Expression pattern of CDK12 protein in gastric cancer and its positive correlation with CD8+ cell density and CCL12 expression

Abstract

Background: The aims of this study were to investigate the expression pattern of CDK12 protein in gastric cancer, and to analyze the correlations of CDK12 expression between CD8⁺ cell density and CCL12 expression. Methods: Eighty-six paired tumor and non-tumor samples were collected from patients who underwent radical surgery and had pathological confirmed gastric adenocarcinoma. Immunohistochemistry was used to assess CDK12 expression and CD8⁺ cell density. Expression of CDK12 and CCL21 mRNA was detected by quantitative reverse transcription-polymerase chain reaction. Results: CDK12 expression in gastric tumor tissues was significantly higher than it in paired non-tumor tissues (P<0.001). High expression of CDK12 was identified in 43 cases (50%), and it was significantly correlated with Lauren's classification (diffuse type) and number of metastatic lymph nodes (≥15). High CDK12 protein level indicated a relative poorer overall survival than patients with CKD12 low expression, while it was not identified as an independent prognostic factor. Median number of CD8⁺ cells in tumor tissues was 51 (range: 0-292). Number of CD8⁺ cells was positively correlated with CDK12 expression score in tumor tissues (r=0.243, P=0.024). Positive correlation was also found between CDK12 and CCL21 mRNA expression (r=0.419, P=0.017). Conclusion: High CDK12 expression was detected in gastric cancer which was correlated with malignant phenotypes and worse outcome. Positive correlations of CD8⁺ cell number and CCL21 mRNA expression with CDK12 level were identified.

Keywords: CCL21; CD8+ cells; CDK12; Gastric cancer; lymph node metastasis.

Figure 1

Expression of CDK12 in gastric cancer and survival curve of patients with different CDK12 expression. CDK12 was located in cell nuclear. Expression of CDK12 in non-tumor tissue (A) was lower than its in paired tumor tissue (B). Representative images of CDK12 staining with different score were showed. The intensity scores of image C to F were all 3. The percentage scores were (C) 2; (D) 3; (E) 4; and (F) 5. All images at 400× magnification. G: Patients with CDK12 high expression had a shorter median overall survival than those with CDK12 low expression (40.1 months vs. 50.0 months, P=0.025).

Figure 2

CDK12 expression and CD8⁺ cells in gastric cancer. Positive correlation between CDK12 expression and CD8⁺ cells number was identified in gastric cancer. CDK12 high expression (A) and CD8⁺ cells number over 35 (B) were detected in one gastric tumor sample, while CDK12 low expression (C) and CD8⁺ cells number less than 35 (D) in another tumor sample.

Figure 3

Correlation of CDK12 with number of CD8⁺ cells and CCL21. A: Correlation analysis between CDK12 staining score and number of CD8⁺ cells; B: Correlation analysis between CDK12 and CCL21 mRNA expression.