RAD50/MRE11/NBS1 proteins in relation to tumour development and prognosis in patients with microsatellite stable colorectal cancer
RAD50/MRE11/NBS1 proteins in relation to tumour development and prognosis in patients with microsatellite stable colorectal cancer
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DOI：
10.14670/hh-23.1495
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发表时间：
2008-12-01
影响因子：
2
通讯作者：
Sun, Xiao-Feng
中科院分区：
文献类型：
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作者：
Gao, Jingfang;Zhang, Hong;Sun, Xiao-Feng
RAD50/Mre11/NBS1复合体是DNA双链断裂修复和维持基因组完整性所必需的。本研究采用免疫组织化学方法检测了Mre11、NBS1和Rad50在原发癌(n=208)、癌旁组织(n=41)、癌旁正常粘膜(n=130)和淋巴结转移癌(n=26)中的表达，并探讨了它们在结直肠癌中的临床病理意义。结果发现，癌组织中mre11和nbs1的表达强度和百分比呈正相关，且与rAD50呈正相关(P<；0.0001)。Mre11、NBS1或RAD50/Mre11/NBS1强阳性表达与MSS、hMLH1阳性表达、肿瘤早期(TNM分期I、II期)及预后相关(P<；0.05)。Mre11的高表达与较少的局部复发和高的细胞凋亡活性有关(P<；0.05)。在MSS-CRC中，Mre11和NBS1的表达强于正常粘膜(P<；0.05)，且NBS1在原发灶中的高表达与TNM分期I、II期患者的预后有关(单因素分析：P=0.03；多因素分析：P=0.07)。在MSI癌组织中，Mre11和NBS1的表达在正常粘膜、原发肿瘤和转移癌之间以及临床病理变量之间均无差异。综上所述，Rad50/Mre11/NBS1蛋白相互作用，在MSS和MSI癌中具有不同的临床病理意义，该复合体的每一组分可能具有额外的作用。NBS1可能是影响TNM I、II期MSS患者预后的一个因素。
RAD50/MRE11/NBS1 complex is essential for DNA double-strand break repair and for maintaining genomic integrity. In this study, we immunohistochemically examined MRE11, NBS1 and RAD50 expression in primary CRCs (n = 208), the corresponding distant (n= 41) and adjacent normal mucosa ( n= 130), and lymph node metastases ( n= 26), and investigated their clinicopathological significance in colorectal cancers ( CRCs). We found that the intensity and percentage of MRE11 and NBS1 in primary CRCs were positively correlated with each other and with RAD50 (P < 0.0001). Strong expression of MRE11, NBS1 or combined RAD50/MRE11/NBS1 was related to MSS, positive hMLH1 expression, earlier tumour stage (TNM stage I and II) and favourable survival (P < 0.05). A high percentage of MRE11 expression was associated with less local recurrence and high apoptotic activity (P < 0.05). In MSS CRCs, the expression of MRE11 and NBS1 was stronger than that in normal mucosa (P < 0.05), and strong expression of NBS1 in primary tumour was related to favourable survival of patients in TNM stage I and II (univariate analysis: P = 0.03; multivariate analysis: P = 0.07). In MSI CRCs, neither MRE11 nor NBS1 expression showed differences among normal mucosa, primary tumour and metastasis, or among clinicopathological variables. In conclusion, RAD50/MRE11/NBS1 proteins interacted with each other, which had different clinicopathological significance in MSS and MSI CRCs, and further, each component of the complex might have additional roles. NBS1 might be a prognostic factor for patients with MSS tumour in TNM stage I and II.