High Labeling Indices of cdc25B is Linked to Progression of Gastric Cancers and Associated With a Poor Prognosis

Abstract

To clarify the significance of cdc25B, which plays an important physiologic role in regulation of the G2/M check point, in progression of gastric cancer, 125 samples of paraffin-embedded gastric cancers were investigated by immunohistochemistry. In addition, 3 human gastric cancer cell lines were studied to determine the cellular localization of cdc25B by immunohistochemistry and cell fractionation followed by Western blotting. In the cell lines cdc25B was found to be present in both nuclei and cytoplasm, but predominantly in nuclei. High labeling indices of cdc25B in invasion front of gastric cancer was observed in 31 out of 125 cases (24.8%), linked to an advanced depth of cancer invasion (P=0.02), high rates of lymphatic invasion (P=0.03), and lymph node metastasis (P<0.01). Furthermore, the Kaplan-Meier method demonstrated a poor prognosis for cdc25B high labeling indices cases (P=0.02), although multivariate analysis revealed it not to be an independent factor. In conclusion, it seems likely that cdc25B is located predominantly in nuclei when overexpressed and this has some linkage with progression of gastric cancer.

YWHAE silencing induces cell proliferation, invasion and migration through the up-regulation of CDC25B and MYC in gastric cancer cells: new insights about YWHAE role in the tumor development and metastasis process

“…Although our results suggest that the highest level of CDC25B expression seems be important for GC initiation in our population, previous studies described its increased expression associated with advanced tumor stage, deeper invasion, and metastasis in East Asian population [22–24]. As described above, the expression of CDC25B was up-regulated in most of the studied GC samples, despite the invasion or metastasis.…”

Small interfering RNA targeting CDC25B inhibits liver tumor growth in vitro and in vivo

“…Our functional assays further suggest that CDC25B promotes cellular invasion and migration of HCC cells. Consistently, the over-expression of CDC25B in gastric cancer was reported to be associated with advanced stage and deep invasion [ 17 ], and also with high rates of lymphatic invasion and lymph node metastasis [ 38 ]. In another study, CDC25B was more frequently found in patients with deeper tumor invasion and lymph node metastasis in squamous cell carcinomas of the esophagus [ 20 ].…”

The design of novel inhibitors for treating cancer by targeting CDC25B through disruption of CDC25B-CDK2/Cyclin A interaction using computational approaches

“…In view of the role in cell cycle progression, it is apparently that CDC25B is closely related with oncogenesis. The over-expression of CDC25B is often found in numerous human tumors, including lung cancer cells [9], liver tumor cells [10] and stomach cancer cells [11], resulting in an excess of CDK2/Cyclin A activation and accelerating cell proliferation, which is associated with a poor clinical prognosis. Therefore, CDC25B has become an attractive anticancer target [12–14].…”