肿瘤组织中热休克蛋白（HSPA12A、HSP90B1、HSPA4、HSPA5 和 HSPA6）的上调与 HBV 相关早期肝细胞癌的不良预后相关。
Upregulation of heat shock proteins (HSPA12A, HSP90B1, HSPA4, HSPA5 and HSPA6) in tumour tissues is associated with poor outcomes from HBV-related early-stage hepatocellular carcinoma.
机构信息
1. Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;
2. Department of Integrative Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; ; 3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
出版信息
Int J Med Sci. 2015 Feb 15;12(3):256-63. doi: 10.7150/ijms.10735. eCollection 2015.
BACKGROUND
Heat shock proteins (HSPs) are overexpressed in human hepatocellular carcinoma (HCC) tissue and correlate with aggressiveness and prognosis of HCC.
METHODS
Using the GSE14520 microarray expression profile from Gene Expression Omnibus, we compared HSP gene expression between tumour and non-tumour tissues and correlated this with outcomes in HCC patients.
RESULTS
We analysed 220 hepatitis B virus (HBV)-related HCC patients and 25 HSPs in this study. With the exception of HSPA4L, HSPA12A and HSPB8, members of the HSP family, including HSPH1, HSPBP1, HSPA1A, HSPA1B, HSPA1L, HSPA2, HSPA4, HSPA5, HSPA8, HSPA9, HSPAA1, HSPAB1, HSPA14, HSPB11, HSPA13, HSP90B1 and HSPBAP1, were all overexpressed in tumour tissues (all P < 0.001). In contrast, HSPB6, HSPB7, HSPA6, HSPB2 and HSPB3 were upregulated in non-tumour tissues (all P < 0.001). Multivariate analysis showed that cirrhosis (HR = 5.282, 95% CI = 1.294-21.555, P = 0.02), Barcelona Clinic liver cancer (BCLC) staging (HR = 2.151, 95% CI = 1.682-2.750, P < 0.001), HSPA12A (HR = 1.042, 95% CI = 1.003-1.082, P = 0.033) and HSP90B1 (HR = 1.001, 95% CI = 1.000-1.001, P = 0.011) were negatively associated with survival of HBV-related HCC patients. Furthermore, advanced BCLC staging (HR = 1.797, 95% CI = 1.439-2.244, P < 0.001) was also associated with earlier recurrence of HCC. The high expression of HSPA4 (HR = 1.002, 95% CI = 1.000-1.004, P = 0.019), HSPA5 (HR = 1.0, 95% CI = 1.0-1.0, P = 0.046) and HSPA6 (HR = 1.008, 95% CI = 1.001-1.015, P = 0.021) was similarly associated with HCC recurrence.
CONCLUSIONS
The expression of most HSPs was higher in tumour tissues than in non-tumour tissues. High BCLC staging scores, advanced cirrhosis and the overexpression of HSPA12A and HSP90B1 might be associated with poor survival from HCC, whereas high levels of HSPA4, HSPA5 and HSPA6 might be associated with earlier recurrence of HCC.
背景
热休克蛋白（HSPs）在人肝细胞癌（HCC）组织中过度表达，与 HCC 的侵袭性和预后相关。
方法
使用来自基因表达综合数据库（GSE14520）的微阵列表达谱，我们比较了肿瘤组织和非肿瘤组织中 HSP 基因的表达，并将其与 HCC 患者的结局相关联。
结果
我们分析了 220 例乙型肝炎病毒（HBV）相关 HCC 患者和 25 种 HSPs。除了 HSPA4L、HSPA12A 和 HSPB8 外，HSP 家族的成员，包括 HSPH1、HSPBP1、HSPA1A、HSPA1B、HSPA1L、HSPA2、HSPA4、HSPA5、HSPA8、HSPA9、HSPAA1、HSPAB1、HSPA14、HSPB11、HSPA13、HSP90B1 和 HSPBAP1，在肿瘤组织中均过度表达（均 P<0.001）。相比之下，HSPB6、HSPB7、HSPA6、HSPB2 和 HSPB3 在非肿瘤组织中上调（均 P<0.001）。多变量分析显示，肝硬化（HR=5.282，95%CI=1.294-21.555，P=0.02）、巴塞罗那临床肝癌（BCLC）分期（HR=2.151，95%CI=1.682-2.750，P<0.001）、HSPA12A（HR=1.042，95%CI=1.003-1.082，P=0.033）和 HSP90B1（HR=1.001，95%CI=1.000-1.001，P=0.011）与 HBV 相关 HCC 患者的生存时间呈负相关。此外，BCLC 分期较晚（HR=1.797，95%CI=1.439-2.244，P<0.001）也与 HCC 复发较早相关。HSPA4（HR=1.002，95%CI=1.000-1.004，P=0.019）、HSPA5（HR=1.0，95%CI=1.0-1.0，P=0.046）和 HSPA6（HR=1.008，95%CI=1.001-1.015，P=0.021）的高表达也与 HCC 复发相关。
结论
大多数 HSPs 在肿瘤组织中的表达高于非肿瘤组织。较高的 BCLC 分期评分、晚期肝硬化以及 HSPA12A 和 HSP90B1 的过度表达可能与 HCC 患者的生存不良相关，而 HSP4、HSPA5 和 HSPA6 的高水平可能与 HCC 的早期复发相关。
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