NEK7 Promotes Pancreatic Cancer Progression And Its Expression Is Correlated With Poor Prognosis.

Zilong Yan,Qirui Lin,Fengmin Lu,Zewei Lin,Zhangfu Li,Weihua Yin,Guangyin Yu,Yanze Su,Jianhua Qu,Jing Yi,Jikui Liu

doi:10.3389/fonc.2021.705797

Abstract

The prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is still dismal. Elucidation of associated genomic alteration may provide effective therapeutic strategies for PDAC treatment. NIMA-related protein kinase 7 is widely expressed in various tumors, including breast cancer, colorectal cancer and lung cancer, and promotes the proliferation of liver cancer cells in vitro and in vivo. We investigated the protein expression level of NEK7 in tumor tissues and adjacent normal tissues using immunohistochemistry of 90 patients with PADC. Meanwhile, the RNA expression level of NEK7 was examined using database-based bioinformatic analysis. Correlation and significance of NEK7 expression with patient clinicopathological features and prognosis were examined. Cell proliferation, cell adhesion, migration and invasion capabilities were measured following downregulation of NEK7 expression. 3D tumor organoids of pancreatic cancer were established and splenic xenografted into nude mice, then liver metastatic ability of NEK7 was evaluated in following 4 weeks. We observed NEK7 expression was upregulated in tumor tissues compared to normal tissues at both RNA and protein levels using bioinformatic analysis and immunohistochemistry analysis in PDAC. NEK7 expression was undetectable in normal pancreatic ducts; NEK7 was overexpressed in primary tumor of PDAC; NEK7 expression was highly correlated with advanced T stage, poorly differentiated histological grade invasive ductal carcinoma, and lymphatic invasion. Meanwhile, patients with higher NEK7 expression accompanied by worse survival outcome. Moreover, NEK7 promoted migration, invasion, adhesion, proliferation and liver metastatic ability of pancreatic cancer cells. Taken together, our data indicate that NEK7 promotes pancreatic cancer progression and it may be a potential marker for PDAC prognosis.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death with a poor 5-year survival rate less than 10% [1]
We found NEK7 expression was significantly upregulated in tumor tissues compared to tumoradjacent normal tissues using bioinformatic analysis (Figure 2B); NEK7 overexpression was accompanied by poorly histological grade of pancreatic ductal adenocarcinoma (PDAC) (Figure 2C); Consist with our bioinformatic results, NEK7 upregulation was correlated with worse prognosis of patients with PDAC in ICGC (International Cancer Genome Consortium) database (Figure 2D)
We examined NEK7 expression pattern in PDAC and investigated its functional effect on pancreatic cancer progression

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death with a poor 5-year survival rate less than 10% [1]. The NIMA related protein kinase family is involved in regulating cell cycle and mitotic progression [7,8,9]. Of these NEK family members, NEK7 is the smallest protein, composed of only a catalytic domain with a 30–40 amino acid N-terminal extension, which shares more than 85% sequence identity to NEK6 [10, 11]. NEK7 is significantly increased in squamous cell carcinoma of the head and neck [25], breast cancer [26], colorectal cancer and lung cancer [27], and promotes the proliferation of liver cancer cells in vitro and in vivo, due to its significant relationship with Ki67 expression in HCC tissues [28].

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Conclusion