Prognostic role of CIP2A expression in serous ovarian cancer

Background:

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein expressed in several solid cancers. Our purpose was to study its role in serous ovarian cancer patients, and the association to clinicopathological variables and molecular markers.

Methods:

We collected retrospectively 562 consecutive serous ovarian cancer patients treated at the Helsinki University Central Hospital. We stained tumour tissue microarrays for CIP2A by immunohistochemistry and constructed survival curves according to the Kaplan–Meier method. Associations to clinicopathological and molecular markers were assessed by the χ²-test.

Results:

We found strong cytoplasmic CIP2A immunoreactivity in 212 (40.4%) specimens, weak positivity in 222 (42.4%) specimens, and negative in 90 (17.2%). Immunopositive CIP2A expression was associated with high grade (P<0.0001), advanced stage (P=0.0005), and aneuploidy (P=0.001, χ²-test). Cancerous inhibitor of protein phosphatase 2A overexpression was also associated with EGFR protein expression (P=0.006) and EGFR amplification (P=0.043). Strong cytoplasmic CIP2A immunopositivity predicted poor outcome in ovarian cancer patients (P<0.0001, log-rank test).

Conclusion:

Our results show that CIP2A associates with reduced survival and parameters associated with high grade in ovarian cancer patients, and may thus be one of the factors that identify aggressive subtype (type II) of this disease.     

High CIP2A immunoreactivity is an independent prognostic indicator in early-stage tongue cancer

Background:

No reliable prognostic markers exist for squamous cell carcinoma of the tongue, and its prognosis can even in early stages be unpredictable and survival poor despite treatment. A potential marker is oncoprotein cancerous inhibitor of PP2A (CIP2A), which acts as a prognostic marker in gastric and non-small cell lung cancers.

Methods:

We collected specimens of 73 stage T1N0M0 and T2N0M0 oral squamous cell carcinomas of the tongue, as well as samples from normal oral mucosa, dysplastic lesions, and invasive carcinomas (n=39). All samples were stained for CIP2A by immunohistochemistry. Survival curves were constructed according to the Kaplan–Meier method. The Cox proportional hazard model served for univariate and multivariate survival analysis.

Results:

High CIP2A immunoreactivity predicted poor survival in tongue cancer patients (P=0.027, logrank test). In multivariate survival analysis, CIP2A was an independent prognostic factor (HR 2.02, 95% confidence interval 1.07–3.82, P=0.030). Cytoplasmic CIP2A expression was higher in severe dysplasia than in mild dysplasia.

Conclusion:

Our results suggest that high CIP2A expression characterises aggressive disease. Acting as a prognostic marker it might be of help when choosing patients for adjuvant treatment in tongue cancer patients.     

GPNMB overexpression is associated with extensive bone metastasis and poor prognosis in renal cell carcinoma

Glycoprotein non-metastatic protein B (GPNMB) promotes bone metastasis (BM) in various types of cancer. However, GPNMB expression and its function in patients with renal cell carcinoma (RCC) and BM is still unknown. Therefore, the clinical significance of GPNMB and its biological function in RCC with BM was investigated in the present study. A total of 31 patients with RCC and BM were retrospectively collected. The association between GPNMB protein expression level on the primary tumor and the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier analysis was used to investigate the association between GPNMB expression and the prognosis of the patients. The effects of GPNMB inhibition on cell proliferation, migration and invasion in RCC cells were investigated using short hairpin (sh)RNA. High GPNMB expression level was significantly associated with the number (P=0.001) and the extent of BM (P=0.001), Fuhrman grade (P=0.037), and ERK expression level (P=0.003) of the primary tumor. In addition, GPNMB overexpression was significantly associated with poor prognosis with respect to overall survival time (P=0.001). Furthermore, a specific shRNA sequence targeting the GPNMB gene was constructed and transduced into the ACHN cell line, using a lentivirus vector to obtain a stable cell line with low mRNA expression level of GPNMB. Low GPNMB expression level inhibited RCC cell proliferation, which was measured using a Cell Counting Kit-8 assay. Cell migration and invasion ability was significantly decreased in GPNMB knockdown RCC cells compared with that in cells transduced with the negative control shRNA. In addition, the protein expression levels of phosphorylated ERK were lower in the GPNMB shRNA-transduced ACHN cells compared with those in the control cells. Therefore, these results suggested that GPNMB plays an important role in tumor progression in RCC with BM. Furthermore, it might serve as a predictive marker for BM and as a poor prognostic factor in RCC with BM. GPNMB downregulation suppressed the proliferation, migration and invasion of the RCC cells, which may be mediated through the inhibition of the ERK signaling pathway.     

干扰CIP2A表达对前列腺癌细胞增殖、凋亡和侵袭的影响

目的 探讨干扰蛋白磷酸酶2A癌性抑制因子(CIP2A)表达对前列腺癌细胞增殖、凋亡和侵袭的影响.方法 应用siRNA干扰前列腺癌DU-145细胞的CIP2A表达后,检测细胞的增殖及凋亡水平.采用实时定量PCR和蛋白质印迹法检测CIP2A的表达水平;采用MTT实验检测细胞增殖水平;采用流式细胞术检测细胞周期和凋亡水平;采用TranswellTM实验检测细胞侵袭水平.结果 siRNA干扰前列腺癌DU-145细胞的CIP2A表达,干扰效率为80%.培养120 h后,CIP2A siRNA组前列腺癌DU-145细胞的增殖率为(94.02±4.21)%,低于对照组的(135.21±4.13)%(P﹤0.05).CIP2A siRNA组G1期细胞所占比例为(58.07±2.10)%,高于对照组的(50.73±2.30)%(P﹤0.05).CIP2A siRNA组前列腺癌DU-145细胞的穿膜细胞数为(93.00±4.80)个,少于对照组的(143.00±15.80)个(P﹤0.05).结论 CIP2A在前列腺癌细胞的增殖、凋亡和侵袭中起着及其重要的作用,并有可能成为前列腺癌的治疗新靶点.     

Fascin在肾癌细胞系侵袭转移中的作用

目的:研究肌成束蛋白（Fascin）在肾癌细胞(ACHN,769-P)侵袭转移中的作用。方法:利用siRNA沉默Fascin基因在肾癌细胞中的表达,逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法（Western blot）检测Fascin基因的沉默效率。划痕实验和Transwell实验测定细胞的迁移侵袭能力变化。结果:RT-PCR及Western blot检测发现实验组Fascin基因的表达量明显低于空白对照组和阴性对照组,差异有统计学意义（P<0.05）。划痕实验和Transwell实验发现实验组细胞的迁移侵袭能力明显低于空白对照组和阴性对照组（P<0.05）。 结论:沉默肾癌细胞中的Fascin表达后,细胞的迁移侵袭能力明显减弱。     

CIP2A在子宫内膜样腺癌中的表达及临床意义

目的:探究蛋白磷酸酶2A(CIP2A)在子宫内膜样腺癌中的表达情况及临床意义。方法:选取2011年1月至2014年3月行手术切除并经病理证实的50例子宫内膜样腺癌(EAC)及同期行门诊刮宫术获取的40例正常增生期子宫内膜(NE)组织标本。应用RT-PCR、Western blot法检测EAC和NE组织中CIP2A mRNA及蛋白水平,免疫组化法检测CIP2A阳性表达情况。分析CIP2A在EAC和NE组织中的表达差异及与子宫内膜样腺癌临床病理特征的关系。采用Kaplan-Meier法分析CIP2A不同表达水平对患者预后生存的影响,通过COX分析预后独立危险因素。结果:免疫组化染色显示:CIP2A在子宫内膜样腺癌中呈高表达,阳性着色定位于细胞浆和细胞核中,EAC组织中CIP2A阳性表达率显著高于NE组织(P＜0.01)。RT-PCR和Western blot检测显示EAC组织中CIP2A mRNA及蛋白表达水平高于NE组织(P＜0.01)。CIP2A表达与EAC的组织学分级、FIGO分期、宫颈管受累情况、p53表达及Ki-67增殖指数有关（P＜0.05）。Kaplan-Meier法生存分析显示EAC患者5年无病生存率为92.0%、总生存率为88.0%;CIP2A表达、组织学分级、FIGO分期、肌层浸润深度、附件转移、脉管内癌栓及Ki-67增殖指数与患者预后不良相关（P＜0.05）。多因素分析显示,组织学分级、FIGO分期及脉管内癌栓是影响子宫内膜样腺癌患者预后生存的独立危险因素（P＜0.05）。结论:CIP2A在子宫内膜样腺癌中呈高表达,与患者总生存率下降相关,并非影响患者预后的独立危险因素。     

卵巢浆液性肿瘤组织CIP2A和p53表达临床意义探讨

目的探讨CIP2A和p53在卵巢浆液性腺癌（ovarian serous adenocarcinoma,OSA）和卵巢交界性浆液性肿瘤（ovarian borderline serous tumor,OBST）中表达及其与临床病理参数和预后相关性。方法选取南京军区南京总医院1998-04-29-2010-10-02原发性OSA手术切除标本95例;另外选取南京军区南京总医院2007-06-25-2010-11-09原发性OBST 11例和南京市妇幼保健院2005-08-17-2012-04-10原发性OBST 27例,总计38例OBST作为对照。应用免疫组织化学方法测定95例原发性OSA和38例OBST中CIP2A及p53的表达,运用χ2检验分析CIP2A和p53表达与临床病理参数关系,运用非参数Spearman相关系数检验两者之间的相关性,并对随访结果进行生存分析。结果 95例OSA中CIP2A和p53高表达率分别为76.8%和68.4%,38例OBST中CIP2A和p53的高表达率分别为13.2%和44.7%,CIP2A和p53在OSA中的表达均明显高于OBST,差异有统计学意义,P〈0.05。CIP2A的表达水平与区域淋巴结转移、临床分期、病理分级和复发有关,P〈0.05;p53的表达水平与患者年龄、区域淋巴结转移、病理分级和复发密切相关,P〈0.05。Spearman相关系数检验结果显示,CIP2A和p53在OSA中的表达呈正相关,r=0.271,P=0.008,两者协同表达。Kaplan-Meier和Cox回归多因素分析显示,OSA患者预后与CIP2A和p53的表达有关,CIP2A和p53高表达的患者预后差,P〈0.05,但两者均不是影响OSA预后的独立因素。结论 CIP2A和p53高表达提示OSA恶性程度高。联合应用CIP2A和p53免疫组化标志可作为临床评估OSA患者预后的生物学指标。     

CIP2A在膀胱尿路上皮癌组织中的表达及其临床意义

目的 研究蛋白磷酸酶2A癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A)在膀胱尿路上皮癌组织中的表达及其与临床病理特征的关系,探讨其成为膀胱尿路上皮癌预后指标的可行性.方法 应用RT-PCR和Western blot检测CIP2A mRNA和蛋白在25例膀胱尿路上皮癌和对应癌旁组织中的表达情况;应用组织芯片技术和免疫组织化学方法,检测CIP2A在117例膀胱尿路上皮癌和30例癌旁组织中的表达情况,分析CIP2A与膀胱尿路上皮癌患者临床病理特征及预后之间的关系.结果 CIP2A mRNA和蛋白在25例配对膀胱尿路上皮癌组织中的表达水平明显高于癌旁组织.免疫组织化学检测发现,膀胱尿路上皮癌组织中CIP2A蛋白的阳性表达率为76.9％(90/117),明显高于癌旁组织的6.7％ (2/30),差异有统计学意义(P＜0.001).CIP2A表达与肿瘤病理分级(P＜0.001)、临床分期(P＜0.001)、肿瘤大小(P=0.002)和淋巴结转移(P=0.046)有关,但与年龄、性别及肿瘤数目无关(P＞0.05).KaplanMeier单因素分析显示,CIP2A蛋白高表达是总体生存率和无复发生存率的影响因素(P＜0.001).Cox多因素风险比例模型显示,与总生存率相关的独立预后因素为临床分期、肿瘤病理分级和CIP2A表达,与无复发生存率相关的独立预后因素亦为临床分期、肿瘤病理分级和CIP2A表达.结论 CIP2A蛋白在膀胱尿路上皮癌组织中高表达,可能与膀胱尿路上皮癌的进展有关,其表达状态是膀胱尿路上皮癌患者独立预后因素.     

Expression of E-Cadherin and the PTEN Gene in Relation to Invasion and Metastasis of Gastric Carcinomas

Objective To observe the expression of PTEN and E-Cadherin in gastric carcinomas (GCs): and to investigate the relationship between their expression and the pathology and prognosis of patients with GC. Methods The proposed markers were detected inmmunohistochemicaily by using the SABC method in 100 post-operated specimens of GC. The results were statically analyzed by the chi-square and log rank tests. Results Both E-Cadherin and PTEN proteins were expressed in noncancerous rnucosa. They were reduced or lost in GCs. The abnormal rate of expression of E-Cadherin was 42.0%. The decreased rate of expression in the diffuse-type GC (48.6%) was significantly higher than in the intestinaltype GC (26.7%, P< 0.05). The abnormal expression of E-Cadherin closely correlated to the depth of invasion (P< 0.05). The degree of loss of the PTEN protein was 59.0% in GCs. In the diffuse-type GC, the rate of toss of PTEN was (65.7%) which was significantly higher than that in the intestinal-type GC (43.3%,P< 0.05). The rate of loss of PTEN (64.5%) in GCs with lymph node metastasis was significantly higher than that in GCs without metastasis (41.7%, P< 0.05). The prognosis of patients with a loss of PTEN protein was worse than the patients with positive expression of PTEN (P=0.0066). E-Cadherin was normally expressed in 65.9% of GCs with positive expression of PTEN. Conclusion The loss of E-Cadherin and PTEN markers correlated with infusion and metastasis of GC. The expression of PTEN showed a close relationship to the prognosis of patients. Detection of the 2 markers together aided in the correct prediction of the prognosis of the GC patients and provided information for clinical treatment.     

Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially haematogenous metastasis, of colorectal cancer

Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs), known to inhibit cyclooxygenase (COX), reduce the risk of colorectal cancer. COX is a key enzyme in prostaglandin biosynthesis, and two isoforms of COX, COX-1 and COX-2, have been identified. Recently COX-2 has been reported to frequently overexpress in colorectal neoplasms and to play a role in colorectal tumorigenesis and tumour progression. In this study, using immunohistochemistry, we examined COX-2 expression in advanced human colorectal cancer and its correlation with clinicopathological features. COX-2 expression was observed mainly in the cytoplasm of cancer cells in all the specimens examined, but some stromal cells and endothelial cells were also stained. According to the grade of COX-2 expression of the cancer cells, patients were divided into high- and low-COX-2 expression groups. High-COX-2 expression significantly correlated with tumour recurrence, especially haematogenous metastasis. These results suggest that a selective COX-2 inhibitor can be a novel class of therapeutic agents not only for tumorigenesis but also for haematogenous metastasis of colorectal cancer. To our knowledge, this is the first report on the correlation between COX-2 overexpression and recurrence of colorectal cancer.     

Annexin A2与肿瘤侵袭和转移关系的研究进展

肿瘤的发生、发展是一个多步骤的复杂过程,涉及细胞内多分子异常、肿瘤细胞及肿瘤微环境的相互作用等多方面因素.尽管外科手术、放射治疗和化学治疗已取得了巨大的进步,但是在阻断肿瘤进程上并未有实质性突破.肿瘤的侵袭和转移是决定肿瘤患者死亡的关键因素.目前研究表明,Annexin A2广泛参与肿瘤细胞的黏附、增殖、侵袭、转移和新生血管的生成.因此临床上研究Annexin A2与肿瘤侵袭和转移的关系能为肿瘤的治疗提供依据和参考.本文就Annexin A2的特性、Annexin A2在肿瘤细胞中的表达,尤其对Annexin A2与各类型肿瘤侵袭和转移的关系展开综述.     

CIP4 promotes metastasis in triple-negative breast cancer and is associated with poor patient prognosis

Signaling via epidermal growth factor receptor (EGFR) and Src kinase pathways promote triple-negative breast cancer (TNBC) cell invasion and tumor metastasis. Here, we address the role of Cdc42-interacting protein-4 (CIP4) in TNBC metastasis in vivo, and profile CIP4 expression in human breast cancer patients. In human TNBC cells, CIP4 knock-down (KD) led to less sustained activation of Erk kinase and impaired cell motility compared to control cells. This correlated with significant defects in 3D invasion of surrounding extracellular matrix by CIP4 KD TNBC cells when grown as spheroid colonies. In mammary orthotopic xenograft assays using both human TNBC cells (MDA-MB-231, HCC 1806) and rat MTLn3 cells, CIP4 silencing had no overt effect on tumor growth, but significantly reduced the incidence of lung metastases in each tumor model. In human invasive breast cancers, high CIP4 levels was significantly associated with high tumor stage, TNBC and HER2 subtypes, and risk of progression to metastatic disease. Together, these results implicate CIP4 in promoting metastasis in TNBCs.     

Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma

RASSF2 can bind directly to K-Ras and function as a negative effector of Ras protein. RASSF2A is the only isoform of RASSF2 that contains CpG islands in its promoter and it has been reported to be inactivated by its promoter methylation in several human cancers. In the present study, we investigated the correlation of RASSF2A expression with its promoter methylation in nasopharyngeal carcinoma (NPC). Expression of RASSF2A was down-regulated in 80% (4/5) of NPC cell lines. Decreased RASSF2A expression was also observed in NPC primary tumors compared with normal nasopharyngeal epithelia. Promoter methylation of RASSF2A could be detected in all the RASSF2A-silenced cell lines (4/5) of the NPC cell lines and 50.9% (27/53) of primary tumors, but not in any of the normal epithelia. RASSF2A-methylated cases showed a significantly lower level of RASSF2A expression than unmethylated cases. Loss of RASSF2A expression can be greatly restored by the methyltransferase inhibitor 5-aza-dC in NPC cell lines. In addition, patients with methylated RASSF2A presented a higher frequency of lymph node metastasis (p < 0.05). Ectopic expression of RASSF2A in RASSF2A-silenced and -methylated NPC cell line CNE2 shows that RASSF2A could inhibit cell cycle progression, colony formation and cell migration, which provided further evidence that RASSF2A is a candidate tumor suppressor gene. In conclusion, RASSF2A, a candidate tumor suppressor gene (TSG), is frequently inactivated by its promoter methylation and this aberrant methylation correlates with lymph node metastasis in NPC.     

MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis

MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of noncoding RNAs. Here, we focused on the function and molecular mechanism of miR-1 and its potential clinical application in clear cell renal cell carcinoma (ccRCC). First, miR-1 was significantly downregulated in 87.8% renal cancer samples compared with corresponding noncancerous tissues (NCT), which was significantly associated with clinical stage, T classification and poor overall survival. Functional study demonstrated that enforced overexpression of miR-1 in renal cancer cells inhibited proliferation and metastasis in vitro and in vivo. Conversely, miR-1 inhibitor silencing miR-1 expression promoted cell proliferation and metastasis in ccRCC. CDK4, CDK6, Caprin1 and Slug were each directly targeted for inhibition by miR-1 and restoring their expression reversed miR-1-mediated inhibition of cell cycle progression and metastasis. Taken together, our findings established a tumor suppressive role for miR-1 in the progression of ccRCC by targeting CDK4, CDK6, Caprin1 and Slug and suggested miR-1 can be served as a novel potential therapeutic target for ccRCC.     

Improving the accuracy of pre-operative survival prediction in renal cell carcinoma with C-reactive protein

Background:

Validated objective biomarkers are needed for patients with renal cell carcinoma (RCC) to guide patient management and define high-risk populations for follow-up or for therapeutic purposes.

Methods:

Patients undergoing nephrectomy for RCC (n=286 all stages, 84% with conventional clear cell type) were included with a median duration follow-up of 5 years. The prognostic significance of pre-operative haematological and biochemical variables, including C-reactive protein (CRP) values were examined and whether they added additional information to a recently published pre-operative scoring system was determined.

Results:

C-reactive protein was the most significant predictor of overall survival (OS; χ²=50.9, P<0.001). Five-year OS for patients with CRP⩽15 mg l⁻¹ vs >15 mg l⁻¹ was 72% (95% CI 65–78%) and 33% (95% CI 23–44%), respectively. Similar results were seen for cancer-specific survival (CSS) and disease-free survival. On multivariate analysis, CRP remained highly significant for CSS (χ²=17.3, P<0.0001) and OS (χ²=9.8, P<0.002), in addition to other pre-operative variables including log of neutrophil/lymphocyte ratio, red blood cell count and white cell count. C-reactive protein was significant in addition to the pre-operative nomogram score (χ²=12.5, P=0.0004 for OS, χ²=16.2, P=0.0001 for CSS and χ²=8.6, P=0.003 for DFS) and was still significant when other pre-operative variables were included.

Conclusion:

C-reactive protein and other haematological and biochemical variables have independent prognostic significance in RCC and may enhance pre-operative scoring systems.     

CIP2A is a candidate therapeutic target in clinically challenging prostate cancer cell populations

Residual androgen receptor (AR)-signaling and presence of cancer stem-like cells (SCs) are the two emerging paradigms for clinically challenging castration-resistant prostate cancer (CRPC). Therefore, identification of AR-target proteins that are also overexpressed in the cancer SC population would be an attractive therapeutic approach.Our analysis of over three hundred clinical samples and patient-derived prostate epithelial cultures (PPECs), revealed Cancerous inhibitor of protein phosphatase 2A (CIP2A) as one such target. CIP2A is significantly overexpressed in both hormone-naïve prostate cancer (HN-PC) and CRPC patients. CIP2A is also overexpressed, by 3- and 30-fold, in HN-PC and CRPC SCs respectively. In vivo binding of the AR to the intronic region of CIP2A and its functionality in the AR-moderate and AR-high expressing LNCaP cell-model systems is also demonstrated. Further, we show that AR positively regulates CIP2A expression, both at the mRNA and protein level. Finally, CIP2A depletion reduced cell viability and colony forming efficiency of AR-independent PPECs as well as AR-responsive LNCaP cells, in which anchorage-independent growth is also impaired.These findings identify CIP2A as a common denominator for AR-signaling and cancer SC functionality, highlighting its potential therapeutic significance in the most clinically challenging prostate pathology: castration-resistant prostate cancer.     

Oncogenic nexus of cancerous inhibitor of protein phosphatase 2A (CIP2A): An oncoprotein with many hands

Oncoprotein CIP2A a Cancerous Inhibitor of PP2A forms an “oncogenic nexus” by virtue of its control on PP2A and MYC stabilization in cancer cells. The expression and prognostic function of CIP2A in different solid tumors including colorectal carcinoma, head & neck cancers, gastric cancers, lung carcinoma, cholangiocarcinoma, esophageal cancers, pancreatic carcinoma, brain cancers, breast carcinoma, bladder cancers, ovarian carcinoma, renal cell carcinomas, tongue cancers, cervical carcinoma, prostate cancers, and oral carcinoma as well as a number of hematological malignancies are just beginning to emerge. Herein, we reviewed the recent progress in our understanding of (1) how an “oncogenic nexus” of CIP2A participates in the tumorigenic transformation of cells and (2) how we can prospect/view the clinical relevance of CIP2A in the context of cancer therapy. The review will try to understand the role of CIP2A (a) as a biomarker in cancers and evaluate the prognostic value of CIP2A in different cancers (b) as a therapeutic target in cancers and (c) in drug response and developing chemo-resistance in cancers.     

CIP2A、IGF-2、PCNA、NGF及c-Myc在老年胶质瘤中的表达及其与预后的关系

目的 探讨CIP2A、IGF-2、PCNA、NGF及c-Myc在老年胶质瘤中的表达及其与预后的关系.方法检测CIP2A、IGF-2、PCNA、NGF及c-Myc在老年胶质瘤中的表达情况,对其进行多因素分析,探讨与老年胶质瘤的关系.结果CIP2A在Ⅰ～Ⅱ级老年胶质瘤组织中阳性表达率为50.00％,在Ⅲ～Ⅳ级中阳性表达率为77.78％,而对照组为12.50％;c-Myc在Ⅰ～Ⅱ级胶质瘤组织中阳性表达率为45.45％,在Ⅲ～Ⅳ级中阳性表达率为72.22％,而对照组为17.50％;NGF在Ⅰ～Ⅱ级老年胶质瘤中阳性表达率为40.91％,在Ⅲ～Ⅳ级中阳性表达率为83.33％,而在对照组中无表达;IGF-2在Ⅰ～Ⅱ级和Ⅲ～Ⅳ级胶质瘤组织中阳性表达率均为100.00％,而在对照组中无表达;PC-NA主要表达于胶质瘤细胞的细胞核之中,在Ⅰ～Ⅱ级胶质瘤组织中阳性表达率为45.45％,在Ⅲ～Ⅳ级为83.33％,而在对照组中无表达.观察组CIP2A、IGF-2、PCNA、NGF及c-Myc阳性表达率均高于对照组(P﹤0.05).在观察组中,Ⅲ～Ⅳ级胶质瘤中CIP2A、PCNA、NGF及c-Myc阳性表达率均高于Ⅰ～Ⅱ级胶质瘤阳性表达率(P﹤0.05).Logistic多元回归分析结果显示,CIP2A、IGF-2、PCNA、NGF与c-Myc是影响老年胶质瘤表达的独立因素.结论CIP2A、IGF-2、PCNA、NGF及c-Myc在老年胶质瘤中的表达与胶质瘤恶性程度有关,均可作为诊断老年胶质瘤的重要指标,为预测预后、判断胶质瘤生物学行为提供依据.     

潜在的癌症治疗靶点:癌蛋白CIP2A

蛋白磷酸酶在细胞的生命活动中起着关键作用,其中蛋白磷酸酶2A(protein phosphatase 2A,PP2A)可抑制多个关键致癌信号通路的活性,是一种重要的肿瘤抑制因子。因此,抑制PP2A的活性是人体正常细胞转化为癌细胞的条件之一。PP2A的癌性抑制剂(cancerous inhibitor of protein phosphatase 2A,CIP2A)是恶性肿瘤细胞中PP2A的内源性抑制剂,它的异常表达可导致PP2A失活。多项研究已证实了CIP2A在促进肿瘤生长、抗凋亡和肿瘤衰老诱导疗法中的作用。值得注意的是,高水平的CIP2A预示着多种癌症患者的预后不良。癌蛋白MYC(PP2A去磷酸化调节的癌蛋白之一)第62位丝氨酸的磷酸化水平可指示CIP2A的致癌活性。CIP2A和MYC之间的正反馈通路提高了MYC在癌细胞中的活性。此外,CIP2A还可提高其他癌蛋白的磷酸化水平及其活性,包括E2F1、AKT和mTORC1。然而,CIP2A对于正常小鼠的生长发育并不是必不可少的。这些研究结果表明,在癌细胞中靶向CIP2A进而重新激活PP2A不失是一种癌症靶向治疗的新策略。本文将对靶向CIP2A的肿瘤治疗方法及其可行性进行讨论。