RNA sequencing analysis reveals protective role of kruppel-like factor 3 in colorectal cancer

Abstract

The Kruppel-like factor (KLF) family of transcription factors plays an important role in embryonic formation and cancer progression. This study was performed to determine the clinical importance of the KLF family in colorectal cancer (CRC). In total, 361 patients with CRC from The Cancer Genome Atlas (TCGA) cohort were used to comprehensively study the role of the KLF family in CRC. The results were then further validated using an in-house cohort (n=194). Univariate and multivariate Cox proportional hazards models were used to assess the risk factors for survival. In the TCGA cohort, KLF3 (hazard ratio [HR], 0.501; 95% confidence interval [CI], 0.272–0.920; P=0.025), KLF14 (HR, 1.454; 95% CI, 1.059–1.995; P=0.020), and KLF17 (HR, 1.241; 95% CI, 1.030–1.494, P=0.023) were identified as potential biomarkers in the univariate analysis, but after Cox proportional hazards analysis, only KLF3 (HR, 0.473; 95% CI, 0.230–0.831; P=0.012) was shown to be independently predictive of overall survival in patients with CRC. This finding was validated in our in-house cohort, which demonstrated that KLF3 expression was an independent predictor of both overall survival (HR, 0.628; 95% CI, 0.342–0.922; P=0.035) and disease-free survival (HR, 0.421; 95% CI, 0.317–0.697, P=0.016). KLF3 expression was inversely correlated with the N stage (P=0.015) and lymphovascular invasion (P=0.020). Collectively, loss of KLF3 was correlated with aggressive phenotypes and poor survival outcomes. KLF3 might be a potential new predictor and therapeutic target for CRC. Further study is needed for a more detailed understanding of the role of KLF3 in CRC.

Transcriptome profiling identified differentially expressed genes and pathways associated with tamoxifen resistance in human breast cancer

“…By comparing the TAMR/MCF-7 cells with the parental cells, transcriptional regulators encoded by LHX and KLF , growth factors encoded by VEGFC, IGF, AGT, TGFA, and HGFAC , cytokines encoded by EDN1 and TIMP2 , G-protein coupled receptor encoded by EDNRA, and transmembrane receptor encoded by BAMBI, enzymes encoded by MYH10 and FLT4, and other genes including LAMA1 and COL, were found to be differentially expressed in our study. Previous studies have shown that the Kruppel-like family of Transcriptional regulators, encoded by KLF genes, regulates not only physiological processes but also the pathogenesis of many diseases, including cancer and inflammatory disorders [ 15 , 16 ]. KLF7, KLF12 and KLF13 were found to be up-regulated in our trascriptome analysis results.…”

A flexible microfluidic system for single-cell transcriptome profiling elucidates phased transcriptional regulators of cell cycle

“…Accordingly, it will now be important to determine how the phased-activity of these novel cell cycle associated transcription factors manifests in the absence of regulation at the level of gene expression. Indeed, the recent findings that levels of ZKSCAN1 modulate hepatocellular carcinoma progression in vivo and in vitro 42 , HES4 expression is linked to osteosarcoma prognosis 43 , and that KLF3 loss correlates with aggressive colorectal cancer phenotypes 44 suggests such understanding could have translational potential. Taken together, our regulon analysis thus confirms, and in several cases extends, understanding of the phase-correlated activity of many transcription factors across cell cycle.…”

“…It will now be important to experimentally dissect the roles and importance of these novel factors to proliferating cells, how their activity is precisely controlled across phases, and determine their roles in disease. Indeed, the aforementioned links between ZKSCAN1 levels and hepatocellular carcinoma 42 , HES4 levels and osteosarcoma 43 , and KLF3 levels with colorectal cancer 44 suggests enhanced understanding of these factors in the context of the cell cycle could have translational potential.…”

Relationship of common variants in Krüppel-like factor 7 gene with susceptibility and prognosis of oral squamous cell carcinoma

“…KLFs are a family of zinc-nger transcription factors, which are widely expressed in multiple human organs or tissues [21]. KLF family is involved in diverse biological processes, and their abnormal expression may lead to human diseases, like cancer [22]. In oral cancer, several members of the KLFs family had been proved to be implicated in the pathogenesis of the cancers.…”