An immunohistochemical study of cyclin-dependent kinase 5 (CDK5) expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC): a possible prognostic biomarker

Abstract

BackgroundCyclin-dependent kinase 5 (CDK5) is an atypical CDK which plays a vital role in several cancers via regulating migration and motility of cancer cells. However, the clinicopathological impact and function of CDK5 in lung cancer remain poorly understood. The present study was aimed at exploring expression and clinicopathological significance of CDK5 in lung cancer.MethodsThere were 395 samples of lung tissue including 365 lung tumors (339 non-small cell lung cancers and 26 small cell lung cancers) and 30 samples of normal lung. CDK5 expression was detected by immunohistochemistry on lung tissue microarrays.ResultsOver expression was detected in lung cancer compared with normal lung tissues (P = 0.001). Furthermore, area under curve (AUC) of receiver operating characteristic (ROC) of CDK5 was 0.685 (95 % CI 0.564~0.751, P = 0.004). In lung cancer, we also discovered close correlations between CDK5 and pathological grading (r = 0.310, P < 0.001), TNM stage (r = 0.155, P = 0.003), and lymph node metastasis (r = 0.279, P < 0.001) by using Spearman analysis. In two subgroups of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the expression of CDK5 was also higher than that of normal lung tissue, respectively (P = 0.001 and P = 0.004). Moreover, in NSCLCs, Spearman analysis revealed that expression of CDK5 was correlated with TNM stages (r = 0.129, P = 0.017), lymph node metastasis (r = 0.365, P < 0.001), and pathological grading (r = 0.307, P < 0.001), respectively. The significant correlation was also found between CDK5 expression and TNM stages (r = 0.415, P = 0.049) and lymphatic metastasis (r = 0.469, P = 0.024) in SCLCs.ConclusionsThe results of this present study suggest that the CDK5 expression is associated with several clinicopathological factors linked with poorer prognosis.

The Emerging Role of Cdk5 in Cancer

“…Second, mRNA and protein expression levels of Cdk5 and its activators are increased, or decreased, in several forms of cancer and these alterations are correlated with cancer severity (Figure 1a, Key Figure; Table 1). For example, Cdk5 and p35/p25 are elevated in pulmonary neuroendocrine cancers [9–11], in sporadic and familial forms of medullary thyroid carcinoma (MTC) [12] and pituitary adenoma [13]. In fact Cdk5 and p35/p25 expression appear to typify neuroendocrine cancer pathology.…”

CDK5 inhibition in�vitro and in vivo induces cell death in�myeloma and overcomes the obstacle of bortezomib resistance

“…Previous studies showed that aberrant expression of CDK5 had been observed in multiple human cancers, but not in normal tissues. CDK5 were positively correlated with lymph node metastasis and the stage of disease in head and neck squamous cell carcinoma, cervical lesions, lung cancer, hepatocellular carcinoma and nasopharyngeal carcinoma (5)(6)(7)(8)(9)(10), and its overexpression was also associated with the poor prognosis in colorectal cancer and breast cancer (7,8). Tumor tissues with high expression of cdK5 are usually insensitive to chemoradiotherapy and targeted therapy (11,12).…”

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

“…8 Cyclin-dependent kinase 5 was first recognized as a neuron-specific CDK due to the majority distribution of CDK5 activators residing within neurons. 16 However, emerging evidence shows CDK5 might have additional roles in gene expression, cell migration, apoptosis, and pathological processes, leading to inflammation, diabetes, immune dysfunction, and cancer [17][18][19][20][21][22] (Table 1).…”