Ubillos Luis, Berriel Edgardo, Mazal Daniel, Victoria Sabina, Barrios Enrique, Osinaga Eduardo, Berois Nora
Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay.
Servicio de Oncología Clínica, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo 11600, Uruguay.
Oncol Lett. 2018 Jul;16(1):225-234. doi: 10.3892/ol.2018.8686. Epub 2018 May 10.
Colorectal carcinoma (CRC) is the second leading cause of cancer mortality worldwide. O-glycosylated mucins at the cell surface of colonic mucosa exhibit alterations in cancer and are involved in fundamental biological processes, including invasion and metastasis. Certain members of the GalNAc-transferase family may be responsible for these changes and are being investigated as novel biomarkers of cancer. In the present study the prognostic significance of GalNAc-T6 was investigated in patients with CRC patients. GalNAc-T6 expression was observed in all three colon cancer cell lines analyzed by reverse transcription-polymerase chain reaction, immunofluorescence and flow cytometry. A cohort of 81 colon cancer specimens was analyzed by immunohistochemical staining using MAb T6.3. It was demonstrated that GalNAc-T6 was expressed in 35/81 (43%) cases of colon cancer but not in the normal colonic mucosa. No association was observed with the clinical-pathologic parameters. However, patients expressing GalNAc-T6 had a significantly increased overall survival (median, 58 months; P<0.001) compared with GalNAc-T6 negative patients, especially those with advanced disease. These results suggest that GalNAc-T6 expression predicts an improved outcome in patients with CRC. The molecular mechanism underlying the less aggressive behavior of colon cancer cells expressing GalNAc-T6 remains to be elucidated.
结直肠癌（CRC）是全球癌症死亡的第二大主要原因。结肠黏膜细胞表面的O-糖基化粘蛋白在癌症中表现出改变，并参与包括侵袭和转移在内的基本生物学过程。N-乙酰半乳糖胺转移酶家族的某些成员可能是这些变化的原因，并且正在作为癌症的新型生物标志物进行研究。在本研究中，对CRC患者中GalNAc-T6的预后意义进行了研究。通过逆转录-聚合酶链反应、免疫荧光和流式细胞术分析，在所有三种结肠癌细胞系中均观察到GalNAc-T6表达。使用单克隆抗体T6.3通过免疫组织化学染色分析了81例结肠癌标本。结果表明，GalNAc-T6在35/81（43%）例结肠癌中表达，但在正常结肠黏膜中不表达。未观察到与临床病理参数的相关性。然而，与GalNAc-T6阴性患者相比，尤其是晚期疾病患者，表达GalNAc-T6的患者总生存期显著延长（中位数，58个月；P<0.001）。这些结果表明，GalNAc-T6表达预示着CRC患者的预后改善。表达GalNAc-T6的结肠癌细胞侵袭性较低的分子机制仍有待阐明。
