The expression profile and clinic significance of the SIX family in non-small cell lung cancer.
The SIX family homeobox genes have been demonstrated to be involved in the tumor initiation and progression, but their clinicopathological features and prognostic values in non-small cell lung cancer (NSCLC) have not been well defined. We analyzed relevant datasets and performed a systemic review and a meta-analysis to assess the profile of SIX family members in NSCLC and evaluate their importance as biomarkers for diagnosis and prediction of NSCLC.



This meta-analysis included 17 studies with 2358 patients. Hazard ratio (HR) and 95 % confidence interval (CI) were calculated to represent the prognosis of NSCLC with expression of the SIX family genes. Heterogeneity of the ORs and HRs was assessed and quantified using the Cochrane Q and I2test. Begg's rank correlation method and Egger's weighted regression method were used to screen for potential publication bias. Bar graphs of representative datasets were plotted to show the correlation between the SIX expression and clinicopathological features of NSCLC. Kaplan-Meier survival curves were used to validate our prognostic analysis by pooled HR.



The systematic meta-analysis unveiled that the higher expressions of SIX1-5 were associated with the greater possibility of the tumorigenesis. SIX4 and SIX6 were linked to the lymph node metastasis (LNM). SIX2, SIX3, and SIX4 were correlated with higher TNM stages. Furthermore, the elevated expressions of SIX2, SIX4, and SIX6 predicted poor overall survival (OS) in NSCLC (SIX2: HR = 1.14, 95 % CI, 1.00-1.31; SIX4: HR = 1.39, 95 % CI, 1.16-1.66; SIX6: HR = 1.18, 95 % CI, 1.00-1.38) and poor relapse-free survival (RFS) in lung adenocarcinoma (ADC) (SIX2: HR = 1.42, 95 % CI, 1.14-1.77; SIX4: HR = 1.52, 95 % CI, 1.09-2.11; SIX6: HR = 1.25, 95 % CI, 1.01-1.56).



Our report demonstrated that the SIX family members play distinct roles in the tumorigenesis of NSCLC and can be potential biomarkers in predicting prognosis of NSCLC patients.
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Qian
Q
Liu
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Anping
A
Li
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Yijun
Y
Tian
Department of Geriatric, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Yu
Y
Liu
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Tengfei
T
Li
Department of Geriatric, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Cuntai
C
Zhang
Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Jennifer D
JD
Wu
Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. hanxinwei2006@163.com.
Xinwei
X
Han
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. kmwu@tjh.tjmu.edu.cn.
Kongming
K
Wu
D063646:Carcinogenesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics; D005136:Eye Proteins; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics; D009419:Nerve Tissue Proteins; D011379:Prognosis; D015534:Trans-Activators; D000097607:Homeobox Protein SIX3
D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D000097607:Homeobox Protein SIX3; C099236:SIX1 protein, human; C484762:SIX2 protein, human; C490851:SIX4 protein, human; C106687:SIX5 protein, human; C491945:SIX6 protein, human
Lung cancer; Meta-analysis; Prognosis; SIX family genes; Tumor marker