scholarly journals Significance of EZH2 and BMI-1 Protein Expression in Carcinogenesis of Colon Serrated Adenoma

2021 ◽  
Vol 5 (4) ◽  
pp. 27-30
Author(s):  
Kai Zhao

Objective: To observe the significance of EZH2 and BMI-1 protein expression in the carcinogenesis process of colon serrated adenoma (SSA/P). Methods: Hematoxylin-eosin (HE) staining was used to observe the morphological characteristics of normal tissues, hyperplastic polyp (HP), SSA/P and colon cancer. Immunohistochemical staining was used to detect the expression of EZH2 and BMI-1 protein. The relative expression of EZH2 and BMI-1 was detected by qRT-PCR. Results: Compared with normal tissues, HP and colon cancer tissues, SSA/P showed serrated glandular hyperplasia, glandular dilatation, and deep nuclear staining, which had certain atypia. The positive expression rates of EZH2 and BMI-1 protein were 53.3% and 56%, which were close to those of colon cancer (66.7% and 76.6%) and higher than those of normal group and HP (16% and 8%, P < 0.05). The relative expression of EZH2 and BMI-1 in SSA/P tissue was significantly higher than that in normal group and HP, but lower than that in carcinogenesis group (P<0.05). Conclusion: EZH2 and BMI-1 play an important role in the carcinogenesis of colon serrated adenoma, and can be used as the primary screening index before carcinogenesis.

2019 ◽  
Vol 17 ◽  
pp. 205873921982823
Author(s):  
Yuelou Yang ◽  
Xiangjun Jiang ◽  
Dong Li ◽  
Feiyan Wang ◽  
Qun Yang ◽  
...  

To investigate the correlation and clinical significance between programmed cell death factor 4 (PDCD4) and epidermal growth factor receptor 2 (Her-2) expressions and clinicopathological parameters in patients with gastric cancer, a total of 65 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expressions were detected by SP immunohistochemical staining, and 50 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expression quantities were detected by Western blot, in order to analyze the relationship between the positive expressions of PDCD4 and Her-2 protein and the clinicopathological features of patients with gastric cancer. The results showed that the positive rate of PDCD4 protein expression in gastric cancer tissues was 7.7%, which was significantly lower than that in the corresponding normal tissues, that is, 77.5% ( P < 0.05); the positive rate of Her-2 expression was 41.5%, which was significantly higher than that of the corresponding normal tissues, which is 2.5% ( P < 0.05). The Western blot test showed that the expression of PDCD4 protein in gastric cancer was 0.3105 ± 0.0073, which was significantly lower than that in the corresponding normal tissues, that is, 0.9428 ± 0.0127 ( P < 0.05); the expression level of Her-2 protein in gastric cancer tissues was 0.9428 ± 0.0127, which was significantly higher than that of the corresponding normal mucosa, which is 0.2054 ± 0.0264 ( P < 0.05). The positive expressions of PDCD4 (5/65) and Her-2 (27/65) were significantly correlated with the differentiation degrees and TNM stages of gastric cancer ( P < 0.05). However, no significant correlation can be observed from Table 2 ( P > 0.05), regarding sex, age, tumor size, and lymph node metastasis. Our research claimed that PDCD4 and Her-2 may play an important role in the invasion and metastasis of gastric cancer, which has a negative correlation with biological behaviors of gastric cancer. The low expression of PDCD4 and the high expression of Her-2 in gastric cancer may promote the occurrence and progression of cancer. The PDCD4 and Her-2 test can be used as an index to evaluate the malignant biological behaviors of gastric cancer and prognosis, and provide a theoretical basis for targeted therapy.


2013 ◽  
Vol 73 (7) ◽  
pp. 2368-2378 ◽  
Author(s):  
Amanda F. Swindall ◽  
Angelina I. Londoño-Joshi ◽  
Matthew J. Schultz ◽  
Naomi Fineberg ◽  
Donald J. Buchsbaum ◽  
...  

Author(s):  
Yang zhi Jiang ◽  
Qing Guo Tao ◽  
fei yan Zhu

BACKGROUND AIM To explore the correlation between the expression of miRNA-135a and Bach1 in colorectal cancer tissue and the patient's clinical information.  Methods   60 patients with colorectal carcinoma were treated as a control group. Real-time quantitative PCR assays and immunohistochemistry method were performed to detect the expression of miRNA-135a and Bach1 in 60 colorectal carcinomas and adjacent normal tissues, and the clinical and pathological classifications had also been investigated. The SPSS 19.00 software was used. All data represented mean±SD of three independent experiments. P&lt;0.05 was considered statistically significant. Results  miRNA-135a expression levels increased significantly in the colon cancer tissues compared with the non-tumor control tissues(P&lt;0.01). miRNA-135a expression levels were higher in stage III/IV than in stage I/II colon cancer patients. The expression level of Bach1 in colorectal cancer was significantly lower(P&lt;0.01). Bach1 and miRNA-135a were negatively correlated.  Conclusions:  The levels of miRNA-135a and Bach1 were opposite, the over-expression of miRNA-135a might downregulated the expression of Bach1, which might be involved in the pathogenesis of colorectal cancer.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 417-417
Author(s):  
J. Stoehlmacher ◽  
C. Kohne ◽  
M. Mauer ◽  
E. Goekkurt ◽  
M. P. Lutz ◽  
...  

417 Background: Pts with stage III colon cancer have been treated with either infusional 5-FU or bolus 5- FU in the adjuvant setting (PETACC-2 trial). DUTPase and TS demonstrated potential as predictive markers for 5-FU efficacy in pts with advanced colorectal cancer. Here we aimed to explore whether TS or dUTPase protein levels may predict recurrence of disease for stage III colon pts treated with 5-FU. Methods: Tumor (T) blocks of 324 pts were analyzed for protein expression of dUTPase and TS. For analysis monoclonal antibodies DUT415 and TS106 were used. T were evaluated by two investigators as follows. Only nuclear staining for both, TS and dUTPase, was analyzed. If tumor cells (TC) showed a nuclear dUTPase expression in >10% of cells, the sample was scored positive. Positive nuclear staining for >20% of TC, when using the TS antibody, determined a positive sample. Results: Analysis for dUTPase was successful in 308 samples (95.1%, 308/324). 263 out of those 308 pts showed a positive dUTPase expression (85.3%). 297/324 samples (91.7%) could be evaluated for TS. In the TS group 62.3% (185/297) showed a positive expression for TS protein. In 281 cases analyses were successful for both TS and dUTPase. We observed a significant association between dUTPase and TS expression with a majotity of 71.4% (172/241) dUTPase positive T also being positive for TS as compared to 32.5% (13/40) of dUTPase negative T that showed positivity for TS protein expression (p< 0.0001). Of pts with dUTPase positive T 64.7% showed no recurrence of disease as compared to 44.7% of those with dUTPase negative T 5 years after completion of therapy (HR 0.61 [95% CI 0.36, 1.03], p=0.06). No associations between TS and DFS were observed. Both TS and dUTPase expression did not correlate with OS in this patient cohort. Conclusions: High TS protein levels appeared to be significantly correlated with high protein levels of dUTPase in stage III colon cancer pts. Neither dUTPase nor TS protein levels appeared to be significantly associated with DFS or OS of stage III colon cancer pts that received adjuvant chemotherapy with 5-FU. No significant financial relationships to disclose.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7431
Author(s):  
Yujing Li ◽  
Beilei Zeng ◽  
Yunhai Li ◽  
Chong Zhang ◽  
Guosheng Ren

Background Rho GTPase-activating protein 10 (ARHGAP10), which catalyzes the conversion of active Rho GTPase to the inactive form, is downregulated in some cancers. However, little is known about ARHGAP10 in breast cancer. Methods The transcriptional expression level of ARHGAP10 in breast cancer was analyzed with the data downloaded from The Cancer Genome Atlas (TCGA) and Oncomine, then verified by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) in 30 pairs of breast cancer tissues and the corresponding adjacent normal tissues. ARHGAP10 protein expression was examined by immunohistochemistry (IHC) in 190 breast cancer and 30 corresponding adjacent normal breast tissue samples. The associations between ARHGAP10 expression and clinicopathological characteristics of patients were analyzed, and Kaplan–Meier Plotter was used to assess the relationship between ARHGAP10 and relapse-free survival (RFS). Different expression levels of ARHGAP10 in response to chemotherapy agents were determined by GEO2R online tool. The potential biological functions of ARHGAP10 were analyzed by Gene Set Enrichment Analysis (GSEA) using data downloaded from TCGA. Results ARHGAP10 mRNA and protein expression was lower in breast cancer tissues than in adjacent normal tissues. Low expression of ARHGAP10 was associated with advanced clinical TNM (cTNM) stage (pb = 0.001) and high Ki-67 index (p = 0.015). Low expression of ARHGAP10 indicated worse RFS (p = 0.0015) and a poor response to chemotherapy (p = 0.006). GSEA results showed that ARHGAP10 was involved in signaling pathways including protein export, nucleotide excision repair, base excision repair, focal adhesion, JAK-STAT pathway and the actin cytoskeleton.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8562 ◽  
Author(s):  
Haibo Yao ◽  
Fang Lu ◽  
Yanfei Shao

Background The E2F family is a group of genes encoding a series of transcription factors in higher eukaryotes and participating in the regulation of cell cycle and DNA synthesis in mammals. This study was designed to investigate the role of E2F family in colon cancer. Methods In this study, the transcriptional levels of E2F1-8 in patients with colon cancer from GEPIA was examined. Meanwhile, the immunohistochemical data of the eight genes were also obtained in the The Human Protein Atlas website. Additionally, we re-identified the mRNA expression levels of these genes via real time PCR. Furthermore, the association between the levels of E2F family and stage plot as wells overall survival of patients with colon cancer were analyzed. Results We found that the mRNA and protein levels of E2F1, E2F2, E3F3, E2F5, E2F7 and E2F8 were significantly higher in colon cancer tissues than in normal colon tissues while the expression levels of E2F4 and E2F6 displayed no significant difference between colon cancer tissues and normal tissues. Additionally, E2F3, E2F4, E2F7 and E2F8 were significantly associated with the stages of colon cancer. The Kaplan-Meier Plotter showed that the high levels of E2F3 conferred a worse overall survival and disease free survival of patients with colon cancer. Also, high levels of E2F4 resulted in a worse overall survival. Conclusion Our study implied that E2F3, E2F4, E2F7 and E2F8 are potential targets of precision therapy for patients with colon cancer while E2F1, E2F2, E3F3, E2F5, E2F7 and E2F8 are potential biomarkers for the diagnosis of colon cancer.


2021 ◽  
Vol 20 ◽  
pp. 153303382110194
Author(s):  
Junying Xu ◽  
Xuejing Yang ◽  
Yong Mao ◽  
Jie Mei ◽  
Huiyu Wang ◽  
...  

In recent years, immunotherapies have emerged as effective therapeutic strategies for treating human cancers. However, accumulating evidence has revealed an inconsistency between the response to immune checkpoint inhibitors and programmed death ligand 1 (PD-L1) expression status detected by immunohistochemistry staining. Recent research has revealed that the removal of N-Linked glycosylation significantly enhanced PD-L1 detection, resulting in both more accurate PD-L1 quantification and clinical outcome prediction. In the present study, we evaluated natural and deglycosylated PD-L1 expression in colon cancer using the PD-L1 28–8 antibody. The results of the present study validated the hypothesis that PD-L1 had a higher expression in colon cancer tissues compared with normal tissues. Additionally, colon tumors with defective mismatch repair tended to express higher PD-L1 than those without. Most importantly, the results of the present study indicated that the removal of N-linked glycosylation remarkably enhanced PD-L1 detection. Moreover, the PD-L1 signal intensity of samples with a low natural PD-L1 signal was enhanced more remarkably than that of samples with high signal intensity. Overall, our research provides an improved strategy for patient stratification for anti-PD-1/PD-L1 therapy, which deepens the clinical significance of this established strategy for treatment of colon cancer.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ji-lin Li ◽  
Ke-zhi Li ◽  
Ming-zhi Xie ◽  
Yan-ping Tang ◽  
Yin-lin Tang ◽  
...  

Background. The association of miR-28-5p with colon cancer remains to be elucidated. This study aimed to determine the clinical significance and prognostic value of miR-28-5p in colon cancer. Methods. We retrospectively analyzed the data of miR-28-5p in colon adenocarcinoma data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and the data was divided into cancer group and normal group, respectively. Forty colon cancer tissues and adjacent normal tissues were collected and tested by qRT-PCR methods. The difference of the miR-28-5p expression between colon cancer and normal tissues was compared. The clinical significance of miR-28-5p in colon cancer and the association with the survival were determined. The predictive value of miR-28-5p in clinical features was determined using receiver operating characteristic curve. The target genes of miR-28-5p were identified, and the functional of target genes was performed using bioinformatics analysis. Results: The expression of miR-28-5p was increased in colon cancer tissues compared with normal controls (p=0.037). The expression of miR-28-5p was significantly increased in tissues with distant metastases compared with that without distant metastases (p=0.026). Patients with high expression of miR-28-5p have a shorter survival time than those with low expression (p=0.004). Cox analysis showed that miR-28-5p was an independent predictor for the survival of patients (p=0.014). Combination of miR-28-5p with TNM stage and clinical stage can improve the prognostic value for the patients (p<0.05). miR-28-5p has a moderate predictive value in predicting the TNM stage and clinical stage (T stage: AUC=0.515; N stage: AUC=0.523, M stage: AUC=0.572; clinical stage: AUC=0.539). 711 potential target genes of miR-28-5p were screened; their function and pathways were identified. Conclusions: This study demonstrated that miR-28-5p was increased in colon cancer and can be an independent indicator for the overall survival in patients with colon cancer.


2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Chunyang Wang ◽  
Yidan Wu ◽  
Yunqi Liu ◽  
Fushun Pan ◽  
Huijuan Zeng ◽  
...  

Background: RBMS3 (RNA-binding motif, single-stranded-intervacting protein 3) acts as a tumor-suppressive gene in a number of human cancers, however, its role in breast cancer is not fully understood. This study aimed to investigate the expression and clinicopathological significance of RBMS3 in breast cancer. Methods: A total of 998 breast cancer tissue samples in The Cancer Genome Atlas (TCGA) database with survival outcomes were divided into high RBMS3 expression and low expression groups using the median as the cutoff. Clinicopathological characteristics and prognosis were compared between the 2 groups. Results: TCGA showed that RBMS3 mRNA was downregulated in breast cancer tissues, and RBMS3 downregulation was correlated with poor prognosis. Immunohistochemistry staining of 127 paraffin-embedded breast cancer tissues showed that RBMS3 protein was localized in the cytoplasm and nucleus; however, nuclear staining was present in 90.0% of normal breast tissues but only 28.3% of breast cancer tissues. Decreased RBMS3 protein expression was significantly correlated with estrogen receptor (ER)-negative status and death at final follow-up. Patients with lower RBMS3 protein expression had substantially shorter survival than those with higher RBMS3 expression. Univariate and multivariate analysis indicated that the combination of RBMS3 expression and ER status (a variable designated as “cofactor”) was an independent prognostic factor in patients with breast cancer (hazard ratio [HR] = 0.420, 95% confidence interval [CI]: 0.223-0.791, P = 0.007). Conclusion: RBMS3 downregulation was correlated with poor prognosis in breast cancer patients, and the combination of RBMS3 expression and ER status was an independent prognostic factor.


2021 ◽  
Vol 22 (3) ◽  
pp. 1043
Author(s):  
Yunna Lee ◽  
Elise L. Ma ◽  
Marisa Patel ◽  
Gayoung Kim ◽  
Cody Howe ◽  
...  

The neuroendocrine circuit of the corticotropin-releasing hormone (CRH) family peptides, via their cognate receptors CRHR1 and CRHR2, copes with psychological stress. However, peripheral effects of the CRH system in colon cancer remains elusive. Thus, we investigate the role of CRHR1 and CRHR2 in colon cancer. Human colon cancer biopsies were used to measure the mRNA levels of the CRH family by quantitative real-time PCR. Two animal models of colon cancer were used: Apcmin/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. The mRNA levels of CRHR2 and UCN III are reduced in human colon cancer tissues compared to those of normal tissues. Crhr1 deletion suppresses the tumor development and growth in Apcmin/+ mice, while Crhr2 deficiency exacerbates the tumorigenicity. Crhr1 deficiency not only inhibits the expression of tumor-promoting cyclooxygenase 2, but also upregulates tumor-suppressing phospholipase A2 in Apcmin/+ mice; however, Crhr2 deficiency does not change these expressions. In the AOM/DSS model, Crhr2 deficiency worsens the tumorigenesis. In conclusion, Crhr1 deficiency confers tumor-suppressing effects in Apcmin/+ mice, but Crhr2 deficiency worsens the tumorigenicity in both Apcmin/+ and AOM/DSS-treated mice. Therefore, pharmacological inhibitors of CRHR1 or activators of CRHR2 could be of significance as anti-colon cancer drugs.


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