Abstract
ObjectivesThis study investigated the PKCα protein expression in gastric carcinoma, and correlated it with clinicopathological parameters. The prognostic significance of PKCα protein expression in gastric carcinoma was analyzed.MethodsQuantitative real-time PCR test was applied to compare the PKCα mRNA expression in tumorous and nontumorous tissues of gastric carcinoma in ten randomly selected cases. Then PKCα protein expression was evaluated in 215 cases of gastric carcinoma using immunohistochemical method. The immunoreactivity was scored semiquantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely PKCα overexpression group with score 2 or 3, and non-overexpression group with score 0 or 1. The PKCα protein expression was correlated with clinicopathological parameters. Survival analysis was performed to determine the prognostic significance of PKCα protein expression in patients with gastric carcinoma.ResultsPKCα mRNA expression was upregulated in all ten cases of gastric carcinoma via quantitative real-time PCR test. In immunohistochemical study, eighty-eight out of 215 cases (41%) of gastric carcinoma revealed PKCα protein overexpression, which was statistically correlated with age (P = 0.0073), histologic type (P<0.0001), tumor differentiation (P = 0.0110), depth of invasion (P = 0.0003), angiolymphatic invasion (P = 0.0373), pathologic stage (P = 0.0047), and distant metastasis (P = 0.0048). We found no significant difference in overall and disease free survival rates between PKCα overexpression and non-overexpression groups (P = 0.0680 and 0.0587). However, PKCα protein overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 0.632, P = 0.0415).ConclusionsPKCα protein is upregulated in gastric carcinoma. PKCα protein expression is statistically correlated with age, histologic type, tumor differentiation, depth of invasion, angiolymphatic invasion, pathologic stage, and distant metastasis. The PKCα protein overexpression in patients with gastric carcinoma is a significant independent prognostic factor in multivariate Cox regression analysis.
Highlights
Gastric cancer is the fourth most common cancer worldwide, and the second leading cause of cancer death in men and the fourth in women [1,2]
PKCa mRNA Expression was Upregulated in Gastric Carcinoma
In all ten tumor and non-tumor pairs of gastric tissues randomly selected for quantitative real-time PCR, the mRNA expression of PKCa in tumor tissues were substantially increased when compared to non-tumor tissues (Table 1)
Summary
Gastric cancer is the fourth most common cancer worldwide, and the second leading cause of cancer death in men and the fourth in women [1,2]. Gastric cancer remains a major public health problem throughout the world. The carcinogenesis of gastric carcinoma is not well understood, but it exhibits a multi-hit process of genetic alterations involving suppressor genes and oncogenes [3,4]. The PKC family members are classified into three major groups: classical (a, b, and c), novel (d, e, g, and h), and atypical (m, l, j). Novel PKCs are activated by phospholipids, and activation of atypical forms occurs independently of calcium or phospholipids. PKCs are involved in various cellular processes including regulating gene expression, proliferation, differentiation, apoptosis, migration, and tumor development [5,6,7,8,9,10]. Because of the existence of many PKC isoforms and their involvement in different cellular signaling pathways, the roles of PKC isoforms in carcinogenesis have not been clarified [8]
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