changes in the staging. Material and methods: A retrospective database analysis involving 85 patients with cervical carcinoma for a 5-year period was performed. Various factors were analyzed for the purpose of the study. Results: In 20% of our patients lymph metastases were found with more frequent locus in the right lymph chains. The average number of metastases was equal to or greater than 2. Moderately differentiated cervical carcinomas metastasized most commonly. The most frequent were metastases in squamous cell carcinoma and in Stage 2B under the TNM classification. After changes in FIGO’s classification the presence of positive lymph nodes defined the disease as III stage. Conclusion: Our study confirms that cervical carcinoma metastasizes in the pelvic lymph nodes before it reaches the para-aortic lymph nodes.

Value of HMGB1 expression for assessing gastric cancer severity: a systematic meta-analysis.

ObjectiveTo evaluate the clinical value of high mobility group box-1 (HMGB1) expression levels in patients with gastric cancer.MethodsArticles published from January 2000 to August 2022 were searched using PubMed, Google Scholar and Science Direct, Springer, Wiley and NIH to evaluate the clinicopathological significance of HMGB1 expression in gastric cancer.ResultsA total of 156 publications were selected, of which six studies, comprising 846 patients, met the criteria for inclusion in this study. Forest plots of clinicopathological characteristics indicated that HMGB1 expression was not associated with age (odds ratio (OR) = 1.07, 95% confidence interval (CI): 0.89–1.28), sex (OR = 0.90, 95% CI: 0.81–1.00), TNM (OR = 1.39, 95% CI: 0.82–2.37), N stage (OR = 1.42, 95% CI: 0.97–2.07), or tumor differentiation (OR = 0.96, 95% CI: 0.71–1.29), but was highly correlated with pT stage (OR = 1.56, 95% CI: 1.17–2.07). Funnel plots showed no significant publication bias in the included studies in terms of age, sex, TNM, pT stage, N stage, or tumor differentiation.ConclusionHMGB1 expression was significantly correlated with tumor pT stage, but not with age, sex, TNM stage, tumor N stage, tumor differentiation, or lymphatic metastasis in patients with GC.

Platelet Count is Associated with the Rate of Lymph Node Metastasis in Lung Adenocarcinoma.

PurposeEmerging studies have revealed that platelets are involved in tumor metastasis in lung adenocarcinoma (ADC). The solid pathological subtype of lung ADC is associated with metastasis, recurrence, and poor prognosis. However, there is no study exploring the relationship between platelets and different lung pathological subtypes.Patients and MethodsThe association between platelet counts and lymph node metastasis was analyzed in 852 patients with lung ADC who underwent surgery and lymph node dissection. Multivariate logistic analysis was conducted to identify the risk factors of lymph node metastasis. Then, lymph node metastasis and other factors were analyzed to determine their correlation with platelet count and histological subtype.ResultsWe found that the platelet count was associated with lymph node metastasis (P = 0.01) in multivariable analysis, independent of tumor size, predominant subtype, visceral pleural invasion, and microvessel invasion. In patients with a platelet count ≥300 × 109/L, the rate of lymph node metastasis was 38.5%, almost twice as high as that in patients with a platelet count <300 × 109/L (23.2%). Additionally, elevated platelet counts, even those within the normal range, were significantly associated with a higher rate of lymph node metastasis. The mean platelet count in patients with solid-predominant histology (269.70 ± 69.38 × 109/L) was significantly higher than that in patients with other histologies (P < 0.001).ConclusionElevated platelet counts are significantly associated with a higher rate of lymph node metastasis, even if the platelet counts are within the reference range. Platelet counts were significantly higher in patients with solid-predominant histology than in patients with other histologies. In addition, VEGF-C may play an important role in lymphatic metastasis in patients with lung ADC. We hypothesize that antiplatelet therapy may reduce lymph node metastasis in lung ADC patients.

Gene sequencing and expression of Raf-1 in lymphatic metastasis of hypopharyngeal carcinoma.

We performed differential gene screening for lymphatic metastasis of hypopharyngeal carcinoma by gene sequencing. We also aimed to investigate the expression and clinicopathological significance of the screened gene in hypopharyngeal carcinoma lymphatic metastasis. The clinicopathological characteristics of 98 patients with hypopharyngeal carcinoma were collected to make survival analysis by Kaplan-Meier & log-rank test. Six cases of tumor tissues from patients with or without lymphatic metastasis were used for gene sequencing of differentially expressed genes. The most frequently differently expressed genes were validated by RT-PCR and Western blot in another 20 patients diagnosed for hypopharyngeal carcinoma. A total of 70 cases of hypopharyngeal carcinoma tumor tissues and normal tissues were investigated to examine the immunohistochemical expression and to explore the prognostic value by Kaplan-Meier & log-rank test and Cox's test. Lymphatic metastasis has been proved to cause a reduction in postoperative survival of patients with hypopharyngeal carcinoma. The results of gene sequencing analysis showed that Raf-1 was a differentially expressed gene in lymphatic metastasis of hypopharyngeal carcinoma. Moreover, the expression of Raf-1 was significantly up-regulated in tumor tissues of lymphatic metastasis patients compared to non-lymphatic metastasis tumor tissues and normal tissues. Meanwhile, Raf-1 had been verified to be an independent risk factor affecting the prognosis of hypopharyngeal carcinoma. For the first time, we investigated Raf-1 as an independent prognostic risk factor of lymphatic metastasis in hypopharyngeal carcinoma. It suggests that Raf-1 may serve as an important potential biomarker in preventing and diagnosing lymphatic metastasis in patients with hypopharyngeal carcinoma and improving the prognosis of patients.

Clinical study of serum IGFBP7 in predicting lymphatic metastasis in patients with lung adenocarcinoma

PurposeTo find serum tumor markers for predicting the presence of lymphatic metastasis in patients with lung adenocarcinoma, and to explore the diagnostic value of IGFBP7 in predicting if lymphatic metastasis occurs in lung adenocarcinoma. MethodsThe concentration of IGFBP7 in the peripheral blood of 90 serum samples, including 30 patients with lung adenocarcinoma in situ, 30 patients with lung adenocarcinoma metastasis, and 30 normal controls were detected by ELISA. The data were analyzed statistically. ResultsThe concentration of IGFBP7 and D-dimer in the metastatic lung adenocarcinoma group was significantly higher than that in the lung adenocarcinoma in situ group (P < 0.05). The expression level of IGFBP7 in serum of patients with lung adenocarcinoma was associated with the clinical stage (P < 0.05) and lymphatic metastasis (P < 0.05). Using the receiver operating characteristic (ROC) curve, the area under the ROC curve of IGFBP7 was 0.901 (95% Confidence Interval was 0.806 to 0.996), and 0.5 was outside the 95% confidence interval (P < 0.05). The difference was statistically significant. ConclusionsIGFBP7 can predict if the lung adenocarcinoma has lymphatic metastasis, which is helpful to improve the treatment of lung adenocarcinoma, and can be used as a new tumor marker to predict whether the lung adenocarcinoma has lymphatic metastasis or not.

X-linked inhibitor of apoptosis protein accelerates migration by inducing epithelial\u2013mesenchymal transition through TGF-\u03b2 signaling pathway in esophageal cancer cells

BackgroundThe prognosis of esophageal cancer is still dismal because of its high probability of metastasis that is likely related to the cellular process of epithelial–mesenchymal transition (EMT). Recent studies have shown a novel role of X-linked inhibitor of apoptosis protein (XIAP) in regulating the migration process of cancer cells and, therefore, linking to progression and poor prognosis of cancer.MethodsThe expression of XIAP in esophageal squamous cell cancer (ESCC) tissues was determined by immunohistochemistry assay. Cell migration was analyzed by wound healing assay and Transwell assay. The expression of EMT markers (E-cadherin, N-cadherin and Vimentin) was revealed by immunofluorescence assay. Quantitative real‑time PCR analysis and Western blot analysis were used to detect the expression of XIAP and EMT markers as well as transforming growth factor-β (TGF-β) at mRNA and protein level, respectively.ResultsWe found that the expression of XIAP closely correlated to the probability of lymphatic metastasis in patients and that ESCC patients with the high XIAP expression were associated with worse overall survival (OS). Univariate and multivariate analysis also revealed XIAP as an independent prognostic factor for overall survival in ESCC patients. In both EC9706 and TE13 cell lines, knockdown of XIAP decreased the migration of cancer cells by inhibiting EMT process through regulating the TGF-β signaling pathway, pinpointing a regulatory role of XIAP in migratory process upon TGF-β activation.ConclusionsTaken together, our results suggest XIAP as a important prognostic and regulative factor in ESCC patients. XIAP may promote migration of esophageal cancer cells through the activation of TGF-β mediated EMT.

&lt;p&gt;High Tiam1 expression predicts positive lymphatic metastasis and worse survival in patients with malignant solid tumors: a systematic review and meta-analysis&lt;/p&gt;

BackgroundMany studies have explored the prognostic value of T-cell lymphoma invasion and metastasis inducing factor 1 (Tiam1) and its association with lymphatic metastasis in malignant solid tumors, but the conclusions remain controversial. Therefore, we performed a meta-analysis to systematically assess the prognostic value of Tiam1 expression and its association with lymphatic metastasis in malignant solid tumors.MethodsWe searched eligible studies in PubMed, Web of Science and EMBASE databases (from inception up to October 2018). The combined HR with 95% CI was used to estimate the prognostic value of Tiam1 expression. The correlation between Tiam1 expression and lymphatic metastasis was assessed using the combined odds ratio (OR) with 95% CI.ResultsA total of 17 studies with 2,228 patients with solid tumors were included in this meta-analysis. The overall estimated results showed that high Tiam1 expression was significantly associated with shorter overall survival (HR= 2.08, 95% CI: 1.62–2.68, P<0.01), and disease-free survival (HR = 1.86, 95% CI: 1.49–2.32, P<0.01). Besides, we also found that there was a close relationship between high Tiam1 expression and positive lymphatic metastasis (OR=2.63; 95% CI: 1.79–3.84, P<0.01).ConclusionHigh Tiam1 expression was significantly associated with shorter survival and positive lymphatic metastasis in patients with malignant solid tumors. Therefore, Tiam1 may be a promising prognostic biomarker and an effective therapeutic target for malignant solid tumors.

Risk Factors of Regional Lymph Node Metastasis in Patients with Cervical Cancer.

ObjectivesTo explore the risk factors related to regional lymph node metastasis in cervical cancer and analyze the value of independent risk factors in predicting regional lymph node metastasis.MethodsWe retrospectively analyzed the clinical data of 699 patients who underwent surgery for stage IB1–IIA2 cervical cancer in Quanzhou First Hospital affiliated to Fujian Medical University from 2010 to 2016. The patients were divided into metastasis (n = 92) and non-metastasis (n = 607) groups based on the postoperative pathology of regional lymph node status. The relevant clinicopathological features of the metastasis and non-metastasis groups were compared through variance analysis and chi-square tests. Logistic regression was adopted to screen relevant independent risk factors of regional lymph node metastasis.ResultsIn univariate analysis, International Federation of Gynecology and Obstetrics (FIGO) stages, serum squamous cell carcinoma antigen (SCC-Ag), histological type of squamous carcinoma and maximal tumor diameter were related factors for lymphatic metastasis in patients with cervical cancer. In multivariate analysis, SCC-Ag and histological type of squamous carcinoma were independent prognostic factors for lymphatic metastasis in patients with cervical cancer. Pre-treatment SCC-Ag serum levels, as a predictor of lymph node metastasis of cervical cancer, revealed a sensitivity of 62.07% (95% confidence interval (CI): 51.03–72.62%), specificity of 65.15% (59.07–70.89%), and area under the receiver operating characteristic (ROC) curve of 0.69 (95% CI: 0.61–0.76).ConclusionsCervical cancer patients whose pathological type is squamous carcinoma with high levels of SSC-Ag pre-operation are more likely to be diagnosed with regional lymph node metastasis. Standardized lymph node dissection should be implemented during operation.

OxLDL promotes lymphangiogenesis and lymphatic metastasis in gastric cancer by upregulating VEGF‑C expression and secretion.

Gastric cancer is one of the most malignant tumor types, and its metastasis is a notable cause of mortality. Among the methods of tumor metastasis, lymphatic metastasis is the predominant one in gastric cancer. A previous study reported that the plasma oxidized low-density lipoprotein (oxLDL) is the risk factor associated with the development of tumors in patients with abnormal lipid metabolism, but the influence of plasma oxLDL in the lymphatic metastasis of gastric cancer remains unclear. In the present study, the concentration of plasma oxLDL from patients with gastric cancer was detected with an ELISA kit, and the lymphatic vessel density in gastric cancer tissues was determined by D2-40 staining. The correlation analysis of oxLDL concentration and lymphatic vessel density demonstrated that plasma oxLDL was positively correlated with lymphatic metastasis in patients with gastric cancer. Subsequently, the popliteal lymph node metastasis animal experiment with nude mice confirmed that oxLDL could promote the lymphatic metastasis of gastric cancer. Following this, the western blotting and ELISA data demonstrated that oxLDL promoted the expression and secretion of vascular endothelia growth factor (VEGF)-C in gastric cancer cell lines. Finally, blocking the lectin-like oxLDL-1 (LOX-1) receptor, a specific receptor for oxLDL, and the nuclear factor (NF)-κB signaling pathway following oxLDL (50 µg/ml) treatment in HGC-27 cells revealed that oxLDL could activate the NF-κB signaling pathway mediated by LOX-1, with subsequent upregulation of VEGF-C expression, and secretion in and from gastric cancer cells, and finally that it could promote the lymphatic metastasis of gastric cancer. These data indicate the association between the plasma oxLDL and the lymphatic metastasis of gastric cancer, and indicate that oxLDL elimination may be a potential therapeutic target for the prevention and intervention of early lymph node metastasis in gastric cancer.