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J Cancer 2021; 12(13):3827-3840. doi:10.7150/jca.56167 This issue Cite

Research Paper

RECK expression is associated with angiogenesis and immunogenic Tumor Microenvironment in Hepatocellular Carcinoma, and is a prognostic factor for better survival

Zhao-Ru Dong1*, Zhi-Qiang Chen1*, Xiao-Yun Yang2*, Zi-Niu Ding1, Kai-Xuan Liu1, Lun-Jie Yan1, Guang-Xiao Meng1, Ya-Fei yang1, Yu-Chuan Yan1, Sheng-Yu Yao1, Chun-Cheng Yang1, Xu-Ting Zhi1, Tao Li1✉

1. Department of general surgery, Qilu Hospital, Shandong University, Jinan 250012, China.
2. Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, China.
*Co-first authors with equal contributions to this work.

✉ Corresponding author: Tao Li, M.D, PhD, Department of general surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China. Tel & Fax: +86-531-82166651; E-mail: litao7706com.

Citation:
Dong ZR, Chen ZQ, Yang XY, Ding ZN, Liu KX, Yan LJ, Meng GX, yang YF, Yan YC, Yao SY, Yang CC, Zhi XT, Li T. RECK expression is associated with angiogenesis and immunogenic Tumor Microenvironment in Hepatocellular Carcinoma, and is a prognostic factor for better survival. J Cancer 2021; 12(13):3827-3840. doi:10.7150/jca.56167. https://www.jcancer.org/v12p3827.htm
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Abstract

Graphic abstract

Angiogenesis and immunosuppression have been described as closely related processes that can occur in parallel. As an inhibitor of matrix metalloproteinase, whether the level of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in hepatocellular carcinoma (HCC) reflects a link between angiogenesis and immunosuppression is still unknown. We analyzed RNA expression, immune infiltration and survival of HCC from The Cancer Genome Atlas databases. Immune scores and stromal scores were calculated based on the ESTIMATE algorithm to quantify the immune and stromal components in HCC. The association between RECK and clinicopathological features was further investigated by immunohistochemistry on tissue microarray. We found that the prognosis of patients with high RECK expression was significantly better than that of patients with low RECK expression. High RECK expression was associated with high ESTIMATE Score, recruitment of more tumor-infiltrating lymphocytes, low tumor purity, and high PD-L1 expression. In addition, positive RECK expression was associated with a lower incidence of vascular invasion and recurrence, a lower level of alpha fetoprotein (AFP) and microvessel density and a better tumor differentiation. Multivariate analyses revealed that reduced RECK expression was an independent prognostic factor for recurrence and poor prognosis. In conclusion, high RECK expression reflects an immunogenic and hypovascularity status in HCC. RECK is a promising prognostic marker for survival of HCC and may act as a complementary indicator for patients to receive anti-angiogenic therapy or immunotherapy.

Keywords: hepatocellular carcinoma, RECK, angiogenesis, immunotherapy, immune checkpoint inhibitors

Citation styles

APA
Dong, Z.R., Chen, Z.Q., Yang, X.Y., Ding, Z.N., Liu, K.X., Yan, L.J., Meng, G.X., yang, Y.F., Yan, Y.C., Yao, S.Y., Yang, C.C., Zhi, X.T., Li, T. (2021). RECK expression is associated with angiogenesis and immunogenic Tumor Microenvironment in Hepatocellular Carcinoma, and is a prognostic factor for better survival. Journal of Cancer, 12(13), 3827-3840. https://doi.org/10.7150/jca.56167.

ACS
Dong, Z.R.; Chen, Z.Q.; Yang, X.Y.; Ding, Z.N.; Liu, K.X.; Yan, L.J.; Meng, G.X.; yang, Y.F.; Yan, Y.C.; Yao, S.Y.; Yang, C.C.; Zhi, X.T.; Li, T. RECK expression is associated with angiogenesis and immunogenic Tumor Microenvironment in Hepatocellular Carcinoma, and is a prognostic factor for better survival. J. Cancer 2021, 12 (13), 3827-3840. DOI: 10.7150/jca.56167.

NLM
Dong ZR, Chen ZQ, Yang XY, Ding ZN, Liu KX, Yan LJ, Meng GX, yang YF, Yan YC, Yao SY, Yang CC, Zhi XT, Li T. RECK expression is associated with angiogenesis and immunogenic Tumor Microenvironment in Hepatocellular Carcinoma, and is a prognostic factor for better survival. J Cancer 2021; 12(13):3827-3840. doi:10.7150/jca.56167. https://www.jcancer.org/v12p3827.htm

CSE
Dong ZR, Chen ZQ, Yang XY, Ding ZN, Liu KX, Yan LJ, Meng GX, yang YF, Yan YC, Yao SY, Yang CC, Zhi XT, Li T. 2021. RECK expression is associated with angiogenesis and immunogenic Tumor Microenvironment in Hepatocellular Carcinoma, and is a prognostic factor for better survival. J Cancer. 12(13):3827-3840.

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