Protein Kinase D1 Correlates with Less Lymph Node Metastasis Risk, Enhanced 5-FU Sensitivity, and Better Prognosis in Colorectal Cancer

Protein Kinase D1 Correlates with Less Lymph Node Metastasis Risk, Enhanced 5-FU Sensitivity, and Better Prognosis in Colorectal Cancer

Bo Huang¹ and Zhuo He¹

¹Gastroduodenal Pancreas Surgery Department, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China

Protein kinase D1 (PKD1) controls tumor growth and invasion of gastrointestinal tract-related cancers, but its prognostic role in colorectal cancer (CRC) is not clear yet. Therefore, this research intended to assess the potential of PKD1 as a marker for CRC patients' management, also to evaluate its effect on 5-fluorouracil (5-FU) chemosensitivity in CRC cell lines. PKD1 protein and mRNA expressions were measured by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction assays in 214 CRC patients, respectively. The PKD1 overexpression plasmids and negative control (NC) plasmids were transfected into the HCT-116 and LoVo cell lines followed by 0-16 µM 5-FU treatment. PKD1 protein (P < 0.001) and mRNA expressions (P < 0.001) were both descended in tumor tissues compared to tumor-adjacent tissues. Meanwhile, tumor PKD1 protein and mRNA expressions were both negatively related to lymph node metastasis, N stage, and tumor-node-metastasis (TNM) stage (all P < 0.05). Prognostically, high expressions of PKD1 protein and mRNA were linked with prolonged disease-free survival (DFS) and overall survival (OS) (all P < 0.05). After adjustment by multivariate Cox analyses, PKD1 mRNA high expression independently forecasted longer DFS [hazard ratio (HR) = 0.199, P = 0.002] and OS (HR = 0.212, P = 0.022). In vitro experiments revealed that PKD1 overexpression decreased the half maximal inhibitory concentration value of 5-FU in the HCT-116 (P = 0.016) and LoVo (P = 0.007) cell lines. PKD1 expression links with less lymph node metastasis risk and satisfied prognosis in CRC patients, which promotes CRC cell chemosensitivity to 5-FU chemosensitivity as well.

Key words —— 5-fluorouracil sensitivity; colorectal cancer; prognosis; protein kinase D1; tumor features

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Tohoku J. Exp. Med., 2023 August, 260(4), 305-314.

Correspondence: Zhuo He, Gastroduodenal Pancreas Surgery Department, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, No. 283, Tongzipo Road, Yuelu District, Changsha, Hunan 410013, China.

e-mail: he87985737@163.com