GATA2 rs2335052 Polymorphism Predicts the Survival of Patients with Colorectal Cancer

<div><p>Background</p><p>GATA binding protein 2 (GATA2) is a transcription factor that has essential roles in hematologic malignancies and progression of various solid tumors. Our previous studies suggested that high GATA2 expression is associated with recurrence of colorectal cancer (CRC). However, the influence of GATA2 single nucleotide polymorphisms (SNPs) on the survival of CRC remains unknown.</p><p>Methods</p><p>We genotyped GATA2 SNP rs2335052 using Sanger sequencing after PCR amplification, and determined GATA2 expression by immunohistochemistry in a cohort of 180 CRC patients. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the association between the GATA2 rs2335052 genotypes and the clinical outcome of CRC.</p><p>Results</p><p>We found that there was no significant correlation between the rs2335052 genotypes and the expression of GATA2. However, the Kaplan-Meier survival analysis suggested that the carriers of the A-allele of SNP rs2335052 were significantly associated with increased risk of recurrence and reduced disease-free survival (DFS), compared with those carrying the variant genotype of GG in rs2335052 (<i>P</i> = 0.021). Moreover, univariate and multivariate Cox regression analyses revealed that GATA2 SNP rs2335052 was an independent risk factor for the DFS of CRC patients.</p><p>Conclusion</p><p>Our results demonstrated that GATA2 SNP rs2335052 is an independent predictor for prognosis of CRC patients. This raised the possibility that SNP rs2335052 may serve as a potential indicator for predicting recurrence of CRC after curative colectomy.</p></div

Sequencing results of GATA2 rs2335052 genotypes.

<p>Sequencing results of GATA2 rs2335052 genotypes.</p

Univariate and multivariate analyses of GATA2 rs2335052 genotypes in CRC patients with respect to DFS.

<p><i>HR</i> hazard ratio, <i>CI</i> confidence interval, <i>P</i> values in bold were statistically significant.</p><p>Univariate and multivariate analyses of GATA2 rs2335052 genotypes in CRC patients with respect to DFS.</p

Clinicopathological features with respect to determined genotypes of included GATA2 SNP rs2335052.

<p>Differences in categorical study variables between genotypes were tested for statistical significance with the Chi-squared test. Tumors were classified according to the guidelines of the American Joint Committee on Cancer (AJCC) staging system.</p><p>Clinicopathological features with respect to determined genotypes of included GATA2 SNP rs2335052.</p

Kaplan-Meier analysis for DFS according to rs2335052 genotypes in CRC patients stratified by clinical stage.

<p>Kaplan-Meier curves indicated DFS for the subgroup of patients with stage I/II <b>(A)</b>, and stage III/IV <b>(B)</b> CRC. The log-rank test was used to calculate <i>P</i> values.</p

Immunohistochemical analysis of GATA2 expression in colorectal tissues.

<p>Representative image indicated strong GATA2 staining in CRC tissue, and negative GATA2 staining in matched noncancerous tissue. Magnification is 100×.</p

Kaplan-Meier analysis of DFS according to GATA2 expression.

<p><b>(A)</b> Kaplan-Meier survival curve showed DFS for patients with GATA2-high tumors versus patients with GATA2-low tumors. Kaplan-Meier survival curves showed DFS for patients stratified by GATA2 rs2335052 GG <b>(B)</b>, and GG+AA <b>(C)</b> genotypes. The log-rank test was used to calculate <i>P</i> values.</p

Additional file 2: of STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer

Figure S1. Overexpression or knockdown of GOLPH3 had little effects on STK25 protein levels. a GOLPH3 overexpression had little effects on STK25 protein levels in CRC cells. b knockdown of GOLPH3 had slightly effects on STK25 protein levels in CRC cells. (TIF 1182 kb

Additional file 1: of STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer

Table S1. Sequences of primers. (DOCX 18 kb

Additional file 4: of STK25-induced inhibition of aerobic glycolysis via GOLPH3-mTOR pathway suppresses cell proliferation in colorectal cancer

Figure S3. Rapamycin impaired glycolysis. Rapamycin inhibited glucose consumption (a) and lactate production (b) in LoVo cells. (TIF 881 kb