Purpose To investigate the correlation between molecular typing of urothelial carcinoma(UC)and its clinicopathologic features and prognosis,in order to explore the prognostic markers and therapeutic targets for UC.Methods 115 patients with UC were retrospectively analyzed.Immunohistochemical markers GATA-3,CK20,CK5/6 and CD44 were used for molecular typing of UC(luminal-like type,basal-like type and null).Correlations between molecular typing and clinicopathological features were analyzed using the Chi-square test and Fisher precise test.Sur-vival analysis was performed using the Kaplan-Meier test and Log-rank test.Results The expression of GATA-3 and CK20 was negatively correlated with the clinical stage of UC,while the expression of CD44 was positively correlated with the clinical stage of UC(both P＜0.05).CK20 was a marker of good prognosis(P=0.03).The proportion of clinically advanced UC with basal-like type was significantly higher than that of luminal-like type(78.4％vs 53.4％,P=0.033).Among the histologic variants,UC with neuroendocrine differentiation(100％),sarcomatoid carcinoma(80.0％)and squamous differentiation(77.8％)were basal-like type.All plasmacytoid and lymphoepithelioma-like types,as well as 81.8％of micropapillary UC.Among the null phenotypes,the differential variant predominated(66.7％).Compared with the luminal-like type,although the prognosis of basal-like UC was worse,there was no sta-tistically significant difference(P＞0.05).Conclusion Patients with CK20-expressing UC had a significantly better prognosis.The main histologic variants types of basal-like type and coelomofacial type are different.Molecular typing of UC using immunohistochemical markers is suggestive of clinical staging and prognosis of patients.

Purpose To investigate the relationship between the expression of POSTN and NECTIN-3 in urothelial carcinoma(UC)and its clinicopathologic features and prognosis.Methods Clinical data of 115 UC patients were col-lected.EnVision two-step method was used for immunohistochemical analysis to determine the expression of POSTN and NECTIN-3 in UC and their correlation with clinicopathological features and prognosis.Transcriptomic data from TCGA database were used to analyze the correlation between the expression of POSTN and NECTIN-3 in bladder cancer and the pathological stage and prognosis of bladder cancer.qPCR and Western blot were used to detect the expression levels of POSTN and NECTIN-3 in tumor tissues and adjacent tissues of patients.Results TCGA database analysis showed that the expression level of NECTIN-3 in urinary bladder urothelial carcinoma(UBUC)was significantly lower than that in paracancer tissues,and POSTN expression was positively correlated with pathological stage.Prognostic a-nalysis showed that POSTN expression was negatively correlated with the overall survival of UBUC(P＞0.05),and NECTIN-3 expression was negatively correlated with disease-free survival of UBUC(P＞0.05).The experimental re-suits showed that patients with positive POSTN expression were more prone to perineural invasion[25 cases(86.2％)vs 4 cases(13.8％),P=0.019],vascular invasion[36 cases(83.7％)vs 7 cases(16.3％),P=0.007],and lymph node metastasis[24 cases(88.9％)vs 3 cases(11.1％),P=0.033].Additionally,the positive expression rate of POSTN in UBUC was significantly higher than that in upper tract urothelial carcinoma(UTUC)(75.0％vs 54.3％,P=0.028).Higher expression levels of POSTN and NECTIN-3 were associated with shorter overall survival,but the difference was not statistically significant(P＞0.05).Conclusion There is no significant correlation between NECTIN-3 and the clinicopathological features and prognosis of urothelial carcinoma,while the expression of POSTN is correlated with the invasive clinicopathological features of UC,which has certain suggestive significance for clinical stage and prognosis.

Purpose To investigate the correlation between molecular typing of urothelial carcinoma(UC)and its clinicopathologic features and prognosis,in order to explore the prognostic markers and therapeutic targets for UC.Methods 115 patients with UC were retrospectively analyzed.Immunohistochemical markers GATA-3,CK20,CK5/6 and CD44 were used for molecular typing of UC(luminal-like type,basal-like type and null).Correlations between molecular typing and clinicopathological features were analyzed using the Chi-square test and Fisher precise test.Sur-vival analysis was performed using the Kaplan-Meier test and Log-rank test.Results The expression of GATA-3 and CK20 was negatively correlated with the clinical stage of UC,while the expression of CD44 was positively correlated with the clinical stage of UC(both P＜0.05).CK20 was a marker of good prognosis(P=0.03).The proportion of clinically advanced UC with basal-like type was significantly higher than that of luminal-like type(78.4％vs 53.4％,P=0.033).Among the histologic variants,UC with neuroendocrine differentiation(100％),sarcomatoid carcinoma(80.0％)and squamous differentiation(77.8％)were basal-like type.All plasmacytoid and lymphoepithelioma-like types,as well as 81.8％of micropapillary UC.Among the null phenotypes,the differential variant predominated(66.7％).Compared with the luminal-like type,although the prognosis of basal-like UC was worse,there was no sta-tistically significant difference(P＞0.05).Conclusion Patients with CK20-expressing UC had a significantly better prognosis.The main histologic variants types of basal-like type and coelomofacial type are different.Molecular typing of UC using immunohistochemical markers is suggestive of clinical staging and prognosis of patients.

Purpose To investigate the relationship between the expression of POSTN and NECTIN-3 in urothelial carcinoma(UC)and its clinicopathologic features and prognosis.Methods Clinical data of 115 UC patients were col-lected.EnVision two-step method was used for immunohistochemical analysis to determine the expression of POSTN and NECTIN-3 in UC and their correlation with clinicopathological features and prognosis.Transcriptomic data from TCGA database were used to analyze the correlation between the expression of POSTN and NECTIN-3 in bladder cancer and the pathological stage and prognosis of bladder cancer.qPCR and Western blot were used to detect the expression levels of POSTN and NECTIN-3 in tumor tissues and adjacent tissues of patients.Results TCGA database analysis showed that the expression level of NECTIN-3 in urinary bladder urothelial carcinoma(UBUC)was significantly lower than that in paracancer tissues,and POSTN expression was positively correlated with pathological stage.Prognostic a-nalysis showed that POSTN expression was negatively correlated with the overall survival of UBUC(P＞0.05),and NECTIN-3 expression was negatively correlated with disease-free survival of UBUC(P＞0.05).The experimental re-suits showed that patients with positive POSTN expression were more prone to perineural invasion[25 cases(86.2％)vs 4 cases(13.8％),P=0.019],vascular invasion[36 cases(83.7％)vs 7 cases(16.3％),P=0.007],and lymph node metastasis[24 cases(88.9％)vs 3 cases(11.1％),P=0.033].Additionally,the positive expression rate of POSTN in UBUC was significantly higher than that in upper tract urothelial carcinoma(UTUC)(75.0％vs 54.3％,P=0.028).Higher expression levels of POSTN and NECTIN-3 were associated with shorter overall survival,but the difference was not statistically significant(P＞0.05).Conclusion There is no significant correlation between NECTIN-3 and the clinicopathological features and prognosis of urothelial carcinoma,while the expression of POSTN is correlated with the invasive clinicopathological features of UC,which has certain suggestive significance for clinical stage and prognosis.

Objective: To explore the effects of long non-coding RNA (LncRNA) MIR22HG on proliferation，apoptosis and inflammatory response of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and its molecular mechanism． Methods: Synovial tissue samples were collected from 37 RA patients and 30 joint trauma patients in our hospital，and the expression levels of MIR22HG and miR-22-5p in synovial tissue were detected by qRT-PCR. RA-FLSs in human was isolated ，cultured and identified in vitro． MIR22HG siRNA interference plasmid (si-MIR22HG) and its negative control plasmid (si-NC) ，miR-22-5p inhibitor and its negative control (inhibitorNC) were transfected into RA-FLSs respectively or simultaneously．The expression levels of MIR22HG and miR- 22-5p were detected by qRT-PCR. CCK-8 was used to detect the proliferation activity of cells in various groups. Annexin Ⅴ- FITC / PI was used to detect the apoptosis rates of cells in various groups．ELISA was used to detect the levels of TNF-α , IL-1 β and IL-6 in the supernatant of cells in various groups．Western blot was used to detect the protein expression levels of Bcl-2，Bax and Cleaved caspase-3 of cells in various groups．The targeting relationship between MIR22HG and miR-22-5p was verified by dual luciferase reporter gene assay. Results : Compared with joint trauma patients，the expression level of MIR22HG in synovial tissues of RA patients increased (P＜0. 05) ， while the expression level of miR-22-5p decreased (P＜0. 05) ．Interference with MIR22HG inhibited the proliferation activity of RA-FLSs，decreased the levels of TNF-α , IL-1 β and IL-6 in cell supernatant and the protein expression level of Bcl-2 in cells (P＜0. 05) ，and increased the apoptosis rate，the expression level of miR-22-5p and the protein expression levels of Bax and Cleaved casepase-3 (P ＜0. 05 ) ．However，inhibition of miR-22-5p expression reversed the effects of MIR22HG gene silencing on proliferation，apoptosis and inflammation of RA-FLSs (P＜0. 05) ．Dual luciferase reporting assay showed that miR-22-5p was a potential downstream miRNA target of MIR22HG． Conclusion MIR22HG is highly expressed in synovial tissues of RA patients，and it may promote the proliferation and the inflammatory response of RA-FLSs and inhibit cell apoptosis by down regulating the expression of miR-22-5p.

Purpose To explore the clinicopathological re-lationship between tumor budding and KRAS,NRAS,BRAF gene mutations and MSI status in colorectal adenocarcinoma and their clinical significance.Methods The clinical data of 237 cases of colorectal adenocarcinoma were collected to interpret tumor budding.RT-PCR was used to detect the gene mutations of KRAS,NRAS,BRAF in 229 cases and to analyze the corre-lation between tumor budding and gene mutations.MSI was de-tected by PCR and its relationship with tumor budding was ana-lyzed.Results Of the 237 patients,147 showed low-to medi-um-grade tumor budding and 90 showed high-grade tumor bud-ding.Tumor budding was associated with tumor size,vascular involvement,perineural invasion,tumor differentiation,lymph node metastasis,tumor nodule formation,tumor recurrence and TNM staging(P＜0.05),while it was not associated with age,sex and location.Single factor logistic regression analysis showed that tumor budding was associated with the risk of lymph node metastasis(P＜0.05),while multivariate logistic regres-sion analysis showed that tumor budding was an independent pre-dictor of lymph node metastasis in colorectal adenocarcinoma(P＜0.05).Of the 229 cases,the mutation rate of KRAS,NRAS and BRAF was 42.4％,2.6％and 3.1％,respectively.A-mong KRAS,NRAS and BRAF mutation cases,the proportion of high-grade tumor budding was 56.7％,33.3％and 14.3％,respectively.Tumor budding was associated with mutations in the Kras 12 and Kras 13 codons,as well as KRAS total muta-tions(P＜0.05).However,tumor budding had no relationship with NRAS and BRAF.In the high-grade budding tumors,KRAS mutations were mainly KRAS codons 12 and 13.Among the cases with KRAS mutation,the disease-free survival time and total survival time of the cases with high-grade tumor bud-ding were significantly shorter(P＜0.05).Of the 237 patients,the rate of MSI-H was 6.8％and only 2 out of 16 MSI-H pa-tients had high-grade tumor budding.There was a negative cor-relation between tumor budding and MSI status(r=-0.143,P＜0.05).Conclusion Tumor budding is related to the muta-tions in the Kras 12 and Kras 13 codons,as well as total KRAS mutations and MSI status.Tumor budding is also related to the prognosis of patients with colorectal adenocarcinoma,which can provide a reference for their outcome judgment.

Purpose To investigate the expression of GATA3 in breast tumors and its clinical significance. Methods Immunohisto-chemistry EnVision method was used to detect the expression of GATA3 protein in 132 cases of breast malignant tumor tissue, 29 cases of breast benign tumor tissue, 35 cases of breast carcinoma adjacent tissue. Besides, the GATA3 expression level was compared with several clinicopathological parameters. Result (1) All the breast normal tissues expressed GATA3, while 77% of the breast cancer tissue were found to be GATA3 positive. (2) GATA3 did not expressed in diffuse large B cell lymphoma and spindle cell malignant tumor of breast. (3) In the triple negative breast cancer, the expression of GATA3 was lower than that of any other subtypes of breast carcinoma (χ2 =29. 354, P<0. 001). Conclusion The positive expression of GATA3 is correlated to classification and grade in breast tumor. Detection of the expression of this biological maker may provide a valuable marker for the differential diagnosis and prog-nostic of breast carcinoma.

Purpose To measure the nuclear morphological parameters of breast cancer to study the relationship between nuclear mor-phological parameters and ER, PR, HER-2 expression, and clinicopathologic features of breast carcinoma. Methods 388 cases of breast cancer specimens were collected and molecular classification was made according to ER, PR and HER-2 expression. the nucleus parameters were measured by image analysis software after HE staining. The difference among groups was statistically analysed, and follow-up was done by phone or by hospitalization. Results Among the 4 groups of breast cancer case, the differences of circle diame-ter, area and perimeter edges of the nucleus were statistically significant (P<0.05). Nuclear morphometric quantitation between ER+/PR+ patients and ER-/PR- patients was statistically significantly differentice (P<0.05). The majority of patients with ER-/PR- were histological gradeⅢand poor survival rate (P<0.05). The disease-free survival in Luminal A type was higher than that of Basal-like type (P<0.05), and its overall survival was higher than HER-2 over-expression (P<0. 05) and Basal-like type (P<0.05) . Conclusion The nucleus morphological quantitation in breast cancer is of significant difference, which has certain reference value in its molecular typing. The result of ER, PR and HER-2 expression, combined with nuclear morphology measurement, are meaningful to the treatment and assessment of prognosis.