S100P在胃癌中的下调表达及意义

目的探讨S100P在胃癌组织中的表达情况及与胃癌临床病理参数间的关系。方法选取93例胃癌石蜡组织标本及相对应的部分冻存胃癌组织及其配对正常组织为研究对象,应用免疫组织化学、RT-PCR、Western Blot方法检测S100P在胃癌及癌旁组织中的表达。结果免疫组织化学分析表明,胃癌中S100P蛋白主要定位于胞质和胞核,在52.7% (49/93)的胃癌组织和几乎所有的正常胃黏膜中可检测到表达,与正常胃黏膜相比,胃癌组织中的表达明显下调,其下调表达与患者肿瘤的侵袭深度(P=0.006)及肿瘤的大小相关(P=0.001)。同时,S100P在核酸和蛋白水平的表达具有相关性（P=0.030）,不能够作为独立的预后因素（P=0.347）。结论S100P在胃癌组织中表达下调,其表达与肿瘤的侵袭转移及肿瘤大小相关,并可以作为判断患者预后的辅助指标。     

High expression of S100P is associated with unfavorable prognosis and tumor progression in patients with epithelial ovarian cancer

Accumulating evidence has demonstrated that S100P is involved in the tumorigenesis and progression of multiple cancers. In the current study, we evaluated the expression of S100P in epithelial ovarian cancer and assessed its relevance to clinicopathological characteristics. Moreover, we investigated the biological effects of S100P using A2780 and SKOV3 cells. S100P expression was significantly increased in epithelial ovarian cancer specimens compared with fallopian tube tissues and normal ovary tissues. And high expression of S100P in epithelial ovarian cancer samples was significantly associated with tumor stage (P<0.001), serum CA125 level (P=0.026), residual tumor (P<0.001), ascites (P<0.001) and lymph nodes metastasis (P<0.001). Multivariate Cox analysis showed that S100P expression was an independent prognostic factor of overall survival (OS) and progression free survival (PFS) (P=0.017 and 0.031, respectively). Functional assays showed that overexpression of S100P promoted cell proliferation and cell cycle progression but did not affect cell migration and invasion in A2780 and SKOV3 cells. These data suggest that S100P may contribute to tumor development in epithelial ovarian cancer and could be a useful marker for the prognosis of epithelial ovarian cancer patients.     

胰腺癌患者血清中S100A8与S100A9水平及其临床意义

目的检测胰腺癌患者血清S100A8与S100A9的水平及探讨其临床意义。方法收集胰腺癌患者90例,同期纳入体检健康者50例为对照组。检测两组研究者血清中S100A8和S100A9的水平。分析胰腺癌患者血清S100A8和S100A9水平与其临床病理特征的相关性。对所有患者疗后随访6个月,比较死亡组与存活组患者血清中S100A8和S100A9水平。结果胰腺癌患者血清中S100A8和S100A9水平显著高于对照组(P<0.01)。胰腺癌患者血清中S100A8和S100A9水平与患者年龄、性别、肿瘤部位无显著相关(P>0.05),与其分化程度、临床分期呈明显相关(P<0.01)。6个月随访结果:27例死亡,18例存活,其中死亡组患者入院时血清S100A8和S100A9水平明显高于存活组,比较有显著性差异(P<0.01)。结论胰腺癌患者血清中S100A8和S100A9水平明显提高,且与其恶性程度密切相关,可能对临床评估胰腺癌预后有一定参考价值。     

S100A2 is a predictive biomarker of adjuvant therapy benefit in pancreatic adenocarcinoma

BackgroundPrognosis of patients with pancreatic adenocarcinoma (PAC) remains poor. S100A2 has been recently suggested as a negative prognostic biomarker in PAC. We aimed to investigate its prognostic and/or predictive value in a large independent multicentric cohort of patients with resected PAC.MethodsSequential samples of 471 patients were retrospectively collected; 142 patients did not receive adjuvant treatment (30%) and 329 (70%) received an adjuvant treatment. We measured protein levels of S100A2 by semiquantitative immunohistochemistry with tissue microarrays and correlated with patients’ overall survival (OS) and disease-free survival (DFS).ResultsS100A2 protein status was obtained in 462 (98%) patients. Its expression was low, moderate or high in 59%, 12% and 2% of cases, respectively. It was not correlated with DFS or OS in the whole population, neither in the subgroup of patients who did not receive adjuvant treatment. However among patients who received an adjuvant therapy, moderate/high levels of S100A2 were significantly associated with longer OS and DFS in multivariate analysis (hazard ratios of 0.63, p = 0.022 and 0.67, p = 0.017, respectively), whereas low S100A2 was not. Interaction tests for adjuvant therapy were statistically significant both for the OS and the DFS (p = 0.001 and p = 0.023, respectively). On multivariate analysis, S100A2 retained independent predictive values (OS: p < 0.001, DFS: p = 0.003) with a significant benefit of adjuvant therapy for those patients with moderate/high S100A2.ConclusionsS100A2 expression predicts longer DFS and OS in patients treated with adjuvant therapy and should be evaluated as a predictive biomarker.     

EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer

Background:Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers.Methods:The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively recruited colorectal cancer patients, and associations with expression of S100A4, clinicopathological parameters and patient outcome were investigated.Results:One hundred and ninety-eight samples (72%) displayed positive membrane staining of the tumour cells, whereas 10 cases (4%) were borderline positive. EMMPRIN expression was associated with shorter metastasis-free, disease-specific and overall survival in both univariate and multivariate analyses. The prognostic impact was largely confined to TNM stage III, and EMMPRIN-negative stage III patients had an excellent prognosis. Furthermore, EMMPRIN was significantly associated with expression of S100A4, and the combined expression of these biomarkers conferred an even poorer prognosis. However, there was no evidence of direct regulation between the two proteins in the colorectal cancer cell lines HCT116 and SW620 in siRNA knockdown experiments.Conclusion:EMMPRIN is a promising prognostic biomarker in colorectal cancer, and our findings suggest that it could be used in the selection of stage III patients for adjuvant therapy.     

S100P sensitizes ovarian cancer cells to carboplatin and paclitaxel in vitro

Objective

To investigate the relationship between the S100P and the sensitivity of ovarian cancer to chemotherapeutics.

Method

We established stable cell lines of ovarian cancer cells, SKOV3 and OVCAR3, that overexpress human S100P. We also transiently transfected the parent cell lines with S100P-targeted siRNA for down-regulation of S100P expression. The sensitivity of all transfected and untransfected cell lines to carboplatin and paclitaxel was detected by MTT assay.

Results

For both cells, IC_50s decreased to carboplatin and paclitaxel (p < 0.05), with overexpression of S100P compared to untransfected cells. Alternatively, with down-regulation of S100P by siRNA, the IC₅₀ to carboplatin and paclitaxel increased in each case (p < 0.05), which was significantly higher compared to untransfected cells.

Conclusion

Changes in expression levels of S100P in SKOV3 and OVCAR3 cells results in variable susceptibility to carboplatin and paclitaxel. These data suggest that S100P contributes to chemosensitivity to carboplatin and paclitaxel in ovarian cancer cells.     

S100A14 is a novel independent prognostic biomarker in the triple‐negative breast cancer subtype

Triple‐negative breast cancer (TNBC) represents a heterogeneous subgroup with generally poor outcome and lack of an effective targeted therapy. Prognostic or predictive biomarkers to guide treatment decisions for this group of patients are needed. To evaluate the potential of S100A14 protein as a novel biomarker in TNBC, the protein expression of S100A14 was correlated with clinical outcomes in a Pilot Sample set and a Danish cohort of predominantly TNBC patients. Kaplan‐Meier analysis identified a prognostic impact of S100A14 on disease‐free survival and overall survival, showing that tumors with high S100A14 protein expression levels were significantly correlated with poor outcome in TNBC patients (p = 0.017; p = 0.038), particularly those in the basal‐like subgroup (p = 0.006; p = 0.037). Importantly, TNBC patients with high S100A14 expression, but tumor‐negative axillary lymph nodes (N?), had equally poor outcomes as those with tumor‐positive axillary lymph nodes (N+), while TNBC/N? patients with low S100A14 expression had a significantly better disease free survival (p = 0.013). Multivariate analysis revealed that S100A14 is an independent prognostic factor for TNBC patients (p = 0.024; p = 0.05). At the cellular level, S100A14 was found to be expressed in epithelial‐like, but not in mesenchymal‐like, TNBC cells in vitro. S100A14 is an independent prognostic factor in TNBC and a novel potential therapeutic target in TNBC.     

The role of S100A14 in epithelial ovarian tumors

S100A14 is an EF-hand calcium-binding protein that has been reported to be involved in the progression of many malignancies. However, its role in ovarian cancer has not yet been clarified. In this study, we investigated the significance of S100A14 expression in epithelial ovarian cancers (EOCs) as well as it''s mechanism of action. On both RNA and protein levels, S100A14 was overexpressed in transformed cells. Immunohistochemical staining demonstrated that S100A14 expression was associated with advanced stage (P < 0.001) and poor tumor grade (P < 0.001). Moreover, S100A14 overexpression was an independent prognostic factor for overall survival (HR = 4.53, P = 0.029). We also investigated S100A14''s functional role by employing lentiviral-mediated overexpression and knockdown in EOC cells. S100A14 overexpression promoted cell proliferation, tumorigenesis, migration, and invasion, whereas S100A14 knockdown inhibited these properties. TOV112D cells that overexpressed S100A14 also exhibited greater tumor growth potential in xenografted mice. S100A14 promoted such a malignant phenotype in EOC cells through the PI3K/Akt pathway. Taken together, our data indicate that S100A14 has a crucial role in EOC progression, and its overexpression is associated with poor prognosis. Further study of S100A14''s molecular mechanisms may lead to the development of a novel therapeutic target for ovarian cancer.     

S100P在低分化膀胱癌和前列腺癌鉴别诊断中的价值

目的:探讨S100P蛋白对低分化膀胱癌和前列腺癌的鉴别诊断价值.方法:采用免疫组织化学法检测S100P蛋白在正常膀胱黏膜、低分化膀胱癌、正常前列腺及低分化前列腺癌组织中的表达.结果:S100P蛋白在低分化膀胱癌组织、正常膀胱黏膜组织中的阳性表达率分别为86.67％ (26/30)和0％ (0/15),表达差异有统计学意义(P＜0.01);S100P蛋白在低分化前列腺癌组织、正常前列腺组织中的阳性表达率分别为6.67％ (2/30)和93.33％ (14/15),表达差异有统计学意义(P＜0.01).S100P在低分化膀胱癌和前列腺癌的阳性表达有显著差异(P＜0.01).结论:S100P对低分化膀胱癌和前列腺癌具有鉴别诊断价值.     

非小细胞肺癌患者血清中 S100 A4和 S100 A6表达及其临床意义

目的：探讨S100A4和S100A6在非小细胞肺癌患者血清中的表达及其临床意义。方法筛选非小细胞肺癌患者共36例,同期纳入健康体检者50例为对照组。采取酶联免疫吸附试验（ ELISA）法测定2组血清S100A4和S100A6水平;比较2组血清S100A4和S100A6水平,分析血清S100A4和S100A6水平与患者临床特征的相关性。2组随访2年,比较死亡患者与存活患者的血清S100A4和S100A6水平。结果与对照组比较,非小细胞肺癌组患者血清中S100A4和S100A6水平明显升高（P＜0．01）。血清S100A4和S100A6水平与非小细胞肺癌患者的年龄、性别及病理类型无相关性（P＞0．05）,而与肺癌患者的分化程度、TNM分期及淋巴结转移有显著性相关（P＜0．01）。随访2年共有10例患者死亡,26例存活;死亡患者入院时血清S100A4和S100A6水平明显高于存活组（P＜0．01）。结论非小细胞肺癌患者血清S100A4和S100A6水平明显升高,对非小细胞肺癌的诊断和预后判断具有一定临床价值。     

Characterization of apolipoprotein A-I as a potential biomarker for cholangiocarcinoma

Serum samples from 60 cholangiocarcinoma (CC), 60 benign diseases of hepatobiliary and 53 normal individuals were analysed by SELDI-TOF-MS (Surface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry). It was found that a 28 k m/z peak was significantly decreased in CC and retained discriminatory value between CC and normal group, also between CC and benign groups. Then 1-D, 2-D gel electrophoresis and tandem mass spectroscopy were employed to isolate and identify the protein that correlates with observed SELDI-TOF-MS (m/z) value. The results demonstrated that 28 k m/z peak was apolipoprotein A-I (ApoA-I) and its identity was further validated by immunodepletion and Western blotting analysis. Subsequently, it was inspiring found that the decreased level of ApoA-I analysed by enzyme linked immunosorbent assay was consistent with SELDI-TOF-MS analysis. Therefore, it suggested that ApoA-I could be a potential useful biomarker for CC.     

膀胱良、恶性上皮肿瘤中S100P的表达及临床意义

目的:探讨S100P在正常膀胱组织和膀胱良、恶性肿瘤中的表达和临床意义.方法:采用免疫组织化学SP法检测15例正常膀胱黏膜、20例内翻性乳头状瘤、72例膀胱癌(包括58例膀胱尿路上皮癌、9例膀胱腺癌和5例膀胱鳞状细胞癌)中S100P的表达.结果:膀胱癌中S100P的阳性表达率为86.11％ (62/72),显著高于正常膀胱移行上皮0％ (0/15)及内翻性乳头状瘤35％(7/20)两组(P＜0.05);S100P的阳性表达率随浸润深度、病理分级的增加及淋巴结的转移而升高(P＜0.05);S100P在膀胱尿路上皮癌中的阳性表达率较膀胱腺癌及鳞状细胞癌高,但差异无统计学意义(P＞0.05).结论:S100P在膀胱癌组织中高表达,与膀胱癌的浸润及转移密切相关,其可能在膀胱恶性上皮肿瘤的发生发展过程中发挥重要作用.     

Serum miR-26a as a diagnostic and prognostic biomarker in cholangiocarcinoma

In order to determine the diagnostic and prognostic value of miR-26a in Cholangiocarcinoma (CCA), we compared miR-26a levels in serum from 66 CCA patients and 66 healthy controls, which was followed by serum analysis between the pre-operative serum and post-operative serum of these CCA patients. We found the concentration levels of miR-26a in serum of CCA patients were significantly higher than that from healthy controls (P < 0.01). Furthermore, the concentration levels of miR-26a in the post-operative serum were significantly reduced when compared to the pre-operative serum (P < 0.001). High miR-26a in serum was correlated significantly with clinical stage, distant metastasis, differentiation status, and poor survival of CCA patients. More importantly, serum miR-26a was an independent prognostic marker for CCA. In conclusion, our results suggested that miR-26a in serum might be a potential and useful noninvasive biomarker for the early detection of CCA.     

siRNA沉默S100P基因对胰腺癌细胞的生长抑制作用

[目的]探讨小干扰RNA（siRNA）沉默S100P基因后对胰腺癌SW1990细胞株生长的影响。[方法]化学合成针对S100P基因的siRNA,用脂质体转染试剂将siRNA体外转染至人胰腺癌SW1990细胞中,48h后收集细胞,分别提取细胞总RNA和蛋白。用实时定量RT-PCR测定S100P基因mRNA水平的表达;免疫印迹测定S100P蛋白的表达;MTT法测定细胞的生长曲线。[结果]转染siRNA后,S100P基因在mRNA水平上表达减少了77%,蛋白表达降低了74%,均显著性低于对照组。siRNA-S100P明显抑制细胞生长。[结论]应用RNAi技术沉默S100P基因可以降低人胰腺癌SW1990细胞株中S100P表达,抑制细胞生长。     

S100A4蛋白在宫颈鳞癌中的表达及意义

目的　研究S10 0A4蛋白在宫颈鳞癌组织中的表达及其临床意义。方法　应用免疫组织化学SP法检测 65例宫颈鳞癌组织和10例正常宫颈组织中S10 0A4蛋白。结果　在正常宫颈组织中S10 0A4蛋白不表达 ;在宫颈鳞癌组织中S10 0A4蛋白的表达率为3 5 .4% ( 2 3 /65 ) ;与正常宫颈组织比较 ,差异具有显著性 (P <0 .0 1)。S10 0A4蛋白在宫颈鳞癌中的表达与临床分期和淋巴结转移有关 (P <0 .0 1) ,与组织学分级无关 (P >0 .0 5 ) ;阳性细胞在血管平滑肌细胞以及淋巴细胞中亦有表达。结论　S10 0A4蛋白和宫颈鳞癌的侵袭和转移密切相关 ;S10 0A4蛋白可作为判定宫颈鳞癌临床病理特征的重要指标     

钙结合蛋白S100A16在胰腺癌中的表达及临床意义

目的 探讨S100A16在胰腺癌中的表达及其临床意义。方法 免疫组织化学法检测S100A16蛋白在胰腺癌和胰腺癌旁组织的表达情况,分析S100A16阳性表达与患者临床病理参数和预后的关系。PPI预测与S100A16有直接相互作用的蛋白关系网络。结果 S100A16在癌组织中表达的阳性率明显高于癌旁组织（P=0.001）,血管浸润、淋巴结转移的患者S100A16表达更高。胰腺癌患者的总体生存时间与肿瘤大小、TNM分期和S100A16表达水平相关。多因素分析显示S100A16表达水平是胰腺癌患者预后的独立危险因素,S100A16高表达患者死亡风险增加1.5倍。PPI预测S100A16与S100A14、IL36G、PITX1、PERP在相互作用网络中具有重要作用。结论 S100A16高表达的胰腺癌患者预后差,S100A16阳性表达是胰腺癌的独立预后指标。     

Inflammation‐induced S100A8 activates Id3 and promotes colorectal tumorigenesis

The aberrant expression of S100A8 and S100A9 is linked to nonresolving inflammation and ultimately to carcinogenesis, whereas the underlying mechanism that allows inflammation to progress to specific cancer types remains unknown. Here, we report that S100A8 was induced by inflammation and then promoted colorectal tumorigenesis downstream by activating Id3 (inhibitor of differentiation 3). Using gene expression profiling and immunohistochemistry, we found that both S100A8 and S100A9 were upregulated in the chemically‐induced colitis‐associated cancer mouse model and in human colorectal cancer specimens. Furthermore, we showed that S100A8 and S100A9 acted as chemoattractant proteins by recruiting macrophages, promoting the proliferation and invasion of colon cancer cell, as well as spurring the cycle that culminates in the acceleration of cancer metastasis in a nude mouse model. S100A8 regulated colon cancer cell cycle and proliferation by inducing Id3 expression while inhibiting p21. Id3 expression was regulated by Smad5, which was directly phosphorylated by Akt1. Our study revealed a novel mechanism in which inflammation‐induced S100A8 promoted colorectal tumorigenesis by acting upstream to activate the Akt1‐Smad5‐Id3 axis.