Lgr5High/DCLK1High phenotype is more common in early stage and intestinal subtypes of gastric carcinomas
Lgr5High/DCLK1High phenotype is more common in early stage and intestinal subtypes of gastric carcinomas
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DOI：
10.3233/cbm-170383
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发表时间：
2017-01-01
影响因子：
3.1
通讯作者：
Madjd, Zahra
中科院分区：
文献类型：
--
作者：
Kalantari, Elham;Lari, Mohammad Hossein Asadi;Madjd, Zahra
背景：胃癌是世界上第三大常见恶性肿瘤，也是癌症死亡的主要原因之一。肿瘤干细胞（cancer stem cells，CSC）是具有自我更新和分化能力的肿瘤细胞亚群，可能与胃癌的发生、复发、转移和化疗/放疗耐药有关。目的：本研究旨在探讨CSC标志物Lgr 5和DCLK 1在胃癌中的表达模式及其临床病理意义。采用组织芯片（TMA）检测了一系列明确的胃癌组织中Lgr 5和DCLK 1的表达水平，包括75例（80%）肠型胃癌和19例（20%）弥漫型胃癌。结果：Lgr 5和DCLK 1主要在肠型胃癌中表达高于弥漫型胃癌（P = 0.005和P = 0.050）; Lgr 5和DCLK 1在高分化胃癌中的表达明显高于低分化胃癌（P < 0.001和P = 0.007）。联合分析显示Lgr 5和DCLK 1的共表达（Lgr 5（High）/DCLK 1（High））在肠型胃癌（P = 0.025）和高分化胃癌（P < 0.001）中更为常见。结论：Lgr 5（High）/DCLK 1（High）表达模式可能是胃癌肠型的标志性表型。
BACKGROUND: Gastric carcinoma is the third most common malignancy and is one of the main causes of cancer deaths worldwide. Cancer stem cells (CSCs) are a subpopulation of tumour cells capable of self-renewal and differentiation, likely responsible for the initiation, recurrence, metastasis and chemo/radio-resistance.OBJECTIVE: This study was conducted to evaluate the expression patterns and clinicopathologic significance of putative CSC markers, Lgr5 and DCLK1, in gastric carcinoma.METHOD: The expression levels of Lgr5 and DCLK1 were examined in a well-defined series of gastric carcinoma tissues, including 75 (80%) from intestinal and 19 (20%) from diffuse subtypes, using tissue microarray (TMA). In addition, the correlation of the expression of these markers with clinicopathological factors was explored.RESULTS: Higher expressions of Lgr5 and DCLK1 were mainly detected in intestinal subtypes of gastric carcinomas compared to diffuse subtypes (P = 0.005 and P = 0.050, respectively). We also found a higher expression of Lgr5 and DCLK1 more frequently in well-differentiated gastric carcinoma cases (P < 0.001 and P = 0.007). The combined analysis demonstrated that the co-expression of Lgr5 and DCLK1 (Lgr5(High)/DCLK1(High)) was more common in intestinal subtypes (P = 0.025) and well-differentiated gastric carcinoma samples (P < 0.001). Interestingly, there was a significant correlation between Lgr5(High)/DCLK1(High) phenotype and early-stage gastric carcinoma specimens (P = 0.045).CONCLUSION: Our findings indicated that the Lgr5(High)/DCLK1(High) expression pattern may be considered as a signature phenotype for intestinal subtypes of gastric carcinoma.