Research Paper Volume 14, Issue 16 pp 6656—6667
Gene expression profile of human colorectal cancer identified NKTR as a biomarker for liver metastasis
- 1 Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310002, Zhejiang, China
- 2 Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China
- 3 Cancer Center, Zhejiang University, Hangzhou 310058, Zhejiang, China
- 4 Department of Medical Oncology, Institute of Cancer and Basic (Medicine ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou 310022, Zhejiang, China
- 5 Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Received: June 30, 2020 Accepted: July 21, 2021 Published: August 23, 2022
https://doi.org/10.18632/aging.204242How to Cite
Copyright: © 2022 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objective: Liver metastasis is one of the prognostic factors of colorectal cancer (CRC). The aim of this study is to identify biomarkers that facilitate easier detection of liver metastasis.
Methods: Significance Analysis of Microarrays (SAM) and Array Data Analyzer (ADA) were applied used for the analysis of differentially differently expressed mRNAs. mRNA expression was verified by quantitative real-timer reverse transcriptiontase polymerase chain reaction (qRT-PCR). Immunohistochemistry were was used to show natural killer-tumor recognition (NKTR) expression in CRC. NKTR-knockdown CRC cells were constructed obtained by using short hairpin RNA (shRNA). Followed by CCK-8 assay, plate colony formation test, and transwell assay were used to evaluate the influence of NKTR on cell proliferation, migration, and invasion in vitro.
Results: SAM yielded showed 256 up-regulated and 224 down-regulated differentially differently expressed genes. Seven genes were identified by using ADA, tools and four genes were verified by using qRT-PCR. Three genes (metastasis associated lung adenocarcinoma transcript 1 (MALAT1), nuclear factor I/B (NKTR), and nuclear factor I/B (NFIB)) showed a statistically significant considerabley difference between CRC with and liver metastasis and CRC without liver metastasis. Immunohistochemical analysis showed that NKTR expression was much lower in primary CRC with liver metastasis than that in primary CRC without liver metastasis. The NKTR protein plays a role in the lytic function of natural killer (NK) cells and it has been rarely studied in the CRC. The down-regulation of NKTR by shRNA interference in CRC cells increased cell proliferation, migration, and invasion in vitro.
Abbreviations
CRC: colorectal cancer; SAM: significance analysis of microarrays; ADA: array data analyzer; qRT-PCR: quantitative real-time reverse transcriptase polymerase chain reaction; IHC: immunohistochemistry; CT: computerized tomography; NKTR: natural killer-tumor recognition; MALAT1: metastasis associated lung adenocarcinoma transcript 1; NFIB: nuclear factor I/B; HNRPDL: heterogeneous nuclear ribonucleoprotein D like; HNRPA2B1: heterogeneous nuclear ribonucleoprotein A2/B1; SFPQ: splicing factor proline and glutamine rich; CROP: LUC7 like 3 pre-mRNA splicing factor.