The Significance of SIX1 as a Prognostic Biomarker for Survival Outcome in Various Cancer Patients: A Systematic Review and Meta-Analysis

Abstract

Sine Oculis Homeobox Homolog 1 (SIX1) is reported to promote cancer initiation and progression in many preclinical models and is demonstrated in human cancer tissues. However, the correlation between SIX1 and cancer patients’ prognosis has not yet been systematically evaluated. Therefore, we performed a systematic review and meta-analysis in various human cancer types and extracted some data from TCGA datasets for further verification and perfection. We constructed 27 studies and estimated the association between SIX1 expression in various cancer patients’ overall survival and verified with TCGA datasets. Twenty-seven studies with 4899 patients are include in the analysis of overall, and disease-free survival, most of them were retrospective. The pooled hazard ratios (HRs) for overall and disease-free survival in high SIX1 expression patients were 1.54 (95% CI: 1.32-1.80, P<0.00001) and 1.83 (95% CI: 1.31-2.55, P=0.0004) respectively. On subgroup analysis classified in cancer type, high SIX1 expression was associated with poor overall survival in patients with hepatocellular carcinoma (HR 1.50; 95% CI: 1.17-1.93, P =0.001), breast cancer (HR 1.31; 95% CI: 1.10-1.55, P =0.002) and esophageal squamous cell carcinoma (HR 1.89; 95% CI: 1.42-2.52, P<0.0001). Next, we utilized TCGA online datasets, and the consistent results were verified in various cancer types. SIX1 expression indicated its potential to serve as a cancer biomarker and deliver prognostic information in various cancer patients. More works still need to improve the understandings of SIX1 expression and prognosis in different cancer types.

Novel LncRNA LINC02936 Suppresses Ferroptosis and Promotes Tumor Progression by Interacting with SIX1/CP Axis in Endometrial Cancer

“…Our study revealed that LINC02936 promotes tumor progression and suppresses ferroptosis in EC by binding to SIX1 and upregulating CP expression. The transcription factor SIX1, a member of the SIX family, is closely associated with the progression of cancer and portends a poor prognosis in various malignancies 53 . SIX1 is also widely involved in tumor metabolism, chemotherapy resistance, and immune escape processes 54 , 55 .…”

SALIQ in Rhabdomyosarcoma: A Repurposed Multidrug Regimen to Augment Standard Treatments by Adding Simvastatin, All Trans Retinoic Acid, Lithium, Itraconazole, and Quercetin

“…SIX1 is highly overexpressed in rhabdomyosarcoma where it forms part of the myocyte maturation block [47][48][49]. SIX1 is upregulated, forming part of the drive to pathologic growth, invasion, and metastasis across a variety of cancers [50][51][52][53]. ATRA reduced SIX1 expression in a myoblast cell line [54].…”

Cytoplasmatic Localization of Six1 in Male Testis and Spermatogonial Stem Cells

“…With the development of bulk RNA sequencing and single cell RNA-sequencing (scRNA-Seq) technology, it is possible to explore gene expression profile of different organs and different cells in one organ (10)(11)(12). The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases show the significant upregulation of Six1 in 13 cancer samples when compared with testicular germ cell tumor (TGCT) (13). We were intrigued by the localization of Six1 in human and mouse stem cells.…”