LGR5 in Barrett's Esophagus and its Utility in Predicting Patients at Increased Risk of Advanced Neoplasia.
LGR5 in Barrett's Esophagus and its Utility in Predicting Patients at Increased Risk of Advanced Neoplasia.
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Barrett食管中的LGR 5及其在预测晚期肿瘤风险增加的患者中的效用。
DOI：
10.14309/ctg.0000000000000272
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发表时间：
2020-12-22
影响因子：
3.6
通讯作者：
Deshpande V
中科院分区：
文献类型：
--
作者：
Neyaz A;Odze RD;Rickelt S;Nieman LT;Bledsoe JR;Mahadevan KK;Arora K;Jeck WR;Taylor MS;Gala M;Patil DT;Yilmaz OH;Rivera MN;Ting DT;Deshpande V
LGR 5是一种已知的干细胞标志物，其在Barrett食管（BE）和相关肿瘤中的表达知之甚少。本研究的目的是评价BE和相关瘤形成中的LGR 5，并评价其作为进展为晚期瘤形成的潜在生物标志物的效用。我们共评估了137例患者，包括119例BE和18例正常胃食管粘膜使用RNA原位杂交LGR 5的表达，这也包括28个进展和30个非进展。使用手动和自动化平台，使用1个定性和2个定量参数评价LGR 5染色。表面LGR 5表达主要见于高度异型增生（12/18），而低度异型增生（1/8）和非异型增生BE（0/17）（P < 0.0001）。与非异型增生BE相比，低度和高度异型增生显示每例患者LGR 5阳性隐窝的平均数量百分比更高（P < 0.0001），每个细胞LGR 5转录物的平均数量增加（P < 0.0001）。与非进展者相比，每例患者的LGR 5阳性隐窝的平均百分比和每细胞的LGR 5转录物的平均数量在进展者的非异型增生BE中也显著更高（P < 0.0001，P = 0.014）。LGR 5区分进展者和非进展者的敏感性和特异性分别为50%和87%。BE相关的晚期肿瘤显示LGR 5阳性细胞区室的扩大，支持其作为这种疾病的干细胞标志物的作用。定量LGR 5表达和表面上皮反应性是BE进展为晚期肿瘤风险增加的新生物标志物。
The expression of LGR5, a known stem cell marker, is poorly understood in Barrett's esophagus (BE) and related neoplasia. The aim of this study was to evaluate LGR5 in BE and related neoplasia and to evaluate its utility as a potential biomarker of progression to advanced neoplasia. We evaluated total 137 patients, including 119 with BE and 18 with normal gastroesophageal mucosa for expression of LGR5 using RNA in situ hybridization; this also included 28 progressors and 30 nonprogressors. The LGR5 stain was evaluated using 1 qualitative and 2 quantitative parameters, using manual and automated platforms. Surface LGR5 expression was mainly seen in high-grade dysplasia (12/18) compared with low-grade dysplasia (1/8) and nondysplastic BE (0/17) (P < 0.0001). In contrast to nondysplastic BE, low- and high-grade dysplasia showed a higher percentage of mean number of LGR5-positive crypts per patient (P < 0.0001) and an increase in the mean number of LGR5 transcripts per cell (P < 0.0001). The mean percentage of LGR5-positive crypts per patient and the mean number of LGR5 transcripts per cell were also significantly higher in nondysplastic BE from progressor compared with nonprogressor (P < 0.0001, P = 0.014). The sensitivity and specificity of LGR5 for distinguishing progressor from nonprogressor were 50% and 87%, respectively. BE-related advanced neoplasia shows an expansion of the LGR5-positive cellular compartment, supporting its role as a stem cell marker in this disease. Quantitative LGR5 expression and surface epithelial reactivity are novel biomarkers of increased risk of progression to advanced neoplasia in BE.
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影响因子：
50.3
作者：
Quante M;Bhagat G;Abrams JA;Marache F;Good P;Lee MD;Lee Y;Friedman R;Asfaha S;Dubeykovskaya Z;Mahmood U;Figueiredo JL;Kitajewski J;Shawber C;Lightdale CJ;Rustgi AK;Wang TC
通讯作者：
Wang TC
影响因子：
3.7
作者：
Jang BG;Lee BL;Kim WH
通讯作者：
Kim WH
影响因子：
8.8
作者：
Barker, Nick;Rookmaaker, Maarten B.;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
9.8
作者：
Downs-Kelly, Erinn;Mendelin, Joel E.;Goldblum, John R.
通讯作者：
Goldblum, John R.
影响因子：
3.3
作者：
Montgomery, E;Bronner, MP;Washington, K
通讯作者：
Washington, K