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.

CDK12: A Potent Target and Biomarker for Human Cancer Therapy

“…Moreover, patients with high expression of CDK12 show lower overall survival rates than patients with low expression of CDK12 [75]. They have identified positive correlations of CD8+ cell number and CCL21 (CC-chemokine ligand 21) mRNA expression with CDK12 level [75]. These evidences indicate the involvement of CDK12 in gastric cancer.…”

“…Among these, CDK12 amplification is mainly detected in HER2-positive gastric cancer [74]. Ji et al have shown that high-level expression of CDK12 is detected in gastric tumor samples compared with normal samples [75]. Moreover, patients with high expression of CDK12 show lower overall survival rates than patients with low expression of CDK12 [75].…”

“…Ji et al have shown that high-level expression of CDK12 is detected in gastric tumor samples compared with normal samples [75]. Moreover, patients with high expression of CDK12 show lower overall survival rates than patients with low expression of CDK12 [75]. They have identified positive correlations of CD8+ cell number and CCL21 (CC-chemokine ligand 21) mRNA expression with CDK12 level [75].…”

Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development–Review

“…CDK12 has been implicated in cancer pathology, such as cell invasion, suggesting that aberrant CDK12 expression may have oncogenic properties. Thus, this kinase may become a particularly interesting therapeutic target in prostate [ 128 ], esophageal [ 129 ], gastric [ 130 ], breast [ 131 ], endometrial, bladder, uterine, and ovarian [ 132 ], pancreatic [ 133 ], non-small cell lung cancer [ 134 ], lung adenocarcinoma [ 135 ], and follicular lymphoma [ 136 ]. An increasing number of studies point to the role of CDK12, in cell function and cancer, as an effective strategy to inhibit tumor growth, and its potential clinical use as a biomarker.…”

CCL21 activation of the MALAT1/SRSF1/mTOR axis underpins the development of gastric carcinoma

“…CCL21 is a member of the CC chemokines that has been reported to co-localize the dendritic cells and lymphocytes, emphasizing its promise as a therapeutic target for human solid cancers [ 8 ]. Moreover, CCL21 has been previously documented to be overexpressed in GC [ 9 ], highlighting its potential oncogenic role in this malignancy. However, to date, the potential mechanism by which CCL21 influences GC remains undefined.…”