Clinicopathological significance of PD-L1 expression in colorectal cancer: Impact of PD-L1 expression on pFOXO1 expression

ObjectiveThis study aimed to evaluate the clinicopathological significance of PD-L1 expression and its impact on phospho-Forkhead box O 1 (pFOXO1) expression in colorectal cancer (CRC).MethodsImmunohistochemical analysis for PD-L1 and pFOXO1 was performed on 265 human CRC tissues. PD-L1 expression was evaluated in the tumor and immune cells. The impact of PD-L1 expression on survival was investigated in relation to the pattern of pFOXO1 expression.ResultsPD-L1 was expressed in 25 (9.4%) and 41 (17.7%) patients in the tumor and immune cells of the 265 CRC tissues, respectively. PD-L1 expression in immune cells (I-PD-L1) was significantly correlated with less lymphatic invasion, lymph node metastasis, and distant metastasis and lower pT and pTNM stages. Additionally, there was a significant correlation between PD-L1 expression in tumor cells (T-PD-L1) and tumor location (right colon), but not the other clinicopathological characteristics. pFOXO1 expression was significantly lower in CRC with high I-PD-L1 expression than in CRC with low or negative I-PD-L1 expression. However, there was no significant correlation between pFOXO1 and T-PD-L1 expression in CRC. Patients with positive pFOXO1 and low or negative I-PD-L1 expression exhibited the worst survival among patients with CRC.ConclusionCollectively, our results indicate that I-PD-L1 expression was significantly correlated with favorable tumor behaviors and better survival. In addition, patients with high I-PD-L1 and low pFOXO1 expressions had a favorable prognosis than those with other I-PD-L1 and pFOXO1 expression patterns.     

转录因子FOXO4在大肠癌中的表达及意义

目的:探讨叉头样转录因子O4(FOXO4)在大肠癌组织中的表达及其临床意义。方法:选取80例大肠癌患者手术切除肿瘤及其癌旁组织标本(TNM分期:I期18例,Ⅱ期32例,Ⅲ期24例,Ⅳ期6例),应用免疫组织化学染色方法检测FOXO4在大肠癌和癌旁组织的表达情况,并分析其与患者临床病理特征的关系。结果:FOXO4在大肠癌组织中的阳性表达率为47.50%(38/80),明显低于在癌旁组织91.25%(73/80)的表达率(P<0.01)。在肿瘤组织中FOXO4表达水平在患者年龄、性别,肿瘤大小和侵润深度之间的差异无统计学意义(P>0.05);但与肿瘤分化程度、分期和淋巴结转移之间差异有统计学意义(P<0.05)。结论:FOXO4在大肠癌中表达明显降低或缺失,提示其可能在大肠癌的发生、发展过程中起抑癌基因的作用。     

Prognostic significance of glucose-related protein 94 in colorectal cancer

AimsThe expression of glucose-related protein 94 (GRP94), a member of the heat shock protein 90 family, was correlated with a variety of clinicopathological factors and patient survival in a large colorectal cancer (CRC) cohort. We aimed to elucidate the role of GRP94 in the prognosis of CRC patients.MethodsTissue microarray blocks were generated from 709 CRC samples and immunohistochemically stained for GRP94.ResultsOf the 709 tumours, 164 (23.1%) and 545 (76.9%) were classified in the low and high expression groups, respectively. GRP94 expression was high in CRC cases with larger tumours (p = 0.005) and advanced pT stage (p = 0.021). GRP94 expression was higher in females than males (p = 0.024). In univariate and multivariate survival analyses, high GRP94 expression was unexpectedly associated with better overall survival in CRC patients younger than 65 years of age (p = 0.001)ConclusionOur conflicting results indicate that GRP94 has the ability to switch between oncogenic and tumour-suppressive roles depending on the conditions and microenvironment of the tumour cells. Furthermore, GRP94 could be a candidate biomarker to predict better prognosis in CRC patients.     

人结直肠癌组织中表皮生长因子受体1与Fascin-1蛋白表达的相关性及其临床意义

目的 探讨人结直肠癌组织中表皮生长因子受体1(EGFR)与Fascin-1蛋白表达的关系及其临床意义。方法 回顾性收集2008年1月-2010年12月东阳市人民医院病理科结直肠癌石蜡标本258例和同时切除的正常结直肠组织石蜡标本72例。采用免疫组织化学EnVision法检测并比较直肠癌组织和正常结直肠组织中EGFR和Fascin-1蛋白的表达;分析结直肠癌中Fascin-1蛋白表达与结直肠癌患者临床病理特征、EGFR的关系,以及EGFR和Fascin-1蛋白的表达与患者的预后生存情况的关系。结果 (1)结直肠癌组织中Fascin-1蛋白的阳性率为38.0%(98/258),高于正常结直肠组织的阳性率0.0%(0/72),差异有统计学意义(χ²=38.901,P＜0.01)。(2)女性、结肠及低分化的结直肠癌患者中Fascin-1蛋白的阳性率高于男性、直肠及高-中分化患者(χ²=4.256、20.085、8.471,P值均＜0.05)。(3)在EGFR阳性结直肠癌患者的Fascin-1蛋白阳性表达率(42.9%,91/212)较EGFR阴性病例(15.2%,7/46)高,差异有统计学意义(χ²=12.318, P＜0.01);Spearman相关分析显示,结直肠癌组织中EGFR和Fascin-1蛋白表达呈正相关(r_s=0.219,P＜0.01)。(4)194例获得随访的结直肠癌患者5年总生存率为73.2%(142/194),5年无复发生存率为65.5%(127/194)。其中EGFR和Fascin-1均阳性患者的5年平均总生存期及5年总生存率(47.8个月、64.7%)低于非均阳性患者(54.4个月、77.8%),差异有统计学意义(χ²=5.039, P＜0.05)。结论 结直肠癌中EGFR与Fascin-1蛋白的表达呈正相关,二者同时表达与患者预后不良有关。     

Expression of TUSC3 and its prognostic significance in colorectal cancer

Background

Colorectal cancer (CRC) is one of the most common cancers worldwide. Tumor suppressor candidate 3 (TUSC3) has been reported be associated with embryogenesis and metabolism. The aim of this study is to investigate the expression of TUSC3 in CRC tissues, and to evaluate the clinical pathological characters and prognostic significance.

Cytoplasmic Pin1 expression is correlated with poor prognosis in colorectal cancer

Objective

The aim of this study was to determine the clinicopathological significance and prognostic role of Pin1 expression and subcellular localization in colorectal cancer (CRC).

The clinicopathological significance of SIRT1 expression in colon cancer: An immunohistochemical study and meta-analysis

Objective

The aim of this study was to determine the clinicopathological significance and potential prognostic role of SIRT1 expression in colorectal cancer (CRC) using immunohistochemistry and meta-analysis.

结直肠腺瘤及腺癌组织中FOXO1表达及其临床意义

目的检测结直肠腺瘤及腺癌组织中转录因子FOXO1的表达,在组织学水平上初步探讨FOXO1在结直肠腺瘤癌变过程中的作用及其与临床病理特征的关系。方法采用Western blot法免疫组化SP两步法检测146例结直肠腺瘤、48例结直肠腺癌及48例癌旁组织中FOXO1蛋白的表达水平。结果 FOXO1在结直肠腺瘤及腺癌组织中的表达明显低于正常组织,组间比较差异有统计学意义(P0.01)。结直肠腺瘤组织中FOXO1表达与肿物大小相关,腺癌组织中FOXO1表达与肿瘤分化程度相关。结论 FOXO1在人类肠道癌前病变(腺瘤)及腺癌组织细胞核表达减少和缺失,可能是导致结肠腺癌发病的机制之一,其在结直肠癌的发生、发展过程中起抑癌基因的作用,有望成为下一个潜在的临床治疗靶点。     

Peroxiredoxin 1 promoted tumor metastasis and angiogenesis in colorectal cancer

Peroxiredoxin1 (Prdx1) is a member of the PrdxS family, and it regulates cellular signaling and differentiation. The role of Prdx1in colorectal cancer (CRC) remains unclear. In this study, we investigated the relevance of Prdx1 in the metastasis and angiogenesis of CRC. The expression of Prdx1 in 60 cases human CRC tissues was detected through immunohistochemistry. The tumors that highly expressed Prdx1 (42/60) exhibited higher tumor grade and lymph node metastasis than those with low expression of Prdx1 (18/60) (p?<?0.05). Kaplan–Meier survival analysis showed that the survival time of thePrdx1-positive group was shorter than that of thePrdx1-negative group (p?=?0.046).Moreover, a statistically significant correlation was observed between the Prdx1 expression and microvessel density (p?=?0.004). Transwell migration assay revealed that Prdx1 was down-regulated in the CRC cell line HCT116, thereby suppressing the invasion and migration capacities of tumor cells, whereas Prdx1was up-regulated in HT29 cells, thereby increasing the invasion and migration capacities of tumor cells. The tube formation capacity of human umbilical vein endothelial cells cultured in 3D medium was increased after conditioned medium from overexpressed Prdx1cancer cells was added relative to that when down-regulated Prdx1 cell medium was added (p?<?0.05). In addition, up-regulated Prdx1 increased the protein expression of MMP2, MMP9, and VEGFA. These data suggested that Prdx1 expression predicted poor prognosis by regulating the tumor metastasis and angiogenesis of CRC. Therefore, Prdx1 may serve as a potential therapeutic target.     

转录因子RUNX1在结直肠癌中的表达及作用

目的应用在线公共数据库分析转录因子RUNX1的表达,研究其表达的临床意义。方法通过Oncomine、GEPIA公共数据库分析结直肠癌中RUNX1基因mRNA的表达情况,通过HPA(Human Protein Atlas)数据库分析RUNX1基因的蛋白表达情况,通过GEPIA分析RUNX1表达与肿瘤病理分期的关系以及RUNX1表达与患者生存期的关系。结果RUNX1 mRNA和蛋白在结直肠癌表达水平上调,与结直肠癌分期无显著相关。RUNX1表达与结肠癌(COAD)患者总体生存率(OS)和无病生存率(DFS)显著相关,其表达量越高,患者生存期越短;但与直肠癌(READ)患者OS和DFS无显著相关。结论RUNX1参与结肠癌的发病机制,是治疗结肠癌的潜在靶点。     

Clinicopathological significance of ERCC1 expression in breast cancer

The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy in different types of cancer. The aim of the present study was to evaluate the clinicopathological significance of ERCC1 expression in breast cancer patients. We analyzed the immunohistochemical expression of ERCC1 in a tissue microarray from 135 primary breast carcinomas and correlated the immunohistochemical findings with clinicopathological factors and outcome data. ERCC1 expression analysis was available for 109 cases. In this group, 58 (53.2%) were positive for ERCC1. ERCC1-positive expression was correlated with smaller tumor size (P = 0.007) and with positivity for estrogen receptor (P = 0.040), but no correlation was found with other clinicopathological features. Although not statistically significant, triple negative breast cancers were more frequently negative for ERCC1 (61.5% of the cases) compared to the non-triple negative breast cancer cases (41.5%). In conclusion, ERCC1 expression correlated significantly with favorable prognostic factors, such as smaller tumor size and ER-positivity, suggesting a possible role for ERCC1 as a predictive and/or prognostic marker in breast cancer.     

Gab2在结直肠癌组织中的表达及其意义

目的:探讨Gab2在结直肠癌组织中的表达及其意义。方法:应用免疫组化方法检测78例结直肠癌及46例癌旁正常组织中Gab2的表达水平,并结合临床病理学资料进行统计学分析,Western blot方法检测10对结直肠癌组织及相对应的癌旁正常组织中Gab2的表达状况。结果:免疫组化检测结果显示78例结直肠癌组织中Gab2蛋白表达阳性率为53.85%,而癌旁正常组织中Gab2蛋白多不表达或弱表达,两组结果比较差异有显著性(P0.001);Gab2蛋白在结直肠癌中的表达与肿瘤TNM分期及有无淋巴结转移呈正相关(P0.05),与肿瘤大小、分化程度无明显相关性(P0.05);Western blot检测结果显示结直肠癌组织中Gab2蛋白表达显著高于相对应的癌旁正常组织(P0.05)。结论:Gab2在结直肠癌组织中过表达,可能在结直肠癌的发生发展中起重要作用。     

Differential expression of alpha-methylacyl-coenzyme A racemase in colorectal carcinoma bears clinical and pathologic significance

alpha-methylacyl-coenzyme A racemase (AMACR) is a recently discovered biomarker that is shown to be overexpressed in some prostatic carcinomas and associated with prostatic cancer progression. Given that AMACR plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids from red meat and dairy products, and that consumption of red meat may increase risk of developing colon cancer as suggested by epidemiological studies, it is plausible to explore the function of AMACR in colorectal carcinoma. A few previous studies have indeed observed overexpression of AMACR in 45% to 69% of the colorectal carcinomas. However, the clinical and pathologic characteristics of such AMACR expressers have not been investigated. In this study, the immunohistochemical expression pattern of AMACR of 163 patients with primary colorectal carcinoma treated primarily with surgical resection was analyzed and correlated with tumor pathologic features (tumor location, histologic type, grade, pathologic stage, lymph node and distant metastasis) and patient outcome (disease-specific survival). The results showed variable positive staining for AMACR in 123 (75%) of 163 tumors, and moderate to strong staining in 63 (39%) of 163. Lack of staining or low-intensity staining appeared to correlate significantly with mucinous histology (P < .001), poor tumor differentiation (P = .021), and presence of lymphovascular invasion (P = .032). Patients whose tumors showed lack of staining or low-intensity staining also had a significantly worse 5-year disease-specific survival (P < .012), as did patients whose tumors had lymphovascular invasion, or were of high American Joint Committee on Cancer (AJCC) stage. On multivariate analysis, AMACR staining and AJCC staging remained independent predictors for patient outcome. Thus, our data suggest that AMACR expression in colorectal carcinoma correlates with certain tumor pathologic characteristics (histologic type, differentiation, and lymphovascular invasion) and patient outcome. Additional confirmatory studies are needed to establish the significance of AMACR as a prognostic marker for colorectal carcinoma. Further investigation on interaction between AMACR and other known colorectal cancer development pathways may provide new insights on colorectal carcinogenesis.     

Clinicopathological significance of maspin expression in breast cancer

Maspin is a unique serine proteinase inhibitor that has tumor suppressor activity. It has been reported that maspin is expressed in normal human mammary epithelial cells and it is down-regulated during the progression of cancer. However, to date, there is very limited data on the clinical significance of maspin expression in human breast cancer. In this study, maspin expression was assessed immunohistochemically from 80 invasive ductal carcinoma (IDC) specimens of the breast. Also, maspin expression was compared with the clinicopathological factors (age, grade, tumor size and lymph node status), the expression of estrogen receptor (ER), progesterone receptor (PR) and p53, DNA ploidy and the overall survival in an attempt to assess its prognostic value. The maspin expression was positive in 25 IDC cases (31.3%). The maspin expression in IDC was significantly correlated with a higher histologic grade, a larger tumor size, a positive p53 status and shorter survival. There was an inverse association with maspin expression and the PR status. These findings suggest that maspin expression is not down-regulated with the progression of cancer and maspin expression may be associated with a poor prognosis. The immunohistochemical detection of maspin in breast cancers may be helpful for predicting an aggressive phenotype.