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C-X-C chemokine receptor 4 and Notch1 have been shown to play oncogenic role individually. This study aimed to determine the combinatorial role of C-X-C chemokine receptor 4 and Notch1 in lung adenocarcinoma. Expression of C-X-C chemokine receptor 4 and Notch1 was detected in resected tumor samples from 185 patients with lung adenocarcinoma at stage I-IIIa by immunohistochemistry. Correlations of their immunoscores with clinicopathological characteristics and disease-specific survival were retrospectively investigated. A three-dimensional capillary-like sprouting model was established to assess the effects of C-X-C chemokine receptor 4 and Notch1 on angiogenesis in vitro. The results revealed that expression of C-X-C chemokine receptor 4 and Notch1 was elevated in lung adenocarcinoma tissues. The high co-expression of C-X-C chemokine receptor 4 and Notch1 was significantly correlated with tumor size, tumor status, nodal status, tumor stage, and lymphovascular invasion, as well as decreased disease-specific survival. Multivariate analysis showed that lymphovascular invasion (hazard ratio: 0.205, 95% confidence interval: 0.086-0.491, p < 0.0001) and co-expression of C-X-C chemokine receptor 4 and Notch1 (hazard ratio: 0.293, 95% confidence interval: 0.168-0.510, p < 0.0001) were independent indicators of poor prognosis in lung adenocarcinoma. Furthermore, Notch1 enhanced the effects of C-X-C chemokine receptor 4 to promote angiogenesis by regulating Flt1 and Flt4 in vitro. In conclusion, co-expression of C-X-C chemokine receptor 4 and Notch1 is associated with tumor progression and lymphovascular invasion and is an independent indicator of poor survival in lung adenocarcinoma. In lung adenocarcinoma patients with high C-X-C chemokine receptor 4 and Notch1 expression, simultaneous inhibition of both factors might be an effective treatment strategy.

Citation

Zhuangzhuang Cong, Haiwei Wu, Zhong Guo, Tao Qin, Yang Xu, Hua Jing, Yanqing Wang, Yi Shen. High expression of C-X-C chemokine receptor 4 and Notch1 is predictive of lymphovascular invasion and poor prognosis in lung adenocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2017 Jun;39(6):1010428317708698

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PMID: 28618922

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