Protein kinase D1 mRNA level may predict cancer-specific survival in heavy smokers with esophageal squamous cell cancers

Abstract

Protein kinase D1 (PRKD1) is a kinase that regulates various pathways, which involve in cell proliferation, apoptosis, cell adhesion and invasion. Although PRKD1 expression has been observed in many cancers, its role in esophageal squamous cell cancer (ESCC) has not been well reported. As its dysregulation in cancers is organ specific, we sought to investigate the potential role of PRKD1 in the progression of ESCC. Samples were collected from 178 patients with completely resected ESCCs at Sun Yat-sen University Cancer Center, including 47 pairs of tumorous and non-tumorous tissues. PRKD1 mRNA expression was investigated by quantitative real-time polymerase chain reaction. Receiver operating characteristic (ROC) curve analysis was used to search for a feasible cut-off point of PRKD1 mRNA levels for predicting cancer-specific survival. Kaplan-Meier and multivariate Cox regression analysis were used to assess the prognostic value of PRKD1 mRNA level in ESCC patients. In result, upregulation of PRKD1 mRNA was detected in 55.3% (26/47) of ESCC tissues compared with paired non-tumorous ones (P = 0.011). ROC analysis indicated 3.28 as a cut-off point, and thus 72 and 106 tumors with low and high PRKD1 mRNA expression were categorized. High-PRKD1 mRNA expression in tumors appeared with more frequency in heavy smokers (P = 0.002) and patients with advanced pathological T category (P = 0.034). Kaplan-Meier analysis indicated that patients with low-PRKD1 mRNA had a longer cancer-specific survival than the ones with high-PRKD1 level (P = 0.044). Multivariate analysis showed that tumorous PRKD1 mRNA expression was an independent prognostic factor (hazard ratio: 1.538, 95% confidence interval: 1.018-2.323, P = 0.041) in resected ESCC. Subgroup analysis revealed that the discernibility of PRKD1 mRNA level on ESCC outcomes was only pronounced in heavy smokers (P = 0.002), but not in non-heavy smokers (P = 0.870). PRKD1 might play a potential oncogenic role in ESCC. It might be an independent biomarker to predict prognosis in heavy smokers with ESCC.

Protein kinase D1 regulates ERα‐positive breast cancer cell growth response to 17β‐estradiol and contributes to poor prognosis in patients

“…Finally, we showed that PKD1 expression does not correlate with classical clinical and pathological prognostic factors (SBR histological grade, macroscopic tumour size, PR and ERBB2 statuses and PIK3CA mutation status). This interesting point suggests that PKD1 may also represent a novel attractive independent prognostic factor in breast cancer as recently described for esophageal squamous and laryngeal cancers.…”

Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin

“…This may provide an as yet unknown link between DDX3X and ARID1A , at least in terms of how promoter swapping may activate PRKD1 in these tumors. The PRKD1 gene encodes a kinase that has previously been implicated in colorectal, breast, esophageal, laryngeal, and other cancers, although deletion and/or gene silencing appear to be the mechanisms associated with colorectal and breast cancers (Borges et al, ; Brim et al, ), while activation is associated with esophageal and laryngeal cancers (Fountzilas et al, 2014; Xie et al, ). Along with the related PRKD2 and PRKD3 genes, it is associated with signal transduction in the diacylglycerol (DAG) and protein kinase C (PKC) pathway.…”

“…Along with the related PRKD2 and PRKD3 genes, it is associated with signal transduction in the diacylglycerol (DAG) and protein kinase C (PKC) pathway. When activated PRKD family of kinases have a role in signal transduction, trafficking, migration, differentiation and proliferation (Xie et al, ) and potentially may serve as targets for future drug therapies. Further studies are required to elucidate the mechanism of PRKD gene activation in these tumors and how this leads to tumor proliferation.…”

Positive cross talk between protein kinase D and β-catenin in intestinal epithelial cells: impact on β-catenin nuclear localization and phosphorylation at Ser552

“…For example, PRKD1 gene expression is increased in subpopulations of cancers of the colon, liver, and upper aero-digestive system, as revealed by searching COSMIC (catalog of somatic mutations in cancer). Recently, high PKD1 mRNA levels have been linked to lower cancer-specific survival in heavy smokers with esophageal squamous cell cancers (74) and predicts recurrence in laryngeal cancer (12). Indeed, the level of PRKD1 expression has been proposed as a laryngeal cancer prognostic marker for routine clinical applications.…”