Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do, Korea.
PLoS One. 2012;7(12):e52705. doi: 10.1371/journal.pone.0052705. Epub 2012 Dec 20.
Autophagy has paradoxical and complex functions in cancer development, and autophagy-related genes (ATG) are key regulators in autophagy. Until now, more than 30 different ATG proteins have been identified in yeast, and their mammalian counterparts also have been reported. Although the roles of a few ATG proteins in cancer have been characterized, the role of ATG10 is almost completely unknown.
METHODOLOGY/PRINCIPAL FINDINGS: To investigate the clinicopathological role of ATG10 in colorectal cancer, we analyzed ATG10 expression in colorectal cancer tissues and cell lines. Protein expression analysis showed that ATG10 is highly increased in colorectal cancer (tissue - 18/37 cases, 48%; cell line -8/12 cell lines, 66%). Immunohistochemical analysis with clinicopathological features indicated a strong association of the up-regulation of ATG10 with tumor lymph node metastasis (p = 0.005) and invasion (p<0.001). Moreover, both 5-year disease free survival and overall survival rates of patients bearing tumors that did not express ATG10 were significantly higher than those of patients bearing ATG10-expressing tumors (p = 0.012).
CONCLUSION/SIGNIFICANCE: Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis indicating that ATG10 may be a potential prognostic maker in colorectal cancer.
自噬在癌症发展中具有矛盾和复杂的功能，自噬相关基因（ATG）是自噬的关键调节因子。到目前为止，在酵母中已经鉴定出超过 30 种不同的 ATG 蛋白，其哺乳动物对应物也已被报道。尽管已经对几种 ATG 蛋白在癌症中的作用进行了表征，但 ATG10 的作用几乎完全未知。
方法/主要发现：为了研究 ATG10 在结直肠癌中的临床病理作用，我们分析了结直肠癌组织和细胞系中 ATG10 的表达。蛋白表达分析表明，ATG10 在结直肠癌中高度增加（组织-37 例中的 18 例，48％；细胞系-12 种细胞系中的 8 种，66％）。与临床病理特征的免疫组织化学分析表明，ATG10 的上调与肿瘤淋巴结转移（p=0.005）和侵袭（p<0.001）密切相关。此外，不表达 ATG10 的肿瘤患者的 5 年无病生存率和总生存率均明显高于表达 ATG10 的肿瘤患者（p=0.012）。
结论/意义：结直肠癌中 ATG10 的表达增加与血管淋巴管侵犯和淋巴结转移相关，表明 ATG10 可能是结直肠癌的潜在预后标志物。
