NDRG2在上皮性卵巢癌中的表达及与预后的关系

目的:探讨NDRG2在上皮性卵巢癌中的表达及其与预后的关系。方法:收集新鲜的上皮性卵巢癌和正常卵巢组织各15例,采用real-time PCR检测和比较其NDRG2 m RNA的表达。收集上皮性卵巢癌病理切片96例进行免疫组化检测其NDRG2蛋白的表达,并收集患者的临床病理资料,随访患者的生存情况,分析NDRG2蛋白的表达与上皮性卵巢癌患者临床病理特征和预后的关系。结果:上皮性卵巢癌组织中NDRG2 mRNA和蛋白的表达均显著低于正常卵巢组织(P0.05)。NDRG2在上皮性卵巢癌组织中的表达随着上皮性卵巢癌病理分期的升高而降低,而且其表达降低和患者不良预后显著相关(P=0.002),但其表达和不同上皮性卵巢癌的病理类型、分化程度以及年龄均无明显相关性。去除手术病理分期的影响,NDRG2表达下调和肿瘤细胞减灭术的满意程度以及术后规范化疗是三个影响上皮性卵巢癌预后的重要因素。结论:NDRG2在上皮性卵巢癌中的表达下降,并与患者的不良预后呈显著正相关。     

CIAPIN1 nuclear accumulation predicts poor clinical outcome in epithelial ovarian cancer

ABSTRACT: BACKGROUND: Epithelial ovarian cancer (EOC) is an aggressive disease with poor prognosis. The expression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) correlates with the malignant progression of several cancers. However, the relationship between the subcellular localization of CIAPIN1 and clinical characteristics in EOC remains unclear. METHODS: Immunohistochemistry was performed to detect CIAPIN1 expression in 108 EOC tissues. CIAPIN1 expressions in eight fresh EOC tissues were detected by Western blotting. The relationship between CIAPIN1 subcellular expression and patients? clinicopathological features, including prognosis, was evaluated. Immunohistochemistry and immunofluorescence were employed to assess the CIAPIN1 subcellular localization in the EOC cell lines A2780 and HO8910. In addition, all patients were followed up to assess the prognostic value of CIAPIN1 in patients with EOC. RESULTS: CIAPIN1 is highly expressed in EOC, but is present at low levels in paired non-cancerous ovarian epithelial tissues. The results of Western blotting were in accordance with the immunohistochemical results. Poor differentiation of the tumors and EOC cell lines correlated with higher levels of CIAPIN1 nuclear expression. CIAPIN1 nuclear expression significantly correlated with the Federation International of Gynecology and Obstetrics (FIGO) stage and histological differentiation (     

卵巢癌患者血清HB-EGF、TK1、GDF15水平与临床病理特征和预后的关系

摘要 目的：研究卵巢癌患者血清肝素结合性表皮生长因子（HB-EGF）、胸苷激酶1(TK1)、生长分化因子15(GDF15)水平与临床病理特征和预后的关系。方法：利用酶联免疫吸附试验（ELISA）检测94例卵巢癌患者和60例健康体检志愿者的血清HB-EGF、TK1、GDF15水平。Pearson相关分析卵巢癌患者血清HB-EGF、TK1、GDF15三者的相关性。分析卵巢癌患者血清HB-EGF、TK1、GDF15水平与临床病理特征的关系。Kaplan-Meier生存分析不同血清HB-EGF、TK1、GDF15水平的卵巢癌患者的生存率差异。单因素及多因素COX回归分析影响卵巢癌患者生存预后的因素。结果：与健康对照组相比,卵巢癌组患者血清HB-EGF、TK1、GDF15水平明显较高（均P<0.05）。卵巢癌组患者血清HB-EGF与TK1、GDF15水平呈正相关,TK1与GDF15水平呈正相关（均P<0.05）。卵巢癌患者血清HB-EGF、TK1、GDF15水平与FIGO分期、分化程度有关（均P<0.05）。血清HB-EGF、TK1、GDF15高水平的卵巢癌患者3年总体生存率分别低于低水平患者（P<0.05）。血清HB-EGF、TK1、GDF15高水平、FIGO分期为Ⅲ期及低分化程度是影响卵巢癌患者预后的独立危险因素。结论：卵巢癌患者血清中HB-EGF、TK1、GDF15水平升高,三者水平与卵巢癌肿瘤FIGO分期、肿瘤分化程度有关,检测血清HB-EGF、TK1、GDF15水平有助于评估卵巢癌患者的预后。     

IGF1R Axis Inhibition Restores Dendritic Cell Antitumor Response in Ovarian Cancer

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. The insulin-like growth factor (IGF) system plays a key role in regulating growth and invasiveness in several malignancies, including ovarian cancer. IGF1R targeting showed antiproliferative activity of EOC cells. However, clinical studies failed to show significant benefit. EOC cells suppress antitumor immune responses by inducing dendritic cell (DC) dysfunction. The IGF1 axis can regulate DC maturation.The current study evaluated involvement of the IGF1 axis in DC differentiation in EOC. Studies were conducted on EOC and on a human monocyte cell line. Tissue microarray analysis (TMA) was performed on 36 paraffin blocks from EOC patients. Expression of IGF1R, p53, Ki67, BRCA1, and DC markers was evaluated using immunohistochemistry. Co-culture of EOC cells with DC pretreated with IGF1R inhibitor blocked cancer cell migration. TMA demonstrated higher rate of IGF1R protein expression in patients with advanced (76.9%) as compared to early (40%) EOC. A negative correlation between IGF1R protein expression and the CD1c marker was found. These findings provide evidence that IGF1R axis inhibition could be a therapeutic strategy for ovarian cancer by restoring DC-mediated antitumor immunity.     

Application of L-EDA in metabonomics data handling: global metabolite profiling and potential biomarker discovery of epithelial ovarian cancer prognosis

Solution capacity limited estimation of distribution algorithm (L-EDA) is proposed and applied to ovarian cancer prognosis biomarker discovery to expatiate on its potential in metabonomics studies. Sera from healthy women, epithelial ovarian cancer (EOC), recurrent EOC and non-recurrent EOC patients were analyzed by liquid chromatography-mass spectrometry. The metabolite data were processed by L-EDA to discover potential EOC prognosis biomarkers. After L-EDA filtration, 78 out of 714 variables were selected, and the relationships among four groups were visualized by principle component analysis, it was observed that with the L-EDA filtered variables, non-recurrent EOC and recurrent EOC groups could be separated, which was not possible with the initial data. Five metabolites (six variables) with P?<?0.05 in Wilcoxon test were discovered as potential EOC prognosis biomarkers, and their classification accuracy rates were 86.9% for recurrent EOC and non-recurrent EOC, and 88.7% for healthy?+?non-recurrent EOC and EOC?+?recurrent EOC. The results show that L-EDA is a powerful tool for potential biomarker discovery in metabonomics study.     

MiR-135a functions as a tumor suppressor in epithelial ovarian cancer and regulates HOXA10 expression

The activation of homeobox A10 (HOXA10) has been proved to be an important event in epithelial ovarian carcinogenesis, yet its regulation in epithelial ovarian cancer (EOC) is still not fully understood. Here, we aimed to reveal the mechanism that a predicted target miRNA regulates HOXA10 expression and the association of its expression with progression of EOC. Here, by using computer-assisted algorithms from PicTar, TargetScan, and miRBase, we identified that the predicted target miRNA of HOXA10 was miR-135a. MiR-135a expression in EOC tissues and controls was measured with quantitative RT-PCR. The role of miR-135a and HOXA10 in the growth and survival of several EOC cell lines was determined with several in vitro approaches. We found that miR-135a expression was downregulated in an EOC patient cohort. Also, patients with low miR-135a expression had shorter overall survival and progression-free survival durations than those with high expression. Functional analysis of three EOC-derived cell lines (SKOV-3, HEY, and OVCAR-3) demonstrated that miR-135a directly regulated HOXA10 expression by targeting its 3′-UTR. Inhibition of HOXA10 expression with miR-135a mimics and HOXA10 siRNA consistently resulted in cell apoptosis with concomitant enhancement of caspase-3, increase of p53 expression and reduction of Bcl-2 expression, and also suppressed cell growth and adhesion. These findings suggest that ubiquitous loss of miR-135a expression is a critical mechanism for the overexpression of HOXA10 in EOC cells, which is implicated in epithelial ovarian carcinogenesis. Furthermore, miR-135a may be predictive of EOC prognosis.     

上皮性卵巢癌组织miR-338-3p、miR-1294的表达及临床意义

摘要 目的：探讨上皮性卵巢癌组织中微小RNA（miR）-338-3p、miR-1294表达与患者临床病理参数的关系,并分析其表达对上皮性卵巢癌预后的影响。方法：收集2010年6月～2015年6月我院行手术治疗的上皮性卵巢癌患者的石蜡组织样本（癌组织和癌旁正常组织）,实时荧光定量PCR（RT-PCR）技术检测组织样本中miR-338-3p、miR-1294的表达情况;分析癌组织中miR-338-3p、miR-1294表达与患者临床病理参数的关系;Kaplan-Meier生存曲线分析miR-338-3p、miR-1294表达与患者预后的关系;Cox回归模型分析上皮性卵巢癌患者的预后影响因素。结果：与癌旁正常组织相比,上皮性卵巢癌组织中miR-338-3p、miR-1294表达均降低（均P<0.05）;miR-338-3p表达与组织学分级、淋巴结转移、FIGO分期相关（均P<0.05）;miR-1294表达与肿瘤直径、淋巴结转移、FIGO分期相关（均P<0.05）。Kaplan-Meier生存曲线结果显示,miR-338-3p低表达组患者、miR-1294低表达组患者的预后较差（均P<0.05）。Cox回归模型分析结果显示,淋巴结转移、较高FIGO分期、miR-338-3p低表达、miR-1294低表达是上皮性卵巢癌预后的危险因素（均P<0.05）。结论：上皮性卵巢癌组织中miR-338-3p、miR-1294均低表达,且均与较差临床病理参数、预后不良相关;miR-338-3p、miR-1294可能是上皮性卵巢癌患者预后预测的潜在指标。     

ROMA在卵巢上皮性癌早期诊断中的研究进展

卵巢上皮性癌（Epithelial ovarian cancer,EOC）死亡率居妇科恶性肿瘤首位,早期诊断可明显改善患者预后。人附睾上皮分泌蛋白（human epididymis protein 4,HE4）对早期EOC的检测敏感性高,有助于对EOC高危患者的筛选,与CA125可互补,增加盆腔包块患者中EOC早期诊断力度。HE4与CA125联合检测及结合绝经状态预测盆腔包块患者中卵巢恶性肿瘤的发病风险模型（Risk of Ovarian Malignancy Algorithm,ROMA）,能成功预测盆腔包块患者中EOC高风险个体,对卵巢良恶性肿瘤的鉴别预测更为准确且更易被接受,有较大的临床应用价值。     

The expression of a novel estrogen receptor, GPR30, in epithelial ovarian carcinoma and its correlation with MMP-9

The aim of the present study is to investigate the expression of a novel estrogen receptor, G protein-coupled receptor 30 (GPR30) and its correlation with matrix metalloproteinases-9 (MMP-9) in epithelial ovarian cancer (EOC). Ovary tissues were obtained from 39 female patients, including 30 cases of EOC and 9 cases of benign ovarian tumor. Four normal ovary tissues were used as control. Immunohistochemical staining was used to detect the expressions of GPR30 and MMP-9. Chi square test, Fisher's exact test and Spearman's rank correlation analysis were used for statistical analysis. The results showed that GPR30 overexpression rate in EOC cases was significantly higher than those in benign ovarian tumor and normal ovary cases. Whereas MMP-9 overexpression rate in EOC cases was significantly higher than that in normal ovary cases, without any difference to that in benign ovarian tumor cases. To demonstrate the relationship between GPR30 and clinicopathological variables of EOC, we further analyzed the pathology type, FIGO stage and age of patients sampled in our study. The analysis showed there were significant differences of GPR30 overexpression rate among various pathology types and different FIGO stages (P<0.05), and no significant difference of both GPR30 and MMP-9 among three age groups (P>0.05). Moreover, GPR30 expression was positively correlated with MMP-9 (r(s)=1.000, P=0.002). These results suggest that GPR30 may be involved in the invasion and metastasis of EOC, being a potential index of EOC early diagnosis and malignancy grade prediction.     

mRNA expression levels of the biological factors uPAR, uPAR-del4/5, and rab31, displaying prognostic value in breast cancer, are not clinically relevant in advanced ovarian cancer

High tumor tissue mRNA expression of the tumor biological factors uPAR, uPAR-del4/5, or rab31 is associated with shorter distant metastasis-free and overall survival in breast cancer patients. To evaluate whether these factors are also clinically relevant in ovarian cancer, we quantified the respective mRNA levels in primary tumor tissue of advanced ovarian cancer patients (n=103) and evaluated their association with clinicopathological parameters and patients' prognosis. mRNA expression levels of all three markers did not show any significant association with overall or progression-free survival, demonstrating that these factors have no prognostic value in advanced ovarian cancer.     

Role of DNA repair and cell cycle control genes in ovarian cancer susceptibility

Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different cancer diseases. For ovarian cancer, the known highly penetrant susceptibility genes (BRCA1 and BRCA2) are probably responsible for only 40 % of the excess familial ovarian cancer risks, suggesting that other susceptibility genes of lower penetrance exist. The aim of the present study was to evaluate the role of SNPs in three genes, XRCC2 (R188H), ERCC2 (K751Q) and CDKN1B (V109G) which are with moderate risk for ovarian cancer susceptibility in Egyptian women. We further investigated the potential combined effect of these genes variants on ovarian cancer risk. The three genes polymorphisms were characterized in 100 ovarian cancer Egyptian females and 100 healthy women by (RFLP–PCR) method in a case control study. Our results revealed that the frequencies of AC genotypes of ERCC2 (K751Q), and GG genotypes of CDKN1B (V109G) polymorphisms were significantly higher in EOC patients than in normal individual (P = 0.007, 0.02 respectively). The frequencies of AA genotype of XRCC2 (R188H) and CC genotype of ERCC2 (K751Q) were higher in EOC patients than in normal individual but without significance (P = 0.06, 0.38 respectively). Also, no association between any one of the three studied genes polymorphisms and the clinical characteristics of disease. The combination of GA (XRCC2) + AC (ERCC2) + GG (CDKN1B) was significantly associated with increased EOC risk. Also, the combination for GA (XRCC2) + AC (ERCC2) and the combination of AA (XRCC2) + CC (ERCC2) were significantly associated with increased EOC risk. There was significant difference in CA125 values between EOC and control Group (P < 0.001). Our results suggested that, XRCC2, ERCC2 and CDKN1B genes are important candidate genes for susceptibility to EOC. Also, gene–gene interaction between GA (XRCC2) + AC (ERCC2) + GG (CDKN1B) polymorphism may be associated with increased risk of EOCC in Egyptian women.     

MicroRNA-150 Predicts a Favorable Prognosis in Patients with Epithelial Ovarian Cancer,and Inhibits Cell Invasion and Metastasis by Suppressing Transcriptional Repressor ZEB1

MicroRNA (miR)-150 has been reported to be dramatically downregulated in human epithelial ovarian cancer (EOC) tissues and patients’ serum compared to normal controls. This study aimed to investigate clinical significance and molecular mechanisms of miR-150 in EOC. In the current study, quantitative real-time PCR analysis showed that miR-150 was significantly downregulated in human EOC tissues compared to normal tissue samples. Then, we demonstrated the significant associations of miR-150 downregulation with aggressive clinicopathological features of EOC patients, including high clinical stage and pathological grade, and shorter overall and progression-free survivals. More importantly, the multivariate analysis identified miR-150 expression as an independent prognostic biomarker in EOC. After that, luciferase reporter assays demonstrated that Zinc Finger E-Box Binding Homeobox 1 (ZEB1), a crucial regulator of epithelial-to-mesenchymal transition (EMT), was a direct target of miR-150 in EOC cells. Moreover, we found that the ectopic expression of miR-150 could efficiently inhibit cell proliferation, invasion and metastasis by suppressing the expression of ZEB1. Furthermore, we also observed a significantly negative correlation between miR-150 and ZEB1 mRNA expression in EOC tissues (rs = –0.45, P<0.001). In conclusion, these findings offer the convincing evidence that aberrant expression of miR-150 may play a role in tumor progression and prognosis in patients with EOC. Moreover, our data reveal that miR-150 may function as a tumor suppressor and modulate EOC cell proliferation, and invasion by directly and negatively regulating ZEB1, implying the re-expression of miR-150 might be a potential therapeutic strategy for EOC.     

β-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with typically extensive intraperitoneal implantation leading to poor prognosis. Our previous study preliminarily demonstrated β-hCG can promote tumorigenesis in immortalized nontumorigenic ovarian epithelial cells. In this study, the roles and mechanisms of β-hCG in regulating EOC proliferation and metastasis were thoroughly explored. First, histologically, β-hCG was aberrantly overexpressed in human EOC metastatic tissues, and significantly correlated with FIGO stage, tumor size, differentiation, histologic grade and high grade serous ovarian carcinoma (HGSOC) (P < 0.05). However, serologically, β-hCG expression showed no significant difference between EOC and nonmalignant ovarian patients. Second, β-hCG was confirmed to have no significant effects on EOC proliferation in vitro and in vivo, while β-hCG upregulation was proven to promote migration and invasion ability in ES-2 and OVCAR-3 cells in vitro (P < 0.05), and β-hCG downregulation in SKOV3 cells had the opposite effect. Moreover, more invadopodia protrusions, mitochondria accumulations and cytoskeletal rearrangements were observed in β-hCG-overexpressing ES-2 cells, while β-hCG-depleted SKOV3 cells produced the opposite effect. Furthermore, β-hCG was confirmed to clearly facilitate intraperitoneal metastasis in nude mouse orthotopic ovarian xenograft models. Importantly, these effects of β-hCG were mediated by activation of the ERK/MMP2 signaling pathway, independently of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) presence, and inhibition the pathway with the p-ERK1/2 inhibitor SCH772984 significantly impaired the tumor-promoting effects induced by β-hCG. Collectively, these data provide new insight into the roles and mechanisms of β-hCG in regulating EOC metastasis through ERK/MMP2 signaling pathway and may become a new target for therapeutic intervention.     

Eg5 high expression predicts dismal prognosis in epithelial ovarian cancer

The expression of kinesin spindle protein (Eg5) and its significance of clinical prognosis of patients with epithelial ovarian cancer (EOC) were evaluated in this study. Forty-five fresh frozen tissue samples for quantitative real-time polymerase chain reaction (qPCR) and 196 samples for immunohistochemistry (IHC) analysis with tissue microarray (TMA) were applied to characterize Eg5 mRNA and protein expressions in EOC. The correlation between clinical parameters and Eg5 protein expression was investigated using statistical analysis. The expression of Eg5 protein was significantly higher in EOC tissues compared with that in corresponding non-cancerous tissues (P < 0.05). The high Eg5 expression was significantly correlated with older age (P = 0.003), higher stage (P = 0.001), presence of metastasis (P = 0.041) and higher CA125 serum level (P = 0.013). For univariate analysis, associated prognostic markers in patients with ovarian cancer were analyzed for correlations with poor overall survival, including Eg5 (P = 0.011), age (P = 0.001), FIGO stage (P = 0.011), CA125 serum level (P = 0.001), lymph nodes (P = 0.012), and metastasis (P = 0.001). For multivariate analysis, Eg5 expression, FIGO stage and age were independent factors found contributing to a largely unfavorable prognosis in patients with ovarian cancer. In conclusion, the high expression of Eg5 is correlated with an unfavorable prognosis in EOC.     

卵巢癌组织ERCC1、Vimentin表达与临床病理特征及预后的关系分析

目的:探讨卵巢癌组织切除修复交叉互补基因(ERCC1)、波形蛋白(Vimentin)表达与临床病理特征及预后的关系。方法:选取2015年3月～2016年2月期间首都医科大学附属北京世纪坛医院收治的卵巢癌患者83例为研究对象,收集每位患者的卵巢癌组织样本、癌旁正常组织样本,采用免疫组化SP法对各组织标本中的ERCC1、Vimentin的阳性表达率、表达水平进行检测,并分析ERCC1、Vimentin表达与卵巢癌临床病理特征间的关系,并对患者进行统一的手术治疗,分析ERCC1、Vimentin阳性表达组与阴性表达组患者的预后。结果:卵巢癌组织的ERCC1、Vimentin的阳性表达率分别为54.22%(45/83)、69.88%(58/83),高于癌旁正常组织的9.64%(8/83)、20.48%(17/83),差异有统计学意义(P0.05)。卵巢癌组织的ERCC1、Vimentin的表达水平均高于癌旁正常组织(P0.05)。ERCC1、Vimentin的阳性表达率与卵巢癌患者的年龄、病灶直径、病理分型无关,而与卵巢癌肿瘤的临床分期、分化程度、淋巴结转移有关。ERCC1、Vimentin阳性表达组患者的无进展生存期(PFS)、总体生存期(OS)均短于ERCC1、Vimentin阴性表达组(P0.05)。结论:ERCC1、Vimentin的表达水平与卵巢癌的分期、分化程度、淋巴结转移有关,在卵巢癌的发生发展过程中起重要作用,ERCC1、Vimentin可能作为卵巢癌患者预后评估的参考指标。     

RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer

The RNA-binding motif protein 3 (RBM3) was initially discovered as a putative cancer biomarker based on its differential expression in various cancer forms in the Human Protein Atlas (HPA). We previously reported an association between high expression of RBM3 and prolonged survival in breast and epithelial ovarian cancer (EOC). Because the function of RBM3 has not been fully elucidated, the aim of this study was to use gene set enrichment analysis to identify the underlying biologic processes associated with RBM3 expression in a previously analyzed EOC cohort (cohort 1, n = 267). This revealed an association between RBM3 expression and several cellular processes involved in the maintenance of DNA integrity. RBM3-regulated genes were subsequently screened in the HPA to select for putative prognostic markers, and candidate proteins were analyzed in the ovarian cancer cell line A2780, whereby an up-regulation of Chk1, Chk2, and MCM3 was demonstrated in siRBM3-treated cells compared to controls. The prognostic value of these markers was assessed at the messenger RNA level in cohort 1 and the protein level in an independent EOC cohort (cohort 2, n = 154). High expression levels of Chk1, Chk2, and MCM3 were associated with a significantly shorter survival in both cohorts, and phosphorylated Chk2 was an adverse prognostic marker in cohort 2. These results uncover a putative role for RBM3 in DNA damage response, which might, in part, explain its cisplatin-sensitizing properties and good prognostic value in EOC. Furthermore, it is demonstrated that Chk1, Chk2, and MCM3 are poor prognostic markers in EOC.     

Effect of Ovarian Cancer Ascites on Cell Migration and Gene Expression in an Epithelial Ovarian Cancer In Vitro Model

A third of patients with epithelial ovarian cancer (EOC) present ascites. The cellular fraction of ascites often consists of EOC cells, lymphocytes, and mesothelial cells, whereas the acellular fraction contains cytokines and angiogenic factors. Clinically, the presence of ascites correlates with intraperitoneal and retroperitoneal tumor spread. We have used OV-90, a tumorigenic EOC cell line derived from the malignant ascites of a chemonaive ovarian cancer patient, as a model to assess the effect of ascites on migration potential using an in vitro wound-healing assay. A recent report of an invasion assay described the effect of ascites on the invasion potential of the OV-90 cell line. Ascites sampled from 31 ovarian cancer patients were tested and compared with either 5% fetal bovine serum or no serum for their nonstimulatory or stimulatory effect on the migration potential of the OV-90 cell line. A supervised analysis of data generated by the Affymetrix HG-U133A GeneChip identified differentially expressed genes from OV-90 cells exposed to ascites that had either a nonstimulatory or a stimulatory effect on migration. Ten genes (IRS2, CTSD, NRAS, MLXIP, HMGCR, LAMP1, ETS2, NID1, SMARCD1, and CD44) were upregulated in OV-90 cells exposed to ascites, allowing a nonstimulatory effect on cell migration. These findings were validated by quantitative polymerase chain reaction. In addition, the gene expression of IRS2 and MLXIP each correlated with prognosis when their expression was assessed in an independent set of primary cultures established from ovarian ascites. This study revealed novel candidates that may play a role in ovarian cancer cell migration.     

HMP19 is a new metastasis suppressor in epithelial ovarian cancer

HMP19 is a neuron-specific gene; its expression product belongs to a family of neuronal proteins which can be found in numerous kinds of human cancers. However, the clinicopathological significance of HMP19 expression in epithelial ovarian cancer (EOC) is as yet unknown. In this study, protein expression levels of HMP19 in cancerous tissues were determined by tissue microarray immunohistochemistry analysis (TMA-IHC) (n = 117). HMP19 protein levels in cancer tissues were associated with clinical characteristics and overall survival rates of patients with EOC. It was found that both mRNA and protein levels of HMP19 were significantly lower in EOC than those in normal ovary or fallopian tube tissues (P<0.05). The protein expression level of HMP19 was significantly associated with a lower FIGO stage, a lower level of CA-125 and a lower presence of metastasis. Consistent with related adverse clinical pathological features, the overall survival (OS) rate of patients with low or non HMP19-expressing tumors was inferior compared to those with high HMP19-expressing tumors. This is in accordance with further studies that found high HMP19 protein level to be an independent prognostic factor for OS in EOC. Multivariate analysis demonstrated that tumor patients with low HMP19 expression had an exceedingly poor OS. HMP19 plays a role in metastasis/tumor suppression and offers a prognostic value for EOC. HMP19, as a new inhibitor, strongly inhibits metastasis and partially attenuates tumor growth in EOC.     

Clinical significance of serum gastrin levels in patients with colorectal cancer

AIMS: An association between elevated serum gastrin levels and the presence of human colorectal cancer has been reported, and gastrin has been shown to stimulate the growth of experimentally induced colon neoplasia. The aim of this study was to determine the preoperative and postoperative concentrations of serum gastrin in 53 patients with colorectal cancer and to assess the correlation between gastrin levels and tumor characteristics and prognosis. MATERIALS AND METHODS: A prospective study was performed over a six-year period during which 53 patients received potentially curative surgery for colorectal cancer. The prognostic variables used for the analysis included age, sex, tumor site, stage and degree of differentiation, preoperative and postoperative serum values of carcinoembryonic antigen (CEA) and gastrin, cancer-related mortality, and survival. CEA and gastrin serum values were determined using radioimmunological methods. Follow-up was carried out with clinical and radiological tests. RESULTS: The mean preoperative gastrin concentration was 51.2+/-27.4 pg/mL (range 12-146). Significantly increased serum gastrin concentrations, which returned to normal after surgery, were detected only in patients with well-differentiated cancer (74.2+/-28.3 pg/mL; moderately differentiated, 52.1+/-23.8; poorly differentiated, 29.9+/-12.3, p=0.02). The prognosis was unrelated to serum gastrin level; instead, tumor stage, preoperative CEA value, and degree of differentiation affected patient survival. CONCLUSIONS: This study showed that the serum gastrin concentration is not an appropriate clinical oncogenic factor. Although occurring only in well-differentiated tumors, serum gastrin is unrelated to the prognosis of patients with colorectal cancer.