Combined expression of S100A4 and Annexin A2 predicts disease progression and overall survival in patients with urothelial carcinoma

ObjectivesTo determine the expression patterns and prognostic value of S100A4 and Annexin A2 for urothelial carcinoma of the urinary bladder.Methods and materialsImmunohistochemical staining for S100A4 and Annexin A2 was performed in 315 archived radical cystectomies and 63 normal specimens. The immunoreactivity of these proteins was correlated to evaluate their clinical significance as prognostic factors.ResultsProtein levels of S100A4 and Annexin A2 were up-regulated in urothelial carcinoma compared with adjacent nontumor tissues. The increased expressions of S100A4 and Annexin A2 were associated with invasion depth, lymph node metastasis, and distant metastasis (P<0.05). High expression of S100A4 correlated with expression of Annexin A2. These alterations in expression were also associated with greater risk of disease progression and decreased chance of carcinoma-specific survival. Further multivariate analysis suggested that expressions of S100A4 and Annexin A2 were independent prognostic indicators for overall survival in urothelial carcinoma. The patients with S100A4-positive/Annexin A2-positive carcinomas presented the lowest 5-year survival rate compared with the other 3 groups.ConclusionsS100A4 and Annexin A2 proteins could be useful prognostic markers to predict tumor progression and prognosis in urothelial carcinoma. The expression patterns of S100A4/Annexin A2 interaction correlated well with the pathologic stage, disease progression, and carcinoma-specific survival. This finding could aid in identifying more biologically aggressive carcinomas and thus patients who might benefit from more intensive adjuvant therapy.     

S100A4和血管内皮生长因子C、D在胃癌组织中的表达及其与淋巴结转移和预后的关系

目的 观察人胃癌S100A4和血管内皮生长因子(VEGF)-C、VEGF-D的表达,探讨其与临床病理特征及预后的关系.方法 应用免疫组织化学方法检测108例人胃癌及20例癌旁组织中S100A4和VEGF-C、VEGF-D的表达.分析S100A4和VEGF-C、VEGF-D表达与患者年龄、性别、肿瘤大小、病理类型、浸润深度、淋巴结转移和肿瘤TNM分期的关系,并作预后分析.结果 S100A4和VEGF-C、VEGF-D在胃癌组织中的阳性率明显高于癌旁组织(P＜0.05).S100A4的表达与肿瘤大小和淋巴结转移有关(P＜0.05),VEGF-C的表达与淋巴结转移和TNM分期有关(P＜0.05),VEGF-D的表达与淋巴结转移和TNM分期无明显相关(P＞0.05),肿瘤组织内S100A4和VEGF-C两者表达呈正相关(P＜0.05).S100A4和VEGF-C、VEGF-D阳性胃癌患者5年生存率分别低于阴性患者,差异无统计学意义(P＞0.05).结论 S100A4和VEGF-C的表达与胃癌的淋巴结转移有关,S100A4可能参与VEGF-C淋巴管生成通路,在胃癌的淋巴结转移中发挥重要作用.     

S100A4和MMP-2在胃癌组织中的表达及与侵袭和转移的关系

目的:通过检测S100A4、基质金属蛋白酶2(matrix metalloproteinase 2,MMP-2)在胃癌组织中的表达,探讨其在胃癌转移中的作用.方法:应用免疫组织化学方法检测S100A4和MMP-2在正常胃黏膜(n=20)、胃癌组织(n=49)中的表达,比较二者在两种组织中的表达差异.结果:S100A4、MMP-2在胃癌组织中的阳性表达率分别为59.18%、67.35%,其染色强度随浸润深度、淋巴结转移和肿瘤分期的增加而增强(P<0.05);在胃癌的不同病理类型和分化程度亚组,S100A4和MMP-2的表达差异均无统计学意义(P>0.05);S100A4在正常胃黏膜组织不表达,MMP-2在正常胃黏膜组织中的表达率为20.00%.两者的表达率均显著低于胃癌组织中的表达率(P<0.01).S100A4和MMP-2在胃癌组织中的表达呈正相关(r=0.661,P<0.001).结论:S100A4、MMP-2在肿瘤侵袭转移中发挥了重要作用,联合检测S100A4和MMP-2的表达可用于评定胃癌的转移潜能.     

S100A8, S100A9, and the S100A8/A9 complex in circulating blood are not associated with prostate cancer risk-A re-evaluation study

BACKGROUND: To evaluate the diagnostic performance of plasma S100A8, S100A9, and the S100A8/A9 complex as novel markers to discriminate between benign and malignant prostatic diseases as recently suggested for S100A9. METHODS: The study included 90 prostate cancer (PCa) patients (pN0M0, n = 50; pN1M0, n = 27; M1, n = 13), 50 controls without PCa, and six patients within 72 hr after radical prostatectomy for repeated measurements. The S100 proteins were analyzed with specific ELISAs. Comparisons were made to the prostate-specific antigen (tPSA) and the ratio of free to tPSA (%fPSA). RESULTS: The plasma concentrations of the S100 proteins in controls had either significantly higher values (S100A8; P = 0.020) or the tendency to higher values compared with the results in PCa patients. Differences between the three PCa groups were almost negligible. No correlation could be found between S100 protein levels and PSA concentration (r(s) = -0.110 to 0.433, P = 0.317-0.433) or prostate volume (r(s) = -0.038 to 0.018, P = 0.676-0.844). Tumor stage and tumor grade had no observed effect on S100 protein concentrations. After prostatectomy, there were discordant elimination kinetics for PSA and the S100 proteins, as the S100 proteins partially increased while PSA continuously decreased. Analyses of receiver-operating curves showed that, compared with PSA, S100A8, S100A9, and S100A8/A9 did not improve the differentiation between patients with and without PCa, while the discrimination ability was significantly lower than that of %fPSA. CONCLUSIONS: Our re-evaluation study showed that S100A8, S100A9, and the complex S100A8/A9 were less indicative than %fPSA and that they are not suitable to replace PSA.     

BCSG1,S100A4,VEGF在乳腺肿瘤中的表达

目的 探讨BCSG1、S100A4和VEGF在人乳腺肿瘤中的表达情况,研究其在乳腺癌发生、发展中的生物学意义并观察其与乳腺癌浸润及转移的内在关系.方法 本研究通过对40例乳腺纤维腺瘤、62例乳腺浸润性导管癌组织(根据有无腋窝淋巴结转移分为1、2两组)及其癌旁组织48例,采用免疫组织化学技术SP法,对上述三指标的表达情况进行对比观察.结果 BCSG1、S100A4和VEGF在乳腺组织中的阳性表达四组比较差异均有统计学意义(P＜0.05).结论 乳腺癌组织中BCSG1、S100A4和VEGF阳性表达率升高,提示乳腺肿瘤的浸润和转移能力增强;三指标的阳性表达率和肿瘤病理分级呈正相关;联合检测三种指标的表达状况将有助于乳腺癌的早期诊断和预后判断.     

S100A4细胞核表达与胃癌淋巴结转移相关

目的探讨S100A4蛋白在胃癌组织中的细胞内定位及其表达情况及与胃癌临床病理参数的关系。方法分离10对新鲜胃癌组织及配对的正常胃黏膜的核蛋白及浆蛋白，用蛋白印迹法检测S100A4蛋白在细胞内的定位。用免疫组织化学方法检测131例胃癌患者的胃癌组织和20例转移性淋巴结中S100A4蛋白的表达。结果S100A4蛋白在胃癌组织细胞核的表达阳性率为24．4％（32／131）。细胞浆表达阳性率为38．2％（50／131）。在32例S100A4核表达阳性的胃癌病例中，30例（93．8％）有淋巴结转移。伴淋巴结转移的胃癌组织中，S100A4细胞核表达阳性率（29．1％）显著高于没有淋巴结转移的胃癌组织中的S100A4细胞核表达的阳性率（7．1％）（P=0．016）。结论在胃癌组织中发现细胞核表达S100A4，并与胃癌淋巴结转移有关。     

钙结合蛋白S100A2在肝癌中的表达及与肿瘤细胞增殖的关系

目的观察钙结合蛋白S100A2在原发性肝癌中的表达及与肿瘤细胞增殖的关系，探讨两者对肝癌患者预后的影响。方法采用免疫组织化学链霉菌抗生物素蛋白-过氧化酶（SP）法检测62例肝癌标本中S100A2的表达，同时用计算机图象分析技术对其DI值（DNA含量指数）进行检测。结果高／中分化组，无门脉／胆管浸润或淋巴结／远处转移的病例中，S100A2阳性表达率分别为77．27％、76．92％、80．00％；DI值分别为1．68±0．20、1．73±0．23、1．76±0．23；但随着肝癌分化程度的降低，出现门肘胆管浸润或发生淋巴结／远处转移，S100A2阳性表达率降低（50．00％、47．22％、50．00％）（Χ^2=4．39、5．53、5．07，P均〈0．05），而DI值明显升高（1．93±0．29、1．99±0．31、2．01±0．33）（t=3．612、3．794、3．379，P均〈0．01）。并且在短／中期生存患者中，S100A2阳性表达率（50．00％）明显低于长期生存者（100％）（Χ^2=10．05，P〈0．01），而DI值（1．88±0．25）却明显高于长期生存者（1．69±0．21）（t=2．606，P〈0．05）。S100A2的表达与DI值呈明显负相关（t=3．023，P〈0．05）。结论S100A2蛋白表达降低和高的DI值提示肝癌的低分化、高侵袭转移能力及预后不良，两者的联合检测对判断肝癌的恶性程度和预后具有重要的临床意义。     

Cav-1 mRNA、S100A4 mRNA 和 CD31 的表达与前列腺癌转移及生存率关系的研究

目的 研究前列腺癌组织中Cav-1 mRNA、S100A4 mRNA和CD31的表达,探讨其与前列腺癌转移及生存率的关系. 方法 选取2004年1月至2006年5月行前列腺癌根治术切除的癌组织标本42例和癌旁组织12例.患者年龄58 ～ 86岁,平均(71.6±7.6)岁.Gleason评分≤6分17例,7分12例,≥8分13例.TNM分期:T116例,T29例,T311例,T46例.骨转移8例,无骨转移34例.术前PSA＜4μg/L 4例,4～ 10 μg/L 10例,＞10 μg/L 28例.12例前列腺癌旁组织作为对照组,取自距离肿瘤1 ～2 cm或另一叶(镜下验证无癌细胞)的正常前列腺组织.采用原位杂交法检测42例前列腺癌切除标本和12例癌旁组织中Cav-1 mRNA、S100A4 mRNA的表达;用CD31标记血管内皮细胞,计数肿瘤组织的微血管密度( microvessel density,MVD);结合临床资料分析三者与前列腺癌Gleason评分、TNM分期、PSA值及有无骨转移等特性的关系. 结果 前列腺癌组织中Cav-1 mRNA 和S100A4 mRNA阳性表达率分别为35.7％ (15/42)和47.6％ (20/42),癌旁组织分别为0和8.3％(1/12),各组比较差异均有统计学意义(P＜0.05).Cav-1 mRNA和S100A4 mRNA阳性表达率均与前列腺癌Gleason评分、TNM分期及骨转移呈正相关.Cav-1 mRNA、S100A4 mRNA阴性表达者MVD分别为(62.8±10.4)/mm2和(63.3±12.0)/mm2,阳性表达者分别为(83.5±6.7)/mm2和(77.9±11.0 )/mm2,组间比较差异均有统计学意义(P＜0.05).Cav-1 mRNA表达阳性组和阴性组5年生存率分别为46.7％ (7/15)、85.2％ (23/27),组间比较差异有统计学意义(P＜0.05).S100A4 mRNA表达阳性组和阴性组5年生存率分别为50.0％ (10/20)、90.9％( 20/22),组间比较差异有统计学意义(P＜0.05). 结论 Cav-1 mRNA和S100A4 mRNA阳性表达、MVD增高可能与前列腺痛进展、骨转移有关.Cav-1、S100A4均可能促进前列腺癌微血管形成,导致癌细胞骨转移,降低患者生存质最和生存率.     

DLL4和S100A4在不同分子亚型乳腺癌组织中的表达及意义

目的 分析Delta样配体4(Delta-like ligand 4,DLL4)及S100钙结合蛋白A4 (S100 calcium binding protein A4,S100A4)在不同乳腺癌分子亚型组织中的表达并讨论其临床意义.方法 采用免疫组织化学SP法检测十堰市太和医院Luminal A型乳腺癌组织51例、Luminal B型乳腺癌组织26例、HER-2过表达型乳腺癌组织17例、基底细胞样型乳腺癌组织14例和乳腺癌癌旁组织40例中DLL4和S100A4的表达情况,并分析其与乳腺癌临床病理特征之间的关系.结果 在乳腺癌组织中,DLL4和S100A4的表达阳性率分别为67.6％ (73/108)和62.0％ (67/108),均高于其在癌旁组织中的表达阳性率[22.5％ (9/40),45.0％ (18/40)],P＜0.05.在不同乳腺癌分子亚型组织中,HER-2过表达型和基底细胞样型乳腺癌组织中DLL4和S100A4的表达阳性率均高于LuminalA型和LuminalB型(P＜0.05).有淋巴结转移的乳腺癌患者,DLL4和S100A4呈高表达(P＜0.05).乳腺癌组织中DLL4表达与S100A4表达呈正相关关系(rs=0.217,P＜0.01).结论 DLL4和S100A4在基底细胞样型和HER-2过表达型乳腺癌组织中呈高表达,与预后相关.DLL4和S100A4共同参与乳腺癌的发生、发展以及浸润转移过程.临床联合检测两种蛋白表达可评估乳腺癌的潜在转移和预后.     

S100A6对胃癌细胞侵袭转移的调控机制研究

目的探讨S100A6过表达对胃癌细胞侵袭转移的调控机制。方法收集1995年1月至2001年12月间经病理确诊的166例胃癌标本及其对应的癌旁组织、肝转移组织和淋巴结转移组织标本,采用免疫组织化学染色法检测标本中S100A6蛋白的表达情况及其与临床病理因素的关系：通过ChIP—Chip方法检测胃癌细胞株KAT03中S100A6可能调控的下游因子;将S100A6基因转染入胃癌细胞株AGS,通过细胞侵袭实验、RTQ—PCR方法分别检测转染组、阴性对照组和空白对照组中细胞的侵袭能力和侵袭转移相关因子CDK5和FLJ12438的mRNA表达。结果S100A6蛋白在癌旁组织细胞质中偶有低表达;而在胃癌、肝及淋巴结转移灶组织的肿瘤细胞质和（或）细胞核中均有高表达,且在侵袭边缘的肿瘤细胞的细胞核中表达较高,其高表达率为分别为67．5％（112／166）、92．9％（26／28）和100％（30／30）。S100A6表达与肿瘤浸润深度、淋巴结转移、脉管癌栓、远处转移及TNM分期有关（均P〈0．05）。S100A6可能作用于26个细胞侵袭转移有关基因的启动子部位。SIOOA6转染组的过膜细胞数为31．3±5．5,多于阴性对照组的7．7±1．5和空白对照组的9.3±2．1,差异有统计学意义（均P〈0．05）。CDK5mRNA在转染组中的表达水平显著高于阴性对照组和空白对照组（均P〈0．05）,而FLJ1243mRNA在转染组中的表达水平与另外两组的差异则无统计学意义（均P〉0．05）。结论S100A6可能通过调控下游侵袭相关因子如CDK5的表达,进而影响胃癌细胞的侵袭转移等恶性生物学行为。     

转移相关基因nm23和P53及S100A4在晚期胃癌中的表达及与侵袭转移的相关性研究

目的探讨转移相关蛋白（nm23和P53及S100A4）在晚期胃癌转移发展过程中的意义。方法应用组织芯片和免疫组织化学方法研究nm23、P53和S100A4在74例胃癌患者的癌、癌旁、淋巴结转移、远处转移（肝脏、胰腺、卵巢等）组织中的表达。结果同癌旁组织相比，癌组织中P53和S100A4表达明显升高（P〈0．01），而nm23的表达明显降低（P〈0．05）；同癌组织相比，淋巴结中nm23的表达明显降低（P〈0．05）。远处转移组织S100A4表达明显升高（P〈0．01）。3者的阳性表达与胃癌的部分恶性生物学行为有关。癌组织中nm23^＋／P53^＋、P53^＋／S100A4^＋和nm23^＋／S100A4^＋的基因表型比例分别为48例（64．9％）、50例（67．6％）和39例（52．7％），其中P53^＋／S100A4^＋、nm23^＋／S100A4^＋和nm23^＋／P53^＋／S100A4^＋均与胃癌的高转移潜能相关。结论nm23和S100A4在肿瘤转移中发挥了重要作用；联合检测nm23、P53和S100A4的表达可用于评定胃癌的转移潜能。     

siRNA抑制S100A4蛋白对人胃腺癌细胞增殖和凋亡及化疗敏感性的影响

目的 研究应用小干扰RNA沉默S100A4蛋白后对人胃腺癌细胞BGC-823增殖、凋亡及化疗敏感性的影响.方法 人胃腺癌BGC-823细胞系转染siRNA,RT-PCR检测转染效果后将对数期胃腺癌细胞分为干扰组、阴性对照组、正常对照组,MTT检测不同浓度奥沙利铂对胃腺癌细胞中效浓度IC50值;绘制细胞生长曲线;TUNEL法检测细胞凋亡;RT-PCR检测各组细胞mRNA变化;Western blot检测蛋白水平的变化,计量资料选用t检验,SPSS17.0分析RT-PCR检测各组细胞mRNA的变化,Western blot检测蛋白水平的变化,细胞生长曲线描述细胞增殖,TUNEL法检测细胞凋亡,MTT法检测不同浓度奥沙利铂对胃腺癌细胞中效浓度IC50值.计量资料以((x)±s)表示,多个样本比较采用单因素方差分析和LSD检验方法.P＜0.05为差异有统计学意义.结果 RT-PCR结果显示BGC-823细胞转染S100A4siRNA 48 h后,S100A4mRNA的表达量分别为:(0.674±0.011)、(0.652±0.021)、(0.345±0.040),正常对照组与干扰组相比差异有统计学意义(P =0.012,P＜0.05),阴性对照组与干扰组差异均有统计学意义(P =0.000,P＜0.05),正常对照组与阴性对照组差异无统计学意义(P =0.380,P＞0.05);Western blot结果显示BGC-823细胞转染S100A4 48 h后表达量明显下调分别为:(0.654±0.025)、(0.642 +0.014)、(0.317 +0.061),正常对照组与干扰组相比差异有统计学意义(P=0.01,P＜0.05),阴性对照组与干扰组差异均有统计学意义(P=0.000,P＜0.05),正常对照组与阴性对照组无统计学差异(P =0.341,P＞0.05).S100A4siRNA转染后人胃腺癌BGC-823细胞增殖下降;TUNEL法结果显示转染后凋亡明显增加;MTT结果表明人胃腺癌BGC-823单用奥沙利铂中效浓度IC50分别为56.31 μmol/L,转染后奥沙利铂中效浓度IC50为0.654 μmol/L.结论 本研究结果表明,siRNA沉默S100A4蛋白后抑制胃腺癌细胞增殖、诱导凋亡并提高奥沙利铂化疗敏感性,提示S100A4可能是治疗胃腺癌的有效靶点.     

A specific vascular endothelial growth factor receptor tyrosine kinase inhibitor enhances the antiproliferative effect of trastuzumab in human epidermal growth factor receptor 2 overexpressing breast cancer cell lines

Background

Trastuzumab has been found to have potent antiproliferative effects in human epidermal growth factor receptor 2 (HER-2)-overexpressing human breast tumors. Inhibition of vascular endothelial growth factor receptor (VEGFR), a protein often overexpressed in breast carcinoma, has been shown to induce apoptosis.

Methods

Breast carcinoma cell lines were cultured with increasing doses of trastuzumab and/or a VEGFR tyrosine kinase inhibitor (TKI). Growth inhibition and apoptosis were assessed after 5 days and 48 hours of treatment, respectively. Combination index values were calculated to determine the effectiveness of this drug combination.

Results

A dose-dependent growth inhibition was shown in all cell lines tested with the VEGFR TKI, whereas trastuzumab was effective only in the HER-2-positive cells. A synergistic interaction was shown in the HER-2-overexpressing cell lines, accompanied by an increase in apoptosis.

Conclusions

The combination of trastuzumab and a VEGFR TKI may be of therapeutic value in select breast cancer patients.     

S100A4蛋白在人非小细胞肺癌间质中的表达及其临床意义

目的 探讨S100A4蛋白在人非小细胞肺癌(NSCLC)间质中的表达及其临床意义,以确定其与肿瘤的侵袭、转移及预后的关系.方法 130例NSCLC 患者手术切除的肺癌组织标本,应用免疫组织化学方法(SP法)检测S100A4蛋白在肺癌组织间质中的表达,分析其与预后的关系.结果 S100A4蛋白在NSCLC间质表达的总阳性率为72.3%(94/130),在鳞状细胞癌、腺癌、腺鳞癌和大细胞癌间质表达的阳性率分别为84.3%、59.6%、70.0%和75.0%.S100A4蛋白在NSCLC间质的阳性表达与淋巴结转移(χ2=18.91,P=0.000)、远处转移(χ2=5.51,P=0.019)及TNM分期(χ2=21.54,P=0.000)明显相关.间质S100A4蛋白表达阳性患者3年生存率为36.2%(34/94),明显低于表达阴性的患者[63.9%(23/36),P=0.003].Cox风险比例模型分析结果表明,年龄≤50岁(OR=1.866)、有淋巴结转移(OR=1.826)、有远处转移(OR=6.224)、肿瘤低、未分化(OR=1.793)、TNM分期Ⅲ～Ⅳ期(OR=2.573)和间质中S100A4蛋白表达阳性(OR=1.776)是影响肺癌患者预后的危险因素.结论 S100A4蛋白在NSCLC间质中的表达与肺癌的侵袭、转移、分期及预后密切相关,它有希望成为一种能预测肿瘤进展及指导临床治疗的标记物.     

Prealbumin,platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in rheumatoid arthritis

Objectives

Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients.

Calcyclin (S100A6) Attenuates Inflammatory Response and Mediates Apoptosis of Chondrocytes in Osteoarthritis via the PI3K/AKT Pathway

ObjectiveTo clarify the regulatory effect of Calcyclin (S100A6) on chondrocytes apoptosis and its relationship with progression of osteoarthritis in an effort to explore potential therapeutic targets for osteoarthritis.MethodImmunofluorescence assay was produced to identify the rat chondrocyte sample and western blots assay was detected the expression changes of S100A6 between control group and osteoarthritis model which induced by interleukin‐1β. Adenovirus were transfected into the chondrocytes in vitro, in order to regulate the S100A6 expression. The influence of S100A6 on inflammatory reaction of osteoarthritis was detected by RT‐PCR. Also, Caspase‐3 activity assay and TUNEL assay were performed to evaluate the apoptosis changes. In addition, RT‐PCR and western blots were performed to verify that S100A6 mediated the PI3K/AKT signaling pathway. Through the usage of pathway regulator, we detected S100A6 produced the effect by mediating the PI3K/AKT pathway.ResultsWe determined the expression of S100A6 decreased in osteoarthritis model, the relative expression level in osteoarthritis model was about 0.5 fold compared with control group. Through adenovirus transfection we revealed that the inflammatory factors of osteoarthritis (interleukin‐6 and matrix metalloproteinase‐13) showed a negative correlation with the S100A6 expression. The relative expression level of interleukin‐6 and matrix metalloproteinase‐13 were 1.534 and 1.259 when S100A6 was up‐regulated and the values were up to 2.445 and 2.074, respectively, when S100A6 was down‐regulated. Also, the data verified the apoptosis could be reduced when the S100A6 was up‐regulated and be activated when the S100A6 was down‐regulated, the Caspase‐3 activity was 16.512 U/μg and 24.45 U/μg respectively. Similar results were shown in TUNEL assay, the apoptosis index was 4.46% and 31.44%, respectively. Additionally, the results of polymerase chain reaction and western blots both demonstrated that the expression level of PI3K and AKT were increased when S100A6 was up‐regulated, conversely the expression level of those two signal modules were reduced if the S100A6 was down‐regulated. More importantly, the apoptosis triggered by S100A6 can be offset by the PI3K/AKT pathway inhibitor and activator (LY294002 and IGF‐1), the values of Caspase‐3 activity and apoptosis index became close to the untreated osteoarthritis group. The experimental results in this study were statistically significant.ConclusionWe investigated that Calcyclin (S100A6) relieved the inflammation and mediated the chondrocyte apoptosis through PI3K/AKT pathway and we confirmed that S100A6 might be an attractive therapeutic target.