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摘要:
目的 探讨HDAC6与P21WAF1在胃癌发生、发展中的作用及其相关性，为胃癌的早期诊断、治疗和判断预后提供依据。 方法 应用SP免疫组化法分别检测40例胃癌、30例癌前病变组及32例正常胃黏膜组中HDAC6及P21WAF1蛋白的阳性表达情况。 结果 HDAC6组织表达阳性率在胃癌，癌前病变及正常对照组依次降低，分别为65.0%，43.3%，15.6%（P < 0.01），P21WAF1组织表达阳性率在胃癌，癌前病变及正常对照组依次升高，分别为45.0%，63.3%和81.3%（P < 0.01）。HDAC6的表达在分化程度越低、分期越高和淋巴结转移胃癌组织中显著升高（P < 0.05）；P21WAF1蛋白阳性表达则相反，在分化程度越低、分期越高和淋巴结转移胃癌组织中显著降低（P < 0.05）。胃癌组织中HDAC6与P21WAF1的表达呈负相关（r=-0.495，P < 0.01）；癌前病变黏膜组织中HDAC6与P21WAF1的表达呈负相关（r=-0.451，P < 0.05）。 结论 HDAC6与P21WAF1的异常表达可能与促进胃癌的发生、发展和浸润转移有关。HDAC6可能通过下调P21WAF1的表达，导致并促进胃癌的发生发展。HDAC6和P21WAF1可能作为胃癌诊断和预后判断的指标及胃癌治疗的新靶点。 Abstract:Objective The current paper aims to investigate the HDAC6 and p21WAF1 expression, as well as their correlations, in gastric carcinoma and normal mucosa adjacent to carcinoma. The roles of these proteins in gastric carcinoma were also investigated. Methods Immunohistochemistry was performed to detect the HDAC6 and p21WAF1 expression in 40 specimens of gastric carcinoma, 30 specimens of precancerous lesions (chronic atrophic gastritis with intestinal metaplasia), and 32 specimens of normal mucosa adjacent to carcinoma. Results The expression of HDAC6 in gastric carcinoma, precancerous lesions, and normal mucosa was 65.0%, 43.3%, and 12.5%, respectively. Meanwhile, the positive rates of p21WAF1 in gastric carcinoma, precancerous lesions, and normal mucosa were 45.0%, 63.3%, and 81.3%, respectively. A significant difference among the expression of HDAC6 and p21WAF1 in the three groups (P< 0.01) was observed. In gastric carcinoma, the HDAC6 expression significantly increased in stage Ⅲ or Ⅳ tumors (P< 0.05), positive lymph-node metastasis, and poorly differentiated adenocarcinoma (P< 0.05). On the contrary, the p21WAF1 expression significantly decreased in stage Ⅲ or Ⅳ tumors (P< 0.05), positive lymph-node metastasis, and poorly differentiated adenocarcinoma (P< 0.05). A negative correlation was found between the HDAC6 and p21WAF1 expression in gastric carcinoma (r= -0.495; P< 0.01) and precancerous lesions (r= -0.451; P< 0.05). Conclusion HDAC6 may have an inhibitory effect on p21WAF1 and may promote the development, infiltration, and metastasis of gastric carcinoma. HDAC6 and p21WAF1 are possible molecular markers of gastric cancer and may be used in the diagnosis and prognosis and as therapeutic targets of gastric carcinoma. -
Key words:
- HDAC6 /
- p21WAF1 /
- Gastric carcinoma
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图 1 HDAC6在胃癌组织阳性表达，细胞质出现棕黄色颗粒（SP× 100）
Figure 1. Expression of HDAC6 in gastric carcinoma
图 2 HDAC6在胃癌前病变组织阳性表达，细胞质出现棕黄色颗粒（SP×100）
Figure 2. Expression of HDAC6 in precancerous lesions
图 3 P21WAF1在胃癌组织阳性表达，细胞核出现棕褐色颗粒（SP× 100）
Figure 3. Expression of p21WAF1in gastric carcinoma in the nuclei
图 4 P21WAF1在胃癌前病变组织阳性表达，细胞核出现棕褐色颗粒（SP×200）
Figure 4. Expression of p21WAF1in precancerous lesions in the nuclei
表 1 P21WAF1和HDAC6在胃癌组织、癌前病变及正常胃组织中的表达
Table 1. Expression of P21WAF1and HDAC6 in gastric carcinoma, precancerous lesions and normal mucosa
表 2 P21WAF1、HDAC6的表达与胃癌临床病理参数之间的关系
Table 2. Relationship of P21WAF1 and HDAC6 expression with clinicophathologic parameters of gastric carcinoma
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