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.
Highlights
Cancer is being predicted as a leading cause of deaths based on the latest global cancer statistic report, there are 24.5 million new cancer diagnoses and 9.6 million deaths each year [1]
Some other studies failed to report sufficient data and were excluded. 202 articles remained after scanning the titles and abstracts, and among the 202 studies, 109 were experimental studies only, 2 were excluded for review articles, 38 were excluded for no survival data reported, 19 were excluded for insufficient hazard ratios (HRs) or other data, 2 were excluded because the data is no longer available, and 5 analysis was based on The Cancer Genome Atlas (TCGA) data base
Increased evidence indicated that sine oculis homeobox 1 (SIX1) is involved in multiple process of tumor development and indicated the expression level of SIX1 could be a biomarker for assessing the prognosis in tumors
Summary
Cancer is being predicted as a leading cause of deaths based on the latest global cancer statistic report, there are 24.5 million new cancer diagnoses and 9.6 million deaths each year [1]. The features of most cancers are heterogenous, depends on the treatment response, recurrence, and the cancer metastasis potential. Biomarkers that annotated this different feature in different tumor types. SIX1 Expression Indicates Poor Prognosis and stages, either independently or involved in the current tumor stages can offer deep understandings and help to guide the best clinical treatment, like radical surgery or chemoradiotherapy. This approach was approved by both follow-up data collections and the statistics obtained by cancer patients’ outcome. SIX1 has been verified in promoting cancer progression, accelerating cancer cell metabolism and progression
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