Correlation of caveolin-1 expression with microlymphatic vessel density in colorectal adenocarcinoma tissues and its correlation with prognosis

Objective: To study the expression of caveolin-1 in colorectal adenocarcinoma tissues and its correlation with microlymphatic vessel density(LMVD), and to investigate the clinical pathological prognostic significance of caveolin-1 and LMVD in patients with colorectal cancer. Methods: The expression of caveolin-1 and LMVD in 45 specimens of normal colorectal tissues, and 90 specimens of colorectal adenocarcinoma tissues were detected by immunohistochemistry technique. The correlation between their expression and the clinicopathologic features was analyzed. Muhivariable Cox regression was used to analyze the association between the laboratory indices and overall survival time. Results: The positive rates of caveolin-1 in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues(P0.01). LMVD in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues(P0.01). Mean LMVD in group with caveolin-1 positive was significantly higher than in that with caveolin-1 negative. The median survival time was 26.7 months. Cox regression analysis showed that the caveolin-1 expression, invation depth, lymph nodemetastasis, TNM stage, liver metastasis and LMVD were independent risk factors of overall survival time of patients with colorectal carcinoma. Conclusions: Caveolin-1 may contribute to the lymphangiogenesis in the tumor. During the occurrence and development of colorectal adenocarcinoma, there is a close relationship between the expression of caveolin-1 and lymphatic microvessel of tumor. Caveolin-1 expression and microlymphatic vessel density are significant prognostic value of colorectal carcinoma.     

The association of the expression level of protein tyrosine phosphatase PRL-3 protein with liver metastasis and prognosis of patients with colorectal cancer

PURPOSE: To investigate PRL-3 protein expression in normal colorectal epithelia and colorectal cancers with monoclonal antibody (MAb) against PRL-3. METHODS: MAb against PRL-3 was prepared with the hybridoma technique, and its specificity was confirmed with ELISA and Western blotting assays. The expression of PRL-3 protein in normal colorectal epithelia and colorectal cancers was examined by immunohistochemistry assay. Logistic regression and survival analysis were performed to determine the clinical significance of PRL-3 expression. RESULTS: MAb 3B6 against PRL-3 was obtained and showed high specificity. PRL-3 protein was expressed in two of 28 (7.1%) normal colorectal epithelia, 21 of 88 (23.9%) primary colorectal cancers, 22 of 41 (53.7%) metastatic lymph nodes and eight of 12 (66.7%) liver metastases, respectively. The PRL-3 expression rates of metastases were significantly higher than those of primary colorectal cancers and normal colorectal epithelia (P < 0.05). PRL-3 expression was significantly associated with the liver metastasis of colorectal cancer (P = 0.004) and tended to shorten survival time (P = 0.0145). CONCLUSIONS: This is the first study demonstrating that PRL-3 is a potential marker for liver metastasis of colorectal cancer and negatively influences the prognosis of colorectal cancer patients.     

15-LOX-1蛋白在大肠癌中的表达及临床意义

目的探讨15-LOX-1蛋白表达与大肠癌临床病理因素和患者预后的关系,并探索其可能的作用机制。方法采用免疫组化SP法,检测15-LOX-1蛋白在103例大肠癌组织、56例大肠癌癌旁正常组织中的表达,结合患者的临床病理因素、预后情况及大肠癌组织中其他与侵袭转移相关的指标进行分析。结果 15-LOX-1蛋白在大肠癌组织中的阳性表达率显著低于大肠癌癌旁正常组织(P<0.05);15-LOX-1蛋白的表达与大肠癌的组织病理类型、淋巴结转移、其他器官侵袭转移以及Dukes分期密切相关(P<0.05),病理分化程度低、Dukes分期晚以及有淋巴结或其他器官侵袭转移者肠癌组织中15-LOX-1蛋白表达水平降低;大肠癌组织中15-LOX-1阳性表达患者1年、3年、5年生存率及中位生存时间明显高于15-LOX-1阴性表达患者(P<0.05),多因素COX回归分析结果提示15-LOX-1表达水平、患者年龄及手术时有无淋巴结转移可以作为评估大肠癌患者预后的独立因素(P<0.05);大肠癌中15-LOX-1与VEGF、MMP-2、MMP-7的表达均呈负相关(P<0.05)。结论 15-LOX-1对大肠癌具有抑癌作用,对反映大肠癌生物学行为和判断预后有重要意义。     

High level of ezrin expression in colorectal cancer tissues is closely related to tumor malignancy

AIM： To investigate the ezrin expression in normal colorectal mucosa and colorectal cancer tissues, and study the correlation between ezrin expression in colorectal cancer tissues and tumor invasion and metastasis. METHODS： Eighty paraffin-embedded cancer tissue samples were selected from primary colorectal adenocarcinoma. Twenty-eight patients had well- differentiated, 22 had moderately differentiated and 30 had poorly differentiated adenocarcinoma. Forty-five patients and 35 patients had lymph node metastasis. Forty-five patients were of Dukes A to B stage, and 35 were of C to D stage. Another 22 paraffin-embedded tissue blocks of normal colorectal epithelium （〉 5 cm away from the edge of the tumor） were selected as the control group. All patients with colorectal cancer were treated surgically and diagnosed histologically, without preoperative chemotherapy or radiotherapy. The immunohistochemistry was used to detect the ezrin expression in paraffin-embedded normal colorectal mucosa tissues and colorectal cancer tissue samples. RESULTS： Ezrin expression in colorectal cancer was significantly higher than in normal colorectal mucosa （75.00% vs 9.09%, P 〈 0.01）, and there was a close relationship between ezrin expression and the degree of tumor differentiation, lymph node metastasis and Dukes stage （88.46% vs 50.00%, P 〈 0.01; 94.28% vs 51.11%, P 〈 0.01; 94.28% vs 51.11%, P 〈 0.01）. CONCLUSION： Ezrin expression is obviously higher in colorectal cancer tissues than in normal colorectal mucosa tissues, and the high level of ezrin expression is closely related to the colorectal cancer invasion and metastasis process.     

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.     

TSPAN1 protein expression： A significant prognostic indicator for patients with colorectal adenocarcinoma

AIM： To determine if TSPAN1 overexpression is associated with clinicopathological and prognostic factors in human colorectal adenocarcinoma.METHODS： Total RNA was extracted in 20 human adenocarcinoma tissues for TSPAN1 mRNA assay by RT-PCR. Eighty-eight specimens of human colorectal adenocarcinoma were surgically removed. TSPAN1 protein levels in cancer tissues were determined by immunohistochemistry using a polyclonal antibody against self-prepared TSPAN1. The correlation between TSPAN1 expression and the clinicopathological factors and the overall survival rate was analyzed by univariate and multivariate assay.RESULTS： TSPAN1 mRNA was detected in 90.0%（18/20） of cancerous tissues. The light density of TSPAN1 mRNA expression levels was 0.89 ± 0.30 in adenocarcinoma by gel-image system. TSPAN1 protein expression was detected in 78.41% （69/88） and weakly expressed in 40% normal colorectal tissues.There were significant differences between colorectal adenocarcinoma and normal control epithelium （P 〈 0.05）. TSPAN1 protein expression in colorectal cancerous tissue was significantly correlated with the histological grade, cell expression PCNA, lymph nodal metastasis and TNM staging of the disease. Patients with TSPAN1 protein overexpression had a significantly shorter survival period than that in patients with TSPAN1 protein negative or weak expression,respectively （P 〈 0.05）. Furthermore, by multivariate analysis, TSPAN1 protein expression demonstrated an independent prognostic factor for human colorectal cancers （P 〈 0.05, relative risk 0.755; 95% confidence interval 0.302-1.208）.CONCLUSION： The expression of TSPAN1 gene is increased in colorectal carcinoma, suggesting that TSPAN1 might serve as an independent prognostic factor for the colorectal adenocarcinoma patients.     

NF-κB及其抑制蛋白I-κBα与大肠癌侵袭和转移的相关性

目的 探讨NF-κB和I-κBα在大肠癌中的表达特点、相互关系及其与大肠癌进展的相关性.方法 免疫组化和Western印迹方法检测48例大肠癌患者手术切除的癌组织以及配对的癌旁正常组织标本中NF-κB,I-κBα和p-IκBα的表达情况,分析这3种蛋白的表达与大肠癌侵袭和转移的相关性.结果 大肠癌组织中NF-κB的表达水平明显高于正常组织(P＜0.01),且随着肿瘤Dukes分期的进展,NF-κB的表达水平呈逐渐升高趋势.大肠癌组织中I-κBα的表达水平明显低于正常组织(P＜0.01),且随着肿瘤Dukes分期的进展,I-κBα的表达水平呈逐渐降低趋势,同时,I-κBα的磷酸化(p-IκBα)水平逐渐升高.结论 在大肠癌组织中I-κBα的磷酸化降解与NF-κB表达升高有助于肿瘤的进展和不良预后.     

Ornithine decarboxylase gene is overexpressed in colorectal carcinoma

AIM: To investigate the ornithine decarboxylase (ODC) gene expression in colorectal carcinoma, ODC mRNA was assayed by RT-PCR and ODC protein was detected by a monoclonal antibody against fusion of human colon ODC prepared by hybridoma technology. METHODS: Total RNA was extracted from human colorectal cancer tissues and their normal counterpart tissues. ODC mRNA levels were examined by RT-PCR. ODC genes amplified from RT-PCR were cloned into a prokaryotic vector pQE-30. The expressed proteins were purified by chromatography. Anti-ODC mAb was prepared with classical hybridoma techniques and used to determine the ODC expression in colon cancer tissues by immunohistochemical and Western blotting assay. RESULTS: A cell line, which could steadily secrete anti-ODC mAb, was selected through subcloning four times. Western blotting reconfirmed the mAb and ELISA showed that its subtype was IgG2a. RT-PCR showed that the ODC mRNA level increased greatly in colon cancer tissues (P<0.01). Immunohistochemical staining showed that colorectal carcinoma cells expressed a significantly higher level of ODC than normal colorectal mucosa (98.6±1.03% vs5.26±5%,P<0.01). CONCLUSION: ODC gene overexpression is significantly related to human colorectal carcinoma. ODC gene expression may be a marker for the gene diagnosis and therapy of colorectal carcinoma.     

Syndecan-1在结直肠腺瘤和腺癌中的表达变化及其意义

Syndecan-1是一种由硫酸乙酰肝素链和硫酸软骨素链修饰的I型跨膜蛋白多糖，主要表达于上皮细胞表面，与肿瘤的多种生物学行为关系密切。目的：研究Syndecan-1在结直肠腺瘤和腺癌中的表达，探讨其与结直肠腺瘤和腺癌发生的关系。方法：分别采用逆转录聚合酶链反应（RT-PCR）和免疫组化染色检测56例结直肠腺瘤、42例腺癌和20例正常结肠组织中Syndecan．1mRNA和蛋白表达，并分析其与结直肠腺癌临床病理特征的关系。结果：RT-PCR和免疫组化染色结果显示Syndecan-1mRNA和蛋白在重度异型增生腺瘤和腺癌中的表达显著低于正常结肠组织和轻、中度异型增生腺瘤（P〈0．05），正常结肠组织与轻、中度异型增生腺瘤之间以及重度异型增生腺瘤与腺癌之间其表达无明显差异。Syndecan-1mRNA和蛋白表达与腺癌分化程度、浸润深度、淋巴结转移、远处转移以及TNM分期相关（P〈0．05），与性别、年龄以及是否合并结直肠腺瘤无关。结论：随着结直肠腺癌恶性程度的增加，Syndecan-1表达显著降低。Syndecan-1介导的细胞间黏附破坏在结直肠癌的致癌机制中可能起关键作用。     

ETS2在结直肠癌组织中的表达及临床意义

目的探讨转录因子ETS2（E-twenty six 2）在结直肠癌组织中的表达情况,分析其与结直肠癌患者临床病理参数之间的关系,并评估其临床预后价值。 方法收集新鲜的结直肠癌、癌旁和相应正常组织,以及结直肠癌和癌旁组织的石蜡标本,采用实时荧光定量PCR法检测组织中ETS2 mRNA的表达,免疫组化检测石蜡切片中ETS2蛋白的表达。 结果结直肠癌组织中ETS2 mRNA的表达明显高于癌旁组织和正常组织（P<0.001）,而癌旁组织和正常组织中的ETS2 mRNA表达量差异无统计学意义（P>0.05）。免疫组化结果显示ETS2在52.07%（63/121）的结直肠癌中表达,而仅在13.04%（6/46）的癌旁组织中表达,两者比较差异有统计学意义（P<0.05）。ETS2表达与肿瘤分化程度、浸润深度、淋巴结转移以及MMR状态有关（P<0.05）。ETS2表达与结直肠癌患者术后无进展生存有关（P<0.001）。采用COX多因素回归分析发现,ETS2表达（HR：0.461,95%CI：0.271~0.683,P=0.003）和浸润深度（HR：0.352,95%CI：0.113~0.769,P=0.015）是结直肠癌患者术后无进展生存的独立预后因子。 结论与癌旁组织相比,ETS2在结直肠癌组织中的转录和翻译水平都过表达,ETS2是预测结直肠癌患者术后无进展生存的潜在标记物。     

Expression of Interleukin-11 and Interleukin-11 receptor α in human colorectal adenocarcinoma; lmmunohistochemical analyses and correlation with clinicopathological factors

AIM: There is strong evidence that interleukin-11 (IL-11) is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11 receptor (IL-11R) has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma. METHODS: To elucidate the involvement of IL-11 and IL-11Ra in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry and Western blotting. RESULTS: Among 115 cases of adenocarcinoma, 100 cases (87.0%) showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases (75.6%) were positive for the IL-11Ra. Six cases (54.5%) and four cases (36.4%) of 11 adenomas were positive for IL-11 and IL-11Ra, respectively. The expression of IL-11Ra correlated with the histological differentiation (P = 0.033503), the depth of tumor invasion (P = 0.006395), Dukes'classification (P = 0.015648) and lymphatic invasion (P = 0.003865). However, the expression of IL-11Ra was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Ra proteins. CONCLUSION: IL-11 and IL-11Ra are highly expressed in human colorectal adenocarcinoma and the IL-11Ra expression is correlated with clinicopathological factors. These findings suggest that the expression of IL-11Ra is an important factor for the invasion of human colorectal adenocarcinoma.     

Expression of Interleukin-11 and Interleukin-11 receptor in human colorectal adenocarcinoma; Immunohistochemical analyses and correlation with clinicopathological factors

AIM: There is strong evidence that interleukin-11 (IL-11)is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11receptor (IL-11R) has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma.METHODS: To elucidate the involvement of IL-11 and IL-11Rα in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry and Western blotting.RESULTS: Among 115 cases of adenocarcinoma, 100cases (87.0%) showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases (75.6%)were positive for the IL-11Rα. Six cases (54.5%) and four cases (36.4%) of 11 adenomas were positive for IL-11 and IL-11Rα, respectively. The expression of IL-11Rα correlated with the histological differentiation (P =0.033503), the depth of tumor invasion (P= 0.006395),Dukes classification (P= 0.015648) and lymphatic invasion (P=0.003865). However, the expression of IL-11Rα was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Rαproteins.CONCLUSION: IL-11 and IL-11Rα are highly expressed in human colorectal adenocarcinoma and the IL-11Rα expression is correlated with clinicopathological factors.These findings suggest that the expression of IL-11Rα is an important factor for the invasion of human colorectal adenocarcinoma.     

Slug和E-cadherin在结直肠癌组织中的表达及临床意义

目的探讨Slug和E-cadherin在结直肠癌组织中的表达及预后意义。方法应用免疫组化SP法检测65例结直肠癌组织,25例癌旁正常结直肠组织中Slug和E-cadherin的表达,分析两者表达水平与临床病理特征及患者预后的关系。结果 Slug在结直肠癌组织中异常表达率为47.1%,而在正常结直肠组织中表达率为12%,差异有统计学意义(P<0.01);E-cadherin在结直肠癌组织中异常表达率为55.4%,而在正常结直肠组织中表达率为8%,差异有统计学意义(P<0.01);两者阳性表达率与肿瘤浸润深度、分化程度、淋巴结转移、Dukes分期相关性均有统计学意义(P<0.05)。Slug、E-cadherin、淋巴结转移、Dukes分期可成为影响结直肠癌预后的独立因素(P<0.05)。结论 Slug和E-cadherin的表达异常可能与结直肠癌的发生发展、转移相关并可作为评价结直肠癌生物学行为和预后的重要指标。     

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...     

CCL7 and CCL21 overexpression in gastric cancer is associated with lymph node metastasis and poor prognosis

AIM: To investigate how a complex network of CC chemokine ligands (CCLs) and their receptors influence the progression of tumor and metastasis.METHODS: In the present study, we used immunohistochemistry to examine the expression of CCL7, CCL8 and CCL21 in 194 gastric cancer samples and adjacent normal tissues. We analyzed their correlation with tumor metastasis, clinicopathologic parameters and clinical outcome.RESULTS: We found that the higher expression of CCL7 and CCL21 in cancer tissues than in normal tissues was significantly correlated with advanced depth of wall invasion, lymph node metastasis and higher tumor node metastasis stage. Moreover, Kaplan-Meier survival analysis revealed that CCL7 and CCL21 overexpression in cancer tissues was correlated with poor prognosis.CONCLUSION: These results suggest that overexpression of these two CC chemokine ligands is associated with tumor metastasis and serves as a prognostic factor in patients with gastric cancer.     

Functional expression of HGF and its receptor in human colorectal cancer

BACKGROUND: Hepatocyte growth factor (HGF) stimulates proliferation, migration and morphogenesis of epithelial cells by specific binding to its receptor c-met. Overexpression of HGF or c-met has been reported for human gastric or pancreatic cancer. In colorectal cancer overexpression of c-met but not HGF has been shown. However, elevated HGF serum levels have been detected in colorectal cancer patients. Therefore, the present study was performed to investigate expression patterns of both c-met and HGF in colorectal cancers and metastasis in comparison to normal mucosa. Furthermore, the mitogenic actions of HGF on colorectal cancer cells were studied in vitro. METHODS: Expression of c-met and HGF were analyzed by RT-PCR and Western blotting and localized in the tissues utilizing immunohistochemistry. Mitogenic effects of HGF were determined in four human colon cancer cell lines by (3)H-thymidine incorporation studies. RESULTS: C-met and HGF mRNA were detectable in 60% of the normal specimen, but in the majority of cancer samples, and in just 33% of the liver metastasis. In cancer samples a coexpression of c-met and HGF was detected in 77% of the specimens. The extent of protein expression of receptor and ligand correlated with the mRNA expression. Moreover, c-met protein expression was increased 2- to 3-fold in colorectal cancers. C-met was detected in cells of epithelial origin, whereas HGF was expressed by mesenchymal cells. In vitro, HGF significantly stimulated cell growth in all four cell lines. CONCLUSION: Overexpression of c-met protein in colorectal cancers is combined with an expression of HGF in the majority of cases suggesting a paracrine manner of growth enhancement, while only a weak expression of c-met or HGF was detected in metastatic tissues.