AUTHOR=Zheng Kun , Yao Shuo , Yao Wei , Li Qianxia , Wang Yali , Zhang Lili , Chen Xiuqiong , Xiong Huihua , Yuan Xianglin , Wang Yihua , Zou Yanmei , Xiong Hua 

TITLE=Association Between RSK2 and Clinical Indexes of Primary Breast Cancer: A Meta-Analysis Based on mRNA Microarray Data

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.770134

DOI=10.3389/fgene.2021.770134

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Although ribosomal protein S6 kinases, 90 kDa, polypeptide 3 (<italic>RSK2</italic>, <italic>RPS6KA3</italic>) has been reported to play an important role in cancer cell proliferation, invasion, and migration, including breast cancer, its clinical implication in primary breast cancer patients is not well understood, and there were not many studies to explore the relationship between <italic>RSK2</italic> and breast cancer on a clinical level.</p><p><bold>Methods:</bold> A systematic series matrix file search uploaded from January 1, 2008 to November 31, 2017 was undertaken using ArrayExpress and Gene Expression Omnibus (GEO) databases. Search filters were breast cancer, RNA assay, and array assay. Files eligible for inclusion met the following criteria: a) sample capacity is over 100, b) tumor sample comes from unselected patient’s primary breast tumor tissue, and c) expression of <italic>RSK2</italic> and any clinical parameters of patients were available from the files. We use median as the cutoff value to assess the association between the expression of <italic>RSK2</italic> and the clinical indexes of breast cancer patients.</p><p><bold>Finding:</bold> The meta-analysis identified 13 series matrix files from GEO database involving 3,122 samples that come from patients’ primary breast cancer tissue or normal tissue. The expression of <italic>RSK2</italic> in tumor tissues is lower than that in normal tissues [odds ratio (OR), 0.54; 95% credible interval (CI), 0.44–0.67; Cochran’s <italic>Q</italic> test <italic>p</italic> = 0.14; <italic>I</italic><sup>2</sup> = 41.7%]. Patients with a high expression of <italic>RSK2</italic> showed more favorable overall survival [hazard ratio (HR), 0.71; 95% CI, 0.49–0.94; Cochran’s <italic>Q</italic> test <italic>p</italic> = 0.95; <italic>I</italic><sup>2</sup> = 0.0%] and less potential of distant metastasis (OR, 0.59; 95% CI, 0.41–0.87; Cochran’s <italic>Q</italic> test <italic>p</italic> = 0.88; <italic>I</italic><sup>2</sup> = 0.0%) and lymph node infiltration (OR, 0.81; 95% CI, 0.65–0.998; Cochran’s <italic>Q</italic> test <italic>p</italic> = 0.09; <italic>I</italic><sup>2</sup> = 42.8%). Besides, the expression of <italic>RSK2</italic> in luminal breast cancer is lower than Cochran’s <italic>Q</italic> test <italic>p</italic> = 0.06; <italic>I</italic><sup>2</sup> = 63.5%). <italic>RSK2</italic> overexpression corresponded with higher histological grade (OR, 1.329; 95% CI, 1.03–1.721; Cochran’s <italic>Q</italic> test <italic>p</italic> = 0.69; <italic>I</italic><sup>2</sup> = 0.0%). <italic>RSK2</italic> expression is also associated with estrogen receptor (ER) and age.</p><p><bold>Conclusion:</bold> The meta-analysis provides evidence that <italic>RSK2</italic> is a potential biomarker in breast cancer patients. The expression of <italic>RSK2</italic> is distinctive in different intrinsic subtypes of breast cancer, indicating that it may play an important role in specific breast cancer. Further study is needed to uncover the mechanism of <italic>RSK2</italic> in breast cancer.</p><p><bold>Systematic Review Registration:</bold> (website), identifier (registration number).</p>