Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity

AIM: To evaluate the role of N-myc downstream-regulated gene 1 (NDRG1) expression in prognosis and survival of colorectal cancer patients with different ethnic backgrounds. METHODS: Because NDRG1 is a downstream target of p53 and hypoxia inducible factor-1α (HIF-1α),we examined NDRG1 expression together with p53 and HIF-1α by immunohistochemistry. A total of 157 colorectal cancer specimens including 80 from Japanese patients and 77 from US patients were examined. The correlation between protein expression with clinicopathological features and survival after surgery was analyzed.in colorectal tumor compared with normal epithelium in both Japanese and US patient groups. Expression of NDRG1 protein was significantly correlated with lymphatic invasion,venous invasion,depth of invasion,histopathological type,and Dukes' stage in Japanese colorectal cancer patients. NDRG1 expression was correlated to histopathological type,Dukes' stage and HIF-1α expression in US-Caucasian patients but not in US-African American patients. Interestingly,Kaplan-Meier survival analysis demonstrated that NDRG1 expression correlated significantly with poorer survival in US-African American patients but not in other patient groups. However,in p53-positive US cases,NDRG1 positivity correlated significantly with better survival. In addition,NDRG1 expression also correlated significantly with improved survival in US patients with stages Ⅲ and Ⅳ tumors without chemotherapy. In Japanese patients with stages Ⅱ and Ⅲ tumors,strong NDRG1 staining in p53-positive tumors correlated significantly with improved survival but negatively in patients without chemotherapy. CONCLUSION: NDRG1 expression was correlated with various clinicopathological features and clinical outcomes in colorectal cancer depending on the race/ethnicity of the patients. NDRG1 may serve as a biological basis for the disparity of clinical outcomes of colorectal cancer patients with different ethnic backgrounds.     

COX-2 expression in gastric cancer and its relationship with angiogenesis using tissue microarray

AIM： To explore the expression and clinicopathological significance of cyclooxygenase-2 （COX-2） and microvessel density （MVD） in gastric carcinogenesis, and to investigate their roles in the invasion and the relationship between biological behaviors and prognosis of gastric cancer.
METHODS： Using Envision immunohistochemistry, COX-2 and CD34 expressions in gastric cancer tissue array were examined. MVD was counted and the relationship between the biological behaviors and prognosis was analyzed.
RESULTS： The expression of COX-2 in gastric cancer tissue was significantly higher than that in normal mucosa （χ^2 = 12.191, P 〈 0.05）. The over-expression of COX-2 in gastric cancer was obviously related to metastasis and depth of invasion （χ^2 = 6.315, P 〈 0.05）, but not related to the histological type and Borrmann type （χ^2 = 5.391 and χ^2= 2.228, respectively）. Moreover, MVD in gastric cancer tissues was significantly higher than that in the normal mucosa （65.49 ± 20.64 vs 36.21 ± 18.47, t/F = 7.53, P 〈 0. 05）. MVD was related to the histologic type and metastasis （t/F= 3.68 and t/F = 4.214, respectively, P 〈 0. 05）, but not related to the depth of invasion and Borrmann type （t/F = 0.583 and t/F = 0.459, respectively）. MVD in COX-2-positive tissues was markedly higher compared to COX-2-negative tissues, indicating a positive correlation between COX-2 expression and MVD （t = 13.12, P 〈 0. 05）.
CONCLUSION： Tissue microarray （TMA） is a powerful tool for rapid identification of the molecular alterations in gastric cancer. COX-2 expression, via inducingangiogenesis, may play an important role in gastric carcinogenesis. It could be served as a determinant factor for clinical prognosis and curative effect.     

Mad2 and p53 expression profiles in colorectal cancer and its clinical significance

AIM: To investigate the expression of tumor suppressor gene p53 and spindle checkpoint gene Mad2, and to demonstrate their expression difference in colorectal cancer and normal mucosa and to evaluate its clinical significance.METHODS: Westemn blot and immunohistochemistry methods were used to analyze the expression of Mad2 in colorectal cancer and its corresponding normal mucosa. The expression of p53 was detected by immunohistochemistry method in colorectal cancer and its corresponding normal mucosa.RESULTS: Mad2 was significantly overexpressed in colorectal cancer compared with corresponding normal mucosa (P＜0.001), and it was not related to the differentiation of adenocarcinoma and other dinical factors (P＞0.05).The ratio of Mad2 protein in cancer tissue (C) to that in its normal mucosa tissue (N) was higher than 2, which was more frequently observed in patients with lymph gland metastasis (P＜0.05). p53 protein expression was not observed in normal mucosa. The rate of p53 positive expression in adenocarcinomas was 52.6%. There was a significant difference between adenocarcinomas and normal mucosa(P＜0.001), which was not related to the differentiation degree of adenocarcinoma and other clinical factors (P＞0.05).CONCLUSION: Defect of spindle checkpoint gene Mad2and mutation of p53 gene are involved mainly in colorectal carcinogenesis and C/N＞2 is associated with prognosis of colorectal cancer.     

Relationship between anemia and clinical features and prognosis of advanced lung cancer patients

正Objective To investigate the relationship of anemia and clinicopathological features and prognosis of patients with advanced lung cancer.Methods The clinical data of741 patients with stageⅢ-Ⅳlung cancer were collected and analyzed retrospectively. We analyzed the incidence and type of anemia during the natural course of lung cancer patients, and its relationship with the gen-     

Cyclooxygenase－2 expression and angiogenesis in colorectal cancer

AIM: Cyclooxygenase-2 is involved in a variety of important cellular functions, including cell growth and differentiation,cancer cell motility and invasion, angiogenesis and immune function. However, the role of cyclooxygenase-2 as an angiogenic factor in colorectal cancer tissue is still unclear.We investigated the relationship between cyclooxygenase2 and angiogenesis by analyzing the expression of cyclooxygenase-2 in colorectal cancer tissue, as well as its association with vascular endothelial growth factor (VEGF)and microvascular density (MVD). METHODS: The expression of cydooxygenase-2, VEGF, as well as MVD was detected in 128 cases of colorectal cancer by immunohistochemical staining. The relationship between the cydooxygenase-2 and VEGF expression and MlVD was evaluated.Our objective was to determine the effect of cyclooxygenase2 on the angiogenesis of colorectal cancer tissue. RESULTS: Among 128 cases of colorectal cancer, 87 were positive for cyclooxygenase-2 (67.9 %), and 49 for VEGF (38.3 %), respectively. The microvessel counts ranged from 23 to 142, with a mean of 51.7 (standard deviation, 19.8). The expression of cydooxygenase-2 was correlated significantly with the depth of invasion, stage of disease, metastasis (lymph node and liver), VEGF expression and MlVD. Patients in T3-T4, stage Ⅲ-ⅣV and with metastasis had much higher expression of cydooxygenase-2 than patients in T1-T2, stage Ⅰ-Ⅱ and without metastasis (P＜0.05). The positive expression rate of VEGF (81.6 %) in the cyclooxygenase-2 positive group was higher than that in the cyclooxygenase-2 negative group (18.4 %,P＜0.05). Also, the microvessel count (56±16) in cyclooxygenase-2 positive group was significantly higher than that in cyclooxygenase-2 negative group (43±12, P＜0.05). The microvessel count in tumors with positive cyclooxygenase-2and VEGF was the highest (60±18, 41-142, P＜0.05), whereas that in tumors with negative cyclooxygenase-2 and VEGF wasthe lowest (39±16, 23-68, P＜0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by madulating the angiogenesis in colorectal cancer tissue and used as a possible biomarker.     

Clinicopathological significance of p53 and mdm2 protein expression in human pancreatic cancer

AIM: To study the clinicopathological significance of p53 and mdm2 protein expression in human pancreatic cancer. METHODS: To investigate the expression of p53 and mdm2 in pancreatic cancer by immunohistochemistry, and the relationships between the p53 and mdm2 protein expression and clinicopathological parameters in pancreatic cancer. RESULTS: The positive expression of p53 protein was found in 40 of 59 patients (67.8%) and that of mdm2 protein in 17 of 59 patients (28.8%). No obvious relationships were found between p53 as well as mdm2 expression and sex, tumor site,TNM staging and histological differentiation. p53 expression was increased in patients younger than 65 years old, while mdm2 had no relationship with age. The survival time of the patients with the positive expression of p53 and mdm2 proteins was obviously shorter than the other groups. CONCLUSION: Both p53 and mdm2 presented relatively high expression in human pancreatic cancer.The overexpression of p53 and mdm2 might reflect the malignant proliferation of pancreatic cancer and their co-expression might be helpful to evaluate the prognosis of the patients with pancreatic cancer.     

Connective tissue growth factor expression hints at aggressive nature of colorectal cancer

BACKGROUND Connective tissue growth factor(CTGF)is a mediator of transforming growth factor-beta signaling and plays a key role in connective tissue remodeling,inflammatory processes and fibrosis in various illnesses including cancer.AIM To investigate the role of CTGF in colorectal cancer(CRC)progression and to compare the CTGF expression with different clinicopathological parameters.METHODS Real-time polymerase chain reaction,immunohistochemistry and Western blotting was performed to evaluate the CTGF expression and the results were statistically analyzed against the clinicopathological variables of patient data using STATA software version 16.RESULTS CTGF expression levels in tumor specimens were significantly higher than their paired normal specimens.The higher protein expression levels showed a significant association with smoking,staging,tumor grade,invasion depth,necrosis of tumor tissue,and both lymphovascular and perineural invasion.As per the cox regression model and classification tree analysis,tumor-nodemetastasis stage and perineural invasion were important predictors for CTGF expression and prognosis of CRC patients.Survival analysis indicated that CTGF overexpression was associated with poorer overall and disease-free survival.CONCLUSION Expression of CTGF was increased in CRC and was linked with poor overall and disease-free survival of CRC patients.These findings support prior observations and thus CTGF may be a possible prognostic marker in CRC.     

Role of COX-2 in carcinogenesis of colorectal cancer and its relationship with tumor biological characteristics and patients′prognosis

AIM: Recent clinical epidemiological studies havedemonstrated the preventive effect of non-steroidal anti-inflammatory drugs (NSAIDs) against colorectal cancer.The underlying mechanism might be the inhibition of rate-limiting enzyme cyclooxygenase-2 (COX-2) in metabolismof arachidonic acid. The role of COX-2 in carcinogenesisof colorectal cancer and its relationship with tumorbiological characteristics and patients′ prognosis stillremain unclear. This study was to investigate the role ofCOX-2 expression in carcinogenesis of colorectal cancerand its relationship with tumor biological characteristicsand patients′ prognosis.METHODS: A total of 139 colorectal cancers and 19adenomas surgically treated in School of Oncology, PekingUniversity, from January 1993 to September 2001 wereretrospectively studied. COX-2 expression was detected withtissue microarray (TMA) and immunohistochemistry (IHC)procedure. The association between COX-2 expression andclinicopathological features and its influence on patients′prognosis were studied.RESULTS: COX-2 expression was strong in colorectal cancer,moderate in adenoma and weak in normal mucosa, whichdemonstrated statistically significant difference (x2=46.997,P＜0.001). COX-2 expression had no association withclinicopathological features such as gross type,differentiation, invasion depth, vessel emboli and TNMstaging. Cox proportional hazards modeling analysis and Logrank test revealed no prognostic role of COX-2 expressionin colorectal cancer patients.CONCLUSION: COX-2 may play an important role in theearly stage of carcinogenesis, and its expression in colorectalcancer is not associated with clinicopathological features and patients′ prognosis.     

Cyclooxygenase-2 expression is associated with well-differentiated and intestinal-type pathways in gastric carcinogenesis

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) expression appears to be increased in several different types of human cancers, suggesting that the presence of COX-2 is associated with carcinogenesis. Recently, increased expression of COX-2 has been frequently detected in gastric cancer, and this may have prognostic significance. In the present study, we aimed to analyze the expression of COX-2 in a much larger sample to determine whether COX-2 expression is related to the clinicopathological features and survival rates of patients with gastric cancer. METHODS: We investigated 140 patients with gastric cancer who underwent surgery between January 1992 and December 1993 and examined the expression of COX-2 in human gastric cancer tissue by immunohistochemistry. RESULTS: COX-2 expression was present in the cytoplasm of tumor cells but not in normal gastric epithelia. Positive expression of COX-2 was detected in 86 of 140 gastric cancers analyzed (61.4%). Positive expression of COX-2 correlated with the depth of tumor invasion (p = 0.015). However, there was no association between COX-2 expression and tumor stage or status of lymph node or distant metastasis. Furthermore, COX-2 expression was not associated with patient survival (p = 0.816). Positive expression of COX-2 occurred more frequently in intestinal than in diffuse or mixed types of cancer and correlated with tumor differentiation (p < 0.001, p = 0.001, respectively). CONCLUSION: These results suggest that COX-2 may play an important role in the evolution of gastric carcinogenesis and be associated with well-differentiated and intestinal type pathways in gastric carcinogenesis. However, COX-2 expression seems to be less useful for establishing prognosis for gastric cancer.     

Expression of cyclooxygenase-2 protein in colorectal carcinomas

Summary Background. Overexpression of cyclooxygenase-2 (COX-2) has been demonstrated in various human cancers, including colorectal cancer. Thus, overexpression of COX-2 may be involved in the growth and progression of cancer, and this may have prognostic significance. Aim. The aim of our study is to evaluate the expression of COX-2 in colorectal cancer tissue, and to examine the relationship of its expression to various clinicopathological parameters and patient survival. Methods. Formalin-fixed, paraffin-embedded tissue blocks were obtained from 60 patients who underwent surgery for colorectal carcinoma in 1995 at the Chonnam National University Hospital in Gwangju, Korea. We have used an immunohistochemical technique to localize COX-2 in colorectal carcinoma tissues. Results. Immunohistochemical staining of the colorectal cancer specimens demonstrated that COX-2 expression was localized to the carcinoma cells and was not detectable in the stromal compartment of the cancers. The COX-2 immunostaining pattern was predominantly homogenous, and perinuclear cytoplasmic within the tumors. Normal colonic epithelium adjacent to the tumor showed no staining for COX-2. The COX-2 protein was detected in 70% (42/60) of colorectal carcinoma tissues. However, no significant correlation was found between COX-2 expression and various clinicopathological parameters, including histologic grade, tumor size, depth of invasion, lymph node metastasis, distant metastasis, or stage. Furthermore, COX-2 expression did not correlate with patient survival (p=0.401). Conclusion. These results suggest that COX-2 expression may play an important role in the evolution of colon carcinogenesis. However, further studies are needed to determine the prognostic relevance of COX-2.     

Role of cyclooxygenase-2 and inducible nitric oxide synthase in pancreatic cancer

BACKGROUND AND AIM: Recently, it has been recognized that both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) produce important endogenous factors of human tumor progression. However, the clinicopathological and biological significance of the expression of COX-2 and iNOS in pancreatic cancer remains unclear. The objective of this study is to find the possible roles and clinical significance of COX-2 and iNOS expression in pancreatic cancer. METHODS: Seventy-two pancreatic adenocarcinoma tissue specimens were obtained through surgical resection. We investigated the immunohistochemical expression of COX-2 and iNOS in respect to variable clinicopathological characteristics, proliferation activity (by Ki-67 expression), apoptosis (by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling stain), and microvessel density (by CD34 expression; angiogenesis). RESULTS: Immunohistochemical investigations demonstrated immunolabeling of tumor cells with the primary antibodies, bovine anti-iNOS and anti-COX-2 antibodies. The COX-2 and iNOS positive rates were 41.7 and 66.7%, respectively. There was significant correlation between positive COX-2 and positive iNOS expression (P = 0.043). The proliferation index (Ki-67 labeling index) was higher in COX-2 positive specimens compared to COX-2 negative specimen (P = 0.015). The apoptotic index of positive iNOS expressions was significantly higher than negative expressions (P < 0.001). The expression of COX-2 and iNOS proteins did not correlate with age, sex, serum bilirubin, CA-19-9, location, size, American Joint Committee on Cancer stage, differentiation, distant metastasis, patient survival, or microvessel density. CONCLUSIONS: Although the pattern of positive expression was similar in both enzymes, the effect on tumor progression differed; iNOS expression may play a role in apoptosis of tumor cell, while COX-2 expression may contribute to tumor proliferation. However, COX-2 and iNOS expression is not related to prognosis in patients with pancreatic cancer.     

Overexpression of cyclooxygenase-2 correlates with advanced stages of colorectal cancer

OBJECTIVE: We aimed to investigate the associations of cyclooxygenase-2 (COX-2) with pathological features and survival in patients with colorectal cancer. METHODS: The expression of COX-2 was examined by immunohistochemistry in 112 primary colorectal cancers, with 64 samples from the corresponding normal mucosa and 16 metastases in the regional lymph nodes of patients with colorectal cancer. The associations of COX-2 expression with clinicopathological features, including survival, were analyzed. RESULTS: The frequency and intensity of COX-2 staining were remarkably increased from the normal samples (17%) to the primary tumors (72%) and to the metastases (100%). Expressions of COX-2 were 25%, 74%, 78%, and 67% in Dukes' A, B, C, and D tumors, respectively (p = 0.005), and positively related to proliferative activity (p = 0.003). COX-2 expressions were 80% in colonic tumors and 60% in rectal tumors (p = 0.03). The expression of COX-2 was positively related to the better differentiated tumors in the colon (p = 0.04). We were unable to find any relationship of COX-2 with patient age, sex, tumor growth pattern, apoptosis, and patient survival (p > 0.05). CONCLUSION: We found that the expression of COX-2 was upregulated from normal cells to primary tumors and to metastases, and related to proliferative activity, tumor location, Dukes' stage, and differentiation. These results further support the evidence that COX-2 may be involved in tumorigenesis and development of colorectal cancer.     

Cyclooxygenase-2 overexpression correlates with vascular endothelial growth factor expression and tumor angiogenesis in gastric cancer

Angiogenesis is a key prerequisite for the successful establishment, growth, and dissemination of tumors. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and cyclooxygenase-2 (COX-2) promotes angiogenesis by modulated production of angiogenic factors including VEGF. The current study was designed to investigate the possible roles of COX-2 and VEGF in gastric cancer angiogenesis. In this study, we conducted an immunohistochemical investigation of COX-2 and VEGF expression in 97 patients with gastric cancer. To assess tumor angiogenesis, microvessel density (MVD) was determined by CD34 immunohistochemical staining. Expression of COX-2 and VEGF in gastric cancer tissues, was demonstrated in 63.9% and 75.3% of cases, respectively. The expression of COX-2 correlated significantly with VEGF expression. High MVD was significantly associated with depth of tumor invasion and poor survival. The mean MVD value of VEGF positive tumors was 79.8 +/- 32.0 and significantly higher than that of VEGF negative tumors. The mean MVD value of COX-2 positive tumors was 77.9 +/- 29.9 and not significantly higher than that of COX-2 negative tumor. The mean value of MVD in tumors positive for both COX-2 and VEGF was significantly higher than that in tumors negative for both. However, there was no correlation between COX-2 or VEGF expression and various clinicopathological features including patient survival. These results suggest that COX-2 may play an important role in carcinogenesis by stimulating tumor angiogenesis in concert with VEGF in human gastric cancer.     

Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer.

BACKGROUND & AIMS: Recent studies have shown that cyclooxygenase (COX)-2 and its products, prostaglandins (PGs), may be involved in colorectal carcinogenesis. The aim of this study was to determine whether COX-2 expression and PGE(2) production correlate with microvessel density, vascular endothelial growth factor (VEGF) expression, and tumor metastasis in human colorectal cancer. METHODS: Tumor samples and adjacent normal mucosa were obtained from 31 surgical specimens. Immunohistochemical expression of COX-2, VEGF, and CD31 was analyzed on paraffin-embedded tissue sections. COX-2 and COX-1 proteins were determined by Western blot analysis. COX-2 and VEGF messenger RNA expressions were evaluated using Northern blot analysis. PGE(2) production was determined by specific radioimmunoassay. RESULTS: The immunohistochemical expressions of both COX-2 and VEGF were significantly correlated with microvessel density (P = 0.02 and P = 0.002, respectively). A significant correlation was found between COX-2 and VEGF expression (P = 0.004). Western analysis confirmed the up-regulation of COX-2 protein expression. COX-2 and VEGF genes were overexpressed in tumor specimens as compared with normal mucosa. PGE(2) levels were significantly higher in metastatic tumors than in nonmetastatic ones (P = 0.03). CONCLUSIONS: COX-2 is related to tumor angiogenesis in colorectal cancer. It is likely that VEGF is one of the most important mediators of the COX-2 angiogenic pathway.     

结直肠癌组织HHLA2、 TMIGD2表达及其临床病理意义

目的 探讨结直肠癌组织中人内源性逆转录病毒-H长末端重复关联蛋白2(HHLA2)、跨膜和免疫球蛋白结构域2(TMIGD2)表达及其与患者临床病理特征及预后的关系.方法 选取2016年10月至2017年10月于北京老年医院住院治疗的168例结直肠癌患者(结直肠癌组);选取结直肠癌患者相应癌旁正常组织作为对照组.采用免疫组...