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首页> 外文期刊>International journal of oncology >Altered expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) during gastric carcinogenesis and its clinical implications on gastric cancer
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Altered expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) during gastric carcinogenesis and its clinical implications on gastric cancer

机译：胃癌发生过程中DNA依赖性蛋白激酶催化亚基（DNA-PKcs）的表达变化及其对胃癌的临床意义

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DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a 465-kDa catalytic subunit of DNA-PK, a DNA repair apparatus. DNA-PKcs has been reported to be a tumor suppressor, but details of its expression in human cancer are controversial. To determine the protein expression and clinical implications of DNA-PKcs in gastric carcinogenesis and cancer progression, we evaluated its expression status by immunohistochemistry in 122 non-neoplastic gastric mucosa samples, and in 115 gastric adenomas and 564 consecutive gastric cancers. In addition, we evaluated the clinicopathologic characteristics of gastric cancers showing altered DNA-PKcs expression, and performed microsatellite instability (MSI) analysis at BAT-26 and frameshift mutation analysis of DNA-PKcs. DNA-PKcs expression was negative in foveolar epithelium of normal gastric mucosal tissues, but was positive in most Helicobacter pylori-associated gastritis, intestinal metaplasia and gastric adenoma tissues. In gastric cancers, negative expression of DNA-PKcs was found in 114 of the 564 (20.2%) cancers and was significantly associated with intratumoral neutrophils, MSI-high (H) phenotype, tumor progression, and poor patient survival (p<0.05). Frameshift mutations of (A)10 mononucleotide repeats in DNA-PKcs were found in 24.3% of MSI-H gastric cancers and these were associated with negative expression of DNA-PKcs. Although patients with MSI-H gastric cancers were found to have a lower risk of lymph node metastasis, gastric cancers harboring the (A)10 mutation of DNA-PKcs were found to have a higher risk of lymph node metastasis. In conclusion, the expression of DNA-PKcs was found to be altered during gastric carcinogenesis and negative DNA-PKcs expression was associated with gastric cancer progression. The (A)10 frameshift mutation of DNA-PKcs in gastric cancers was a target of defective mismatch repair, and was associated with lymph node metastasis.
机译：DNA依赖性蛋白激酶催化亚基（DNA-PKcs）是DNA-PK（一种DNA修复仪器）的465 kDa催化亚基。据报道，DNA-PKcs是一种肿瘤抑制因子，但其在人类癌症中表达的细节尚存争议。为了确定DNA-PKcs在胃癌发生和癌变过程中的蛋白表达及其临床意义，我们通过免疫组织化学在122种非肿瘤性胃黏膜样品，115例胃腺瘤和564例连续胃癌中评估了其表达状态。此外，我们评估了显示改变的DNA-PKcs表达的胃癌的临床病理特征，并在BAT-26进行了微卫星不稳定性（MSI）分析，并对DNA-PKcs进行了移码突变分析。在正常胃粘膜组织的小叶上皮中，DNA-PKcs表达为阴性，但在大多数幽门螺杆菌相关的胃炎，肠化生和胃腺瘤组织中为阳性。在胃癌中，在564例癌症中有114例（20.2％）发现DNA-PKcs阴性，并且与肿瘤内嗜中性粒细胞，MSI高（H）表型，肿瘤进展和患者生存不良密切相关（p <0.05） 。在24.3％的MSI-H胃癌中发现了DNA-PKcs中（A）10单核苷酸重复序列的移码突变，这些突变与DNA-PKcs的负表达有关。尽管发现MSI-H胃癌患者的淋巴结转移风险较低，但发现携带（A）10 DNA-PKcs突变的胃癌的淋巴结转移风险较高。总之，发现DNA-PKcs的表达在胃癌发生过程中发生了改变，并且DNA-PKcs的负表达与胃癌的进展有关。胃癌中DNA-PKcs的（A）10移码突变是有缺陷的错配修复的目标，并且与淋巴结转移有关。

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