Non-lymph Node Metastasis Group Research Articles

Incremental value of PET primary lesion-based radiomics signature to conventional metabolic parameters and traditional risk factors for preoperative prediction of lymph node metastases in gastric cancer.

Precise preoperative prediction of lymph node metastasis (LNM) is crucial for optimal diagnosis and treatment in patients with gastric cancer (GC), in which existing imaging methods have certain limitations. We hypothesized that PET primary lesion-based radiomics signature could provide incremental value to conventional metabolic parameters and traditional risk indicators in predicting LNM in patients with GC. This retrospective study was performed in 127 patients with GC who underwent preoperative PET/CT. Basic clinical data and PET conventional metabolic parameters were collected. Radiomics signature was constructed by the least absolute shrinkage and selection operator algorithm (LASSO) logistic regression. Basedon the postoperative histological results, the patients were divided into LNM group and non-lymph node metastasis (NLNM) group. Receiver-operating characteristic (ROC) was used to evaluate the discriminatory ability of Radiomics score (Rad-score) for predicting LNM and determine whether adding Rad-score to PET conventional metabolic parameters and traditional risk factors could improve the predictive value in LNM. The Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to further confirm the incremental value of Rad-score for predicting LNM in GC. The LNM group had higher Rad-score than NLNM group [(0.35 (-0.13-0.85) vs. -0.61 (-1.92-0.18), P < 0 .001)]. After adjusted for gender, age, BMI, and FBG, multivariable logistic regression analysis illustrated that Rad-score (OR: 6.38, 95% CI: 2.73-14.91, P < 0.0001) was independent risk factors for LNM in GC. Adding PET conventional parameters to traditional risk factors increased the predictive value of LNM in GC (AUC 0.751 vs 0.651, P = 0.02). Additional inclusion of Rad-score to conventional metabolic parameters and traditional risk indicators significantly improved the AUC (0.882 vs 0.751; P = 0.006). Bootstrap resampling (times = 500) was used for internal verification, 95% confidence interval (CI) was 0.802-0.948, with the sensitivity equaled to 89.5%, and positive predictive value (PPV) was 93.5%. When Rad-score was added to conventional metabolic parameters and traditional risk indicators, net reclassification improvement (NRI) was 0.293 (P = 0.0040) and integrated discrimination improvement (IDI) was 0.293 (P = 0.0045). In GC patients, PET Radiomics signature of the primary lesion-based was significantly associated with LNM and could improve the prediction of LNM above PET conventional metabolic parameters and traditional risk factors, which could provide incremental value for individual diagnosis and treatment of GC.

Survival and clinicopathological significance of PYCR1 expression in cancer: A meta-analysis.

BackgroundProline metabolism is closely related to the occurrence and development of cancer. Δ1-Pyrroline-5-carboxylate reductase (PYCR) is the last enzyme in proline biosynthesis. As one of the enzyme types, PYCR1 takes part in the whole process of the growth, invasion, and drug resistance of cancer cells. This study investigated PYCR1 expressions in cancers together with their relationship to clinical prognosis.MethodsA thorough database search was performed in PubMed, EMBASE, and Cochrane Library. RevMan5.3 software was used for the statistical analysis.ResultsEight articles were selected, and 728 cancer patients were enrolled. The cancer types include lung, stomach, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, and renal cell carcinoma. The meta-analysis results showed that the expression of PYCR1 was higher in the clinical stage III–IV group than that in the clinical stage I–II group (OR = 1.67, 95%CI: 1.03–2.71), higher in the lymph node metastasis group than in the non-lymph node metastasis group (OR = 1.57, 95%CI: 1.06–2.33), and higher in the distant metastasis group than in the non-distant metastasis group (OR = 3.46, 95%CI: 1.64–7.29). However, there was no statistical difference in PYCR1 expression between different tumor sizes (OR = 1.50, 95%CI: 0.89–2.53) and degrees of differentiation (OR = 0.82, 95%CI: 0.54–1.24).ConclusionPYCR1 had a high expression in various cancers and was associated with cancer volume and metastasis. The higher the PYCR1 expression was, the poorer the cancer prognosis was. The molecular events and biological processes mediated by PYCR1 might be the underlying mechanisms of metastasis.

Clinical Significance of Detection of Peripheral Blood VASP Level in Lung Cancer Patients.

This paper explores the relationship between the clinical value of vasodilator-stimulated phosphoprotein (VASP) in lung cancer tissue and its diagnosis and severity. Totally 100 patients who were clinically diagnosed with lung cancer from January 2018 to December 2020 were enrolled in our study. They were assigned into two groups according to the presence of lymph node metastasis. The VASP levels were measured by flow cytometry. The correlation between the expression of VASP in tumor tissue and the clinical characteristics and prognosis in patients was analyzed. The diagnostic efficacy of plasma VASP with squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), cytokeratin-19 fragment (CYFRA21-1), prosecretin-releasing peptide (proGRP), and lung cancer was analyzed. The results were compared with APACHE III score to evaluate the accuracy of VASP in determining the severity of patients. This paper finds that the value of VASP in the non-lymph node metastasis group was significantly higher than that in the healthy control group, and the VASP level in the lymph node metastasis group was significantly higher than that in the non-lymph node metastasis group and the healthy control group (all p values <0.05). The APACHE III score of the lymph node metastasis group was higher than that of the non-lymph node metastasis group (p value <0.05). The diagnostic efficacy of VASP is similar to that of SCC, NSE, CYFRA21-1, and proGRP. The plasma VASP value was statistically different in the survival group and the death group, with higher level observed in the death group compared to survival group (all p values <0.05). The value of plasma VASP alone and acute physiology and chronic health evaluations III (APACHE III) score for lung cancer mortality was similar (47.06% vs. 52.94%, p value >0.05). Similar accuracy was observed in VASP and APACHE III score in predicting mortality of lung cancer (84.37% vs. 85.77%, p value>0.05). This paper concludes that the level of VASP correlates to the severity of the lung cancer and survival of the patients.

Diagnostic Value of Serum TSH, Ultrasound, and Enhanced CT in Papillary Thyroid Carcinoma with Lymph Node Metastasis

Objective: To explore the diagnostic value of serum TSH, ultrasound, and enhanced CT in papillary thyroid carcinoma with lymph node metastasis. Methods: 168 patients who underwent thyroidectomy in Shaanxi Provincial People’s Hospital from January 2020 to December 2021 were selected as the research subjects. Based on the pathological nature (benign or malignant), they were divided into two groups, with 86 patients in the control group and 82 patients in the study group. Based on whether the pathology was accompanied with lymph node metastasis, the PTC group was divided into a lymph node metastasis group and a non-lymph node metastasis group, with 51 and 31 patients in the respective groups. Retrospective analysis was conducted to observe and analyze the pathological results of the thyroid nodules’ thyroid ultrasound results, neck enhanced CT results, and thyroid function test serology results. Results: Compared with the PTC group, there were significant differences in TR classification, ultrasonic lymph nodes, and enhanced CT lymph nodes, but no significant differences in the course of disease, nodule distribution, and the number of nodules between the benign nodule group and PTC group; in the comparison of lymph node metastasis using ultrasound and enhanced CT, the number of patients with ultrasound lymph nodes without abnormal metastasis in the non-metastasis group was 28, while that of the metastasis group was 21; the number of patients with abnormal metastasis in the non-metastasis group was 3, while that of the metastasis group was 30. The number of patients with a single node without metastasis and metastasis was 14 and 8, respectively, whereas the number of patients with multiple nodes without metastasis and metastasis was 17 and 43, respectively. There were statistically significant differences in the number of ultrasound lymph nodes and nodules, but no statistically significant differences in TR classification, enhanced CT lymph nodes, nodules distribution, and disease course. Conclusion: Serum TSH can be used to identify the nature (benign and malignant) of thyroid nodules, and enhanced CT is better than ultrasound when evaluating complex lesions. It can be used as a supplement to ultrasound based on clinical context.

Evaluation of the Property of Axillary Lymph Nodes and Analysis of Lymph Node Metastasis Factors in Breast Cancer by Ultrasound Elastography.

This research was aimed at investigating the role of ultrasound elastography (UE) in evaluating the properties of axillary lymph nodes in breast cancer and exploring the influencing factors of lymph node metastasis in breast cancer patients. Routine ultrasonography (US) and UE were performed for 160 breast cancer patients. 80 cases were in the group with lymph node metastasis, and the other 80 were in the nonlymph node metastasis group. The sensitivity, specificity, and accuracy of the two ultrasound examinations were compared, the receiver-operator characteristic (ROC) curves were drawn, and the influencing factors of lymph node metastasis were analyzed. The sensitivity, specificity, and accuracy of UE in diagnosing axillary lymph nodes of breast cancer were 97.22%, 95.45%, and 96.25%, respectively, which were markedly higher than those of routine US (P < 0.05). Cortical thickness, blood flow grade, blood flow type, and elasticity score had a greater impact on axillary lymph node metastasis of breast cancer. When cortical thickness ≥ 3 cm, blood flow was of 2-3 grades, blood flow was the peripheral/mixed type, and elasticity score was 3-4 points, these became risk factors for lymph node metastasis in breast cancer patients. UE was effective in diagnosing the property of lymph nodes and could evaluate lymph node metastasis in breast cancer patients. It had a good clinical value and was worthy of popularization and application.

Molecular profiles and circulating tumor-DNA detected in Chinese early stage breast cancer.

With the development of gene-sequencing technology, genome biomarkers, including Erb-B2 receptor tyrosine kinase 2 (ERBB2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (pIK3CA), BReast CAncer gene 1 (BRCA1), and BReast CAncer gene 2 (BRCA2), and immunomarkers, including the tumor mutational burden (TMB) and programmed death-ligand 1 (PD-L1), have become important in the selection of treatment. Twenty patients with early stage breast cancer who underwent surgery were enrolled in this study. Tissue samples and paired postoperative peripheral blood samples were collected and subjected to the targeted-capture sequencing of 1,021 cancer-associated genes. The most frequently altered genes were tumor protein 53 (TP53; 70%), PIK3CA (40%), protooncogene MYC (35%), ERBB2 (30%), and cyclin-dependent kinase 12 (CDK12; 20%). Six (30%) patients presented with ERBB2 amplification of NGS and simultaneously were positive for human epidermal growth factor receptor 2 (HER2) of IHC. ERBB2 amplification and being HER2 positive were common in breast cancer patients without lymph node metastasis (5/6, 83.3%) and those in stages IA-IIA. Most of the somatic mutations clustered in the TP53 pathway, followed by the PI3K pathway. The TMB was lower than metastatic breast cancer in our cohort, and ranged from 0 to 9.6 mut/Mb (median: 1.92 mut/Mb). Interestingly, more patients had the ERBB2 mutation in the non-lymph node metastasis group than the lymph node metastasis group (55.6% vs. 9.1%; P=0.049). Similarly, more patients had the CDK12 mutation in the non-lymph node metastasis group than the lymph node metastasis group (44.4% vs. 0%; P=0.026). Circulating tumor deoxyribonucleic acid (ctDNA) was detected in 7 of the 20 patients (35%). Of these patients, 71.4% (5/7) were in stage I/II. In addition, no correlation was found between ctDNA detection and clinicopathological features or the driver gene mutations (e.g., PIK3CA and ERBB2). However, patients positive for ctDNA had a higher TMB than those negative for ctDNA when grouped according to the median TMB (1.92 mut/Mb; 85.7% vs. 38.5%; P=0.043). This study described that genomic characteristics of Chinese early stage breast cancer, and the results showed that TMB was related to the detection of ctDNA in postoperative blood.

Application Value of Combined Detection of Serum IGF-I and IGFBP-3 in the Diagnosis of Bladder Cancer

Objective. To investigate the application value of the combined detection of serum IGF-I and IGFBP-3 in the diagnosis of bladder cancer (BC). Methods.Sixty BC patients in our hospital (January 2019-January 2020) were chosen as group A, while sixty healthy people during the same period were chosen as group B. The serum IGF-I and IGFBP-3 levels of the subjects were detected to explore the relationship between the two levels (serum IGF-I and IGFBP-3) and BC.Results.Compared with group B, the two levelsof group A were lower while IGF-l/IGFBP-3 was higher. Compared with low-grade BC group, non-muscle invasive BC (NMIBC) group and non-lymph node metastasis group, the two levels were lower in high-grade BC group, muscle-invasive BC (MIBC) group and lymph node metastasis group (P&lt;0.05). No notable difference in IGF-l/IGFBP-3 was found among patients with high-grade or low-grade BC, with or without lymph node metastasis, andwith or without muscular invasion (P&gt;0.05). Conclusion. The serum IGF-I and IGFBP-3 levels of BC patients are obviously different compared with healthy people, and vary in patients with different types of BC, indicating the two factors can be applied in clinical diagnosic of BC.

MRI associated biomarker analysis for diagnosis of lymph node metastasis in T1-2 stage rectal cancer

Objective: To explore the diagnostic accuracy improved by magnetic resonance imaging (MRI) biomarkers for lymph node metastasis in T1-2 stage rectal cancer before treatment. Methods: Medical records of 327 patients with T1-2 rectal cancer who underwent pretreatment MRI and rectal tumor resection between January 2015 and November 2019 were retrospectively analyzed. Fifty-seven cases were divided into the lymph node metastasis group (N+ group) while other 270 cases in the non-lymph node metastasis group (N-group) according to the pathologic diagnosis. Two radiologist evaluated the tumor characteristics of MRI images. The relationship of the clinical and imaging characteristics of lymph node metastasis was assessed by using univariate analysis and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic abilities for the differentiation of N- from N+ tumors. Results: Among the 327 patients, MR-N evaluation was positive in 67 cases, which was statistically different from the pathological diagnosis (P<0.001). The sensitivity, specificity and accuracy of MRI for lymph node metastasis were 45.6%, 84.8% and 78.0%, respectively. Multivariate regression analysis showed that tumor morphology (P=0.002), including mucus or not (P<0.001), and MR-N evaluation (P<0.001) were independent influencing factors for stage T1-2 rectal cancer with lymph node metastasis. The area under the ROC curve of rectal cancer with lymph node metastasis analyzed by the logistic regression model was 0.786 (95%CI: 0.720~0.852). Conclusions: Tumor morphology, including mucus or not, and MR-N evaluation can serve as independent biomarkers for differentiation of N- and N+ tumors. The model combined with these biomarkers facilitates to improve the diagnostic accuracy of lymph node metastasis in T1-2 rectal cancers by using MRI.

Predictive value of S100A9 for lymph node metastasis in cervical cancer.

Lymph node metastasis affects the initial treatment strategy for cervical cancer and is hard to be diagnosed in clinical practice.This paper aims to explore the relationship between calcium-binding A9 (S100A9) and lymph node metastasis (LNM) in cervical cancer, and to determine the predictive value of S100A9 for LNM in cervical cancer. We performed a retrospective cohort study and collected the pathological data, follow-up data, and paraffin tissue samples of 99 patients with cervical cancer who underwent modified extensive or extensive hysterectomy plus pelvic lymphadenectomy at the Department of Gynecology, Xiangya Hospital, Central South University from January 2013 to December 2018. Immunohistochemistry was used to detect the expression of S100A9 in cervical cancer tissues, and the correlation between S100A9 expression and LNM of cervical cancer, or clinicopathological characteristics were analyzed. The receiver operating characteristic (ROC) curve was used to establish a predictive model for LNM of cervical cancer, and Chi-square test of four-grid table was used to evaluate the diagnostic value of S100A9 for LNM in cervical cancer. The expression of S100A9 was significantly correlated with LNM. The S100A9 immunohistochemical semi-quantitative score of the LNM group was significantly higher than that in the non-lymph node metastasis group (P<0.001). Moreover, the expression of S100A9 was significantly correlated with histological type, stromal invasion, lymphatic vessel invasion, or LNM (P<0.05). The cut-off of the ROC curve for predicting LNM was 5, with the Youden index of 0.649 and the area under the ROC curve of 0.863. The disease-free survival and overall survival in the S100A9 positive group were significantly shorter than those in the negative group (P<0.05). S100A9 alone had a sensitivity of 71.4%, a specificity of 91.5%, and an accuracy of 85.1% for diagnosing LNM. Imaging had a sensitivity of 32.1%, a specificity of 74.6%, and an accuracy of 60.9%. Combination of S100A9 with image examination in parallel test had a sensitivity of 85.7%, a specificity of 71.2%, and an accuracy of 75.9%, while combination of S100A9 and image examination in serial test had a sensitivity of 17.9%, a specificity of 98.3%, and an accuracy of 72.4%. S100A9 may be associated with LNM in cervical cancer. S100A9 shows a promising perspective in predicting LNM in cervical cancer. Combination of S100A9 and image examination in serial test has a high specificity for LNM.

Potential value of FDG PET-CT in predicting occult lymph node metastasis in clinical stage ⅠA lung adenocarcinoma

Objective: To investigate the predictive value of (18)F-FDG PET-CT scan for occult lymph node metastasis in patients with stage ⅠA lung adenocarcinoma. Methods: The image and pathological data of 272 patients with stage ⅠA lung adenocarcinoma from October 2006 to September 2015 were retrospectively analyzed. All patients underwent preoperative (18)F-FDG PET-CT scan followed by lobectomy and systematic lymph node dissection. The correlation between occult lymph node metastasis and the maximum standardized uptake value (SUV(max)) of primary tumor as well as other clinicopathological factors was analyzed to screen the risk factors of occult lymph node metastasis in stage ⅠA lung adenocarcinoma. Results: Occult lymph node metastasis was detected in 50 patients (18.4%), with 24 (8.8%) patients of pN1 involvement and 26 (9.6%) of pN2 involvement. Among the 272 patients enrolled, 39 had pure ground glass nodule, 59 had part-solid nodule and 174 had solid nodule. All patients with pure ground glass nodule or nodule≤1 cm were pN0. For the 233 patients with part-solid and solid nodule, no lymph node metastasis was found in T1a stage (tumor length ≤1 cm). Primary tumor SUV(max) (Z=-5.663, P<0.001), nodule type (χ(2)=21.586, P<0.001), tumor location (χ(2)= 12.790, P< 0.001), histological grade (χ(2)= 22.784, P< 0.001) and visceral pleural invasion (χ(2)=5.357, P=0.021) showed significant differences between occult lymph node metastasis group (pN+ ) and non-lymph node metastasis group (pN0). With SUV(max)=2.405 as cut-off value, the sensitivity and specificity for predicting occult lymph node metastasis were 90.0% and 61.7%, the area under curve was 0.761(95%CI=0.700~0.823), and the negative predictive value was 95.8%. Multivariate analysis revealed that SUV(max) >2.405 (P<0.001), central location (P=0.030) and higher histological grade (P=0.024) were independent predictors of occult lymph node metastasis. Conclusions: For clinical stage ⅠA adenocarcinoma, primary tumor SUV(max) > 2.405, central location and higher histological grade were independent risk factors for occult lymph node metastasis. Systematic lymph node dissection may be avoided in lung adenocarcinoma with pure ground glass density, tumor length ≤1 cm or SUV(max) ≤ 2.405, due to the very low probability of nodal involvement.

TUSC3 as a potential biomarker for prognosis in clear cell renal cell carcinoma.

The aim of the present study was to explore the expression levels of tumor suppressor candidate 3 (TUSC3) in human clear cell renal cell carcinoma (ccRCC) and its clinical value. Immunohistochemical staining, western blotting and reverse transcription-quantitative polymerase chain reaction were used to detect TUSC3 expression in paracancerous normal tissues and ccRCC tissues. The tissues were derived from the pathological specimens of 54 patients with ccRCC. Additionally, associations among TUSC3 expression and histological grade and clinicopathological staging of ccRCC were investigated. The results of these comparisons revealed that TUSC3 expression in ccRCC tissues was significantly lower than that in paracancerous tissues (P<0.05). TUSC3 expression in the high differentiation group was higher than that in the median and low differentiation groups (P<0.05). Expression levels of TUSC3 in stage I and II tissues were higher than those in stage III and IV tissues (P<0.05). The expression levels of TUSC3 in the lymph node metastasis group were lower than those in the non-lymph node metastasis group (P<0.05). In conclusion, the expression levels of TUSC3 in human ccRCC tissues were downregulated compared with those found in normal human renal tissue, and TUSC3 may inhibit the progression of ccRCC. Furthermore, the TUSC3 gene may be used as a promising tumor marker for the early diagnosis and prognosis of ccRCC.

The correlation between TNF-α-308 gene polymorphism and susceptibility to cervical cancer

Tumor necrosis factor-α (TNF-α) is closely related to the occurrence of human cancers. Cervical cancer seriously affects female health. Therefore, our study aimed to investigate the correlation between the polymorphism of TNF-α-308 gene and susceptibility to cervical cancer. Whole blood was collected from 142 patients with cervical cancer and 150 healthy controls. PCR-RFLP was used to detect the polymorphism of TNF-α-308 and the correlation between polymorphism of TNF-α-308 and the susceptibility to cervical cancer was analyzed. The three genotypes of TNF-α-308 were GG, GA and AA, and the distributions of genotypes of TNF-α-308 were consistent with Hardy-Weinberg equilibrium in both cervical cancer group and control group. There were no significant differences in genotype and allele frequency between cervical cancer group and healthy control group (P>0.05). A/A genotype increased the risk of cervical cancer by 1.46 times with 95% confidence interval of 0.32–6.67. Different genotypes were not associated with tumor type (P>0.05). Different genotypes are correlated with cervical cancer TNM stages, tumor differentiation and lymph node metastasis. Proportion of GA+AA genotype in TNM stage III+IV group, low differentiation group and lymph node metastasis group were 28.1, 29.0 and 29.8%, respectively, which were significantly higher than those in stage I+II group, moderate/high differentiation group and non-lymph node metastasis group (P<0.05). The results suggested that TNF-α-308 gene polymorphism is associated with the degree of malignancy of cervical cancer. Female patients with A allele have higher malignant degree of cervical cancer.

Clinicopathological analysis of lymph node metastasis in colorectal adenocarcinoma

To analyze the correlation of lymph node metastasis with clinicopathological parameters and outcomes of colorectal adenocarcinoma, and to explore its clinicopathological significance. The lymph node metastasis and clinicopathological features of 133 colorectal adenocarcinoma patients whose specimens were interpreted in Department of Pathology of Beijing Tongren Hospital between February 2011 and August 2015 were retrospectively analyzed. The relationship between the lymph node metastasis and clinicopathological features as well as outcomes was also analyzed according to the follow-up data of these patients. Among the 133 cases, 69 had lymph node metastasis, and the other 64 had no lymph node metastasis. Compared with the non-lymph node metastasis group, the lymph node metastasis group had higher prevalence of neural invasion (20.29% vs 3.13%) and vascular invasion (36.23% vs 3.13%), deeper tumor invasion (beyond the serosa: 1.45% vs 0), lower tumor differentiation (poorly differentiated: 26.09% vs 14.06%), higher mortality (11.59% vs 1.56%) and distant metastasis (17.39% vs 4.69%) (all P<0.05). In the lymph node metastasis group, intra-group comparison among patients of different lymph node N staging (N0, N1a, N1b, N2a, N2b) also showed statistically significant differences in neural invasion, vascular invasion, circumferential resection margin, maximum diameter of the tumor, depth of tumor invasion, tumor differentiation, survival, and distant metastasis (all P<0.05). There were no statistically significant differences between the patients with lymph node metastases <12 and those with lymph node metastases ≥12 in these clinicopathological parameters(all P>0.05). Presence/absence of lymph node metastasis and lymph node stage may be correlated with neural invasion, vascular invasion, depth of tumor invasion, tumor differentiation, survival, and distant metastasis. However, no marked relationship was detected of the number of lymph node metastases (<12 or ≥12) with clinicopathological parameters and outcomes.

The NHERF3 expresssion in renal cell carcinoma and its clinical significance

Objectives To investigate the NHERF3 expresssion in renal cell carcinoma and its clinical significance. Methods 58 cases of renal cell carcinoma patients and 40 cases of non-renal cell carcinoma (control group) were enrolled in this study. The expression of NHERF3 were measured by immunohistochemistry. Results The positive expression rate of NHERF3 in renal cell carcinoma was 53.45% (31/58), which was significantly higher than that in control group 17.50% (7/40) (P 0.05). The positive expression rate of NHERF3 in Ⅰ and Ⅱ stage was 41.94%(13/31), which was lower than that of 66.67%(18/27)in Ⅲ and Ⅳ stage (P<0.05). The positive expression rate of NHERF3 in well differentiation group was 35.71%(10/28), which was lower than that of 70.00%(21/30)in low differentiation group(P<0.05). The positive expression rate of NHERF3 in non-lymph node metastasis group was 27.27%(6/22), which was lower than that of 69.44%(25/36)in lymph node metastasis group(P<0.05). Conclusions The positive expression of NHERF3 is closely related to the metastasis, differentiation and prognosis of renal cell carcinoma, and which may become a potential marks for clinical classification, prognosis evaluation and drug therapy. Key words: Kidney Neoplasms; Oncogenes

The experimental study of B cell lymphoma/leukemia-2 and twist family basic helix-loop-helix transcription factor 1 expression in oral squamous cell carcinoma and role of modulating epithelial-mesenchymal transition

Objective To sutdy the expression of B cell lymphoma/leukemia-2 (bcl-2), twist family basic helix-loop-helix transcription factor 1 (Twist1) in oral squamous cell carcinoma and its modulating epithelial-mesenchymal transition (EMT). Methods Immunohistochemistry was used to detect the bcl-2, Twist1 and EMT related proteins expression among 82 OSCC samples and 24 paracancerous samples. The relationship between the bcl-2, Twist1 and the EMT biomarkers was analyzed. Western blotting were used to observe the bcl-2, Twist1 and EMT related proteins expression. Immunoprecipitation were used to assessed interaction between bcl-2 and Twist1. Results bcl-2, Twist1 expression in oral squamous cell carcinoma was significantly higher than the adjacent tissues. Of 82 cases OSCC, bcl-2 overexpression were found in 48 cases (58.64%) and Twist1 overexpraeeion were in 46 cases (56.10%), which were significantly higher than the adjacent tissues [bcl-2: 6 cases (25.00%), P<0.05, Twist1: 4 cases (16.67%), P<0.05]. In poorly differentiated and lymph node metastasis group, the expression of bcl-2, Twist1, N-cadherin, Vimentin were higher than those in high differentiation and non-lymph node metastasis group. Twist1 showed a positive correlation with bcl-2, N-cadherin, Vimentin (correlation coefficients were 0.303, 0.249, 0.348 respectively, P<0.05), but negatively correlated with E-cadherin (correlation coefficient of -0.547, P<0.05). Immunoprecipitation showed that bcl-2, Twist1 can interact with each other. Conclusion bcl-2 and Twist1 overexpressed in oral squamous cell carcinoma and form a complex, bcl-2/Twist1 complex might play a critical role in modulating EMT. Key words: Oral squamous cell carcinoma; B cell lymphoma/leukemia-2; Twist family basic helix-loop-helix transcription factor 1; Epithelial-mesenehymal transition; Lymthatic metastasis

The experimental study of CXC subfamily receptor 4 modulating oral squamous cell carcinoma epithelial-mesenchymal transition to influence lymphatic metastasis in vitro

To sutdy the effect and mechanism of CXC chemokine receptor 4 (CXCR-4 )modulating oral squanmous cell carcinoma (OSCC) epithelial-mesenchymal transition (EMT)to mediate tumor lymphatic metastasis. Immunohistochemistry was used to detect the CXCR-4 and EMT related proteins among 60 OSCC samples with different lymph node metastasis status and the relationship with clinicopathological features and EMT related factors were analyzed. The small interfering RNA (siRNA) was applied to silence CXCR-4 in Tscca cell.Reverse transcription-PCR and Western blotting were used to observe the inhibitory effect. The wound healing assay, transwell invasion assay and flow cotometry were used to detect Tscca cell migration, invasion ability and apoptosis. In lymph node metastasis group, the expression of CXCR-4, N-cadherin, Twist, Snail were higher than those in non-lymph node metastasis group. CXCR-4 showed a positive correlation with Twist, Snail, N-cadherin (correlation coefficient:0.300, 0.256, 0.333, P < 0.05), but negatively correlated with β-catenin (correlation coefficient:-0.497, P < 0.05). CXCR-4 silencing inhibited the migration and invasion of Tscca cell and induced apoptosis of the cell. Western blotting results indicated that N-cadherin, matrix metalloproteina-2/9 (MMP-2/9) was decreased (N-cadherin: F = 20.999, P = 0.002; MMP-2: F = 47.156, P = 0.000; MMP-9: F = 142.317, P = 0.000) while E-cadherin was up-regulated (F = 111.022, P = 0.000). CXCR-4 might play a critical role in the metastasis of OSCC via modulating EMT.

Expression of vascular endothelial growth factor C in esophageal carcinoma and its clinical significance

Objective To investigate the expression of vascular endothelial growth factor C (VEGF-C) in human esophageal squamous cell carcinoma (ESCC) and its clinical significance.Methods The expression of VEGF-C in ESCC and its correlation with lymph node metastasis were detected by using immunohistochemistry (IHC) and in situ hybridization (ISH).Three small interfering RNA (siRNA) expression vectors targeting VEGF-C were constructed and transformed into EC9706 cells.The inhibitory effect of siRNA on the expression of VEGF-C protein and mRNA in tranfected cells was analyzed by using Western blotting and reverse transcription-polymerase chain reaction (RT-PCR).Stably transfected cells were transplanted in nude mice later.The expression of VEGF-C in transplant tumor was detected by using IHC and ISH.Results VEGF-C was up-expressed in ESCC.Its expression was correlated significantly with lymph node metastasis.The positive expression rate of VEGF-C in lymph node metastasis group and non-lymph node metastasis group was 90.0％ and 62.1％ respectively (P ＜0.01 ).VEGF-C-targeted siRNA could decrease the expression of VEGF-C mRNA and protein in EC9706 cells effectively.There was significant difference between transfected group (0.32 ± 0.02) and un-transfected group (0.91 ± 0.09,P ＜0.01 ).Correspondingly,the expression of VEGF-C was 9.26 ±0.95,8.94 ±0.81,9.19 ±0.92 and 32.47 ±3.25 respectively.There was significant difference among them (P ＜0.01 ).Conclusion Targeting VEGF-C siRNA can inhibit VEGF-C expression of EC9706 in vivo and in vitro effectively. Key words: Esophageal neoplasm; Vascular endothelial growth factor C

Expression and clinical significance of bromodomain-containing protein 7 in non-small cell lung cancer

背景与目的溴区包含蛋白7（bromodomain-containing protein 7, BRD7）基因属于bromodomain家族成员，该家族的大多数成员与上皮类肿瘤的发生密切相关。本研究旨在探讨BRD7在非小细胞肺癌（non-small cell lung cancer, NSCLC）中的表达及其临床意义。方法采用免疫组化法检测101例NSCLC癌组织及其33例正常肺组织中BRD7的表达情况。结果BRD7在NSCLC组织中的阳性表达率明显高于正常肺组织；BRD7在淋巴结转移组阳性表达率高于无淋巴结转移组；BRD7的阳性表达率随着TNM分期的升高而升高。BRD7的阳性表达与患者年龄、性别、吸烟情况、病理类型、分化程度无关（P>0.05）。结论BRD7在NSCLC中有较高的表达率，除了与淋巴结转移有关外，还与TNM分期有关，提示BRD7可能与肺癌的发生、发展和转移有关。

Association between lymphangiogenesis and clinicopathological features and prognosis in laryngeal carcinoma

To detect lymphangiogenesis by labeling the lymphatic endothelial marker, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), and study the prognostic relevance of lymphangiogenesis in laryngeal squamous carcinoma. Clinical files and specimens of 78 patients with histologically diagnosed laryngeal carcinoma were stained with LYVE-1 as a specific lymphatic endothelial marker. The lymphatic vessel density (LVD) was measured, and the correlation between LVD and clinicopathological features of the tumor cases was analyzed. The mean LVD in laryngeal carcinoma (13.24 ± 5.09) was significantly higher than that in adult laryngeal papilloma (5.54 ± 3.15) and squamous dysplasia (6.76 ± 4.45, P < 0.05). The LVD of poorly differentiated tumors (15.74 ± 5.24) was significantly higher than that in the moderately differentiated tumors (13.84 ± 6.20), and the LVD in the moderately differentiated tumors was significantly higher than that in the well-differentiated tumors (11.68 ± 6.34). The LVD in stage 0 to stage II group (10.66 ± 5.70) was significantly lower than that in the stage III to IV group (17.01 ± 6.35). The lymph node metastasis group (17.25 ± 7.37) was significantly higher than non-lymph node metastasis group (8.60 ± 5.23, P < 0.05). There was no significant association between LVD and age, sex, primary site and distant metastasis. The overall survival in the patients with a LVD higher than the mean value was 33.5 month, and that of cases with a LVD lower than the mean value was 81.6 month (P < 0.05). The multivariate survival analysis showed that the clinical stage and LVD were independent prognostic factors of laryngeal cancer. The LYVE-1 staining histochemistry demonstrates that the lymphangiogenesis occurrs mainly at the edge of the tumors, and lymphangiogenesis plays an important role in the carcinogenesis, cancer progression and lymph node metastasis in laryngeal cancer. LVD may be an independent indicator of poor prognosis of laryngeal cancer.

Expression and clinical significance of adhesion molecule CD11c in gastric carcinoma

Objectiye To investigate the expression of CD11c in gastric carcinoma and the clinical significance. Methods The expression of CD11 c in gastric carcinoma, gastritis tissue and gastric polyp was detected by using immunohistochemical assay. Results The expression level of CD11c in gastric carcinoma was higher than that in gastritis tissue and gastric polyp. There was no significant difference in the CD11 c expression among gender, age, pathological grade, primary area (P ＞ 0. 05 ). There was significant difference in the CD11c expression among tumor size, invasive depth, lymph node metastasis, histological type, recurrence and clinical stage. The expression of CD11c in tumor size ＜5 cm group ( 12.4 ±6. 8 ) was higher than that in tumor size ≥ 5 cm group (7.7 ± 4. 6), ( t = 3.98, P ＜ 0. 01 ). The expression of CD11c in non-invasion group ( 15.4 ± 8.5 ) was obviously higher than that in invasion group (9.5 ±5.6), ( t = 3.1 ,P ＜ 0. 05 ). The expression of CD11c in non-lymph node metastasis group ( 15.3 ± 6. 6 )was obviously higher than that in lymph node metastasis group ( 8. 6 ± 5. 1 ), ( t = 5. 44, P ＜ 0. 01 ). The expression of CD11c in non-recurrence group ( 12.3 ±7.4) was higher than that in recurrence group (9. 0± 5.3), ( t= 2.90, P ＜ 0. 01 ). The expression of CD11 c in differentiation group ( 9. 3 ± 5.3 ) was lower than that in low differentiation group ( 12. 6 ± 7. 8 ), ( t = 2. 68, P ＜ 0. 01 ). There was significant diference among groups of clinical stage (P ＜0. 01 ). The multivariate Cox analysis revealed that the risk of death in high expression group was significantly lower than that in low expression group (RR =0. 51, 95% CI=0. 22-1.16). Conclusion Detection of the CD11c expression in gastric carcinoma is beneficial to the judgment of the prognosis of gastric carcinoma and the choice of individualized treatment. Key words: Gastric carcinoma; CD11 c; Adhesion molecules; Immunohistochemical