Gastric cancer (GC) is one of the most common malignant cancers worldwide. However, little is known about the molecular process by which this disease develops and progresses. This study investigated correlations between the expression of nuclear transcription factor SOX4 and various clinicopathologic parameters as well as patients' survival. Expression levels of nuclear SOX4 were analyzed by immunohistochemistry; the data comprised gastric tissues from 168 patients with GC. Paired t tests were used to analyze the differences in nuclear SOX4 expression between tumor and non-tumor tissues from each patient. Two-tailed Χ2 tests were performed to determine whether the differences in nuclear SOX4 expression and clinicopathologic parameters were significant. Time-to-event endpoints for clinicopathologic parameters were plotted using the Kaplan-Meier method, and statistical significance was determined using univariate log-rank tests. Cox proportional hazard model was used for multivariate analysis to determine the independence of prognostic effects of nuclear SOX4 expression. Overexpression of nuclear SOX4 was significantly correlated with depth of invasion (P<0.0001), nodal status (P = 0.0055), distant metastasis (P = 0.0195), stage (P = 0.0003), and vascular invasion (P = 0.0383). Patients who displayed high expression levels of nuclear SOX4 achieved a significantly poorer disease-free survival rate, compared with patients with low SOX4 expression levels (P = 0.003). Univariate Cox regression analysis showed that overexpression of nuclear SOX4 was a clear prognostic marker for GC (P = 0.004). Overexpression of nuclear SOX4 can be used as a marker to predict the outcome of patients with GC.

Colon cancer is one of the most common malignant cancers worldwide but the current therapeutic approaches for advanced colon cancer are less efficient. This study investigated associations between the expression of nuclear transcription factor SOX4 and various clinicopathologic parameters as well as patients’ survival. Expression levels of nuclear SOX4 were analyzed by immunohistochemistry; the data comprised colon tissues from 263 patients with colon cancer. Paired t tests were used to analyze the differences in nuclear SOX4 expression between tumor and non-tumor tissues from each patient. Two-tailed Χ2 tests were performed to determine whether the differences in nuclear SOX4 expression and clinicopathologic parameters were significant. Time-to-event endpoints for clinicopathologic parameters were plotted using the Kaplan-Meier method, and statistical significance was determined using univariate log-rank tests. Cox proportional hazard model was used for multivariate analysis to determine the independence of prognostic effects of nuclear SOX4 expression. Overexpression of nuclear SOX4 was significantly correlated with depth of invasion (P = 0.0041), distant metastasis (P<0.0001), and stage (P = 0.0001). Patients who displayed high expression levels of nuclear SOX4 achieved a significantly poorer disease-free survival rate, compared with patients with low SOX4 expression levels (P<0.001). Univariate Cox regression analysis showed that overexpression of nuclear SOX4 was a clear prognostic marker for colon cancer (P = 0.001). Overexpression of nuclear SOX4 may be used as a marker to predict the outcome of patients with colon cancer.

Although colorectal cancer (CRC) is one of the most common malignancies worldwide, the current therapeutic approaches for advanced CRC are ineffective. In this study, we investigated the involvement of the VAV3 oncogene in tumor progression and in the prognosis of human CRC. The two patient cohorts in this study comprised 354 CRC cases from 1998 to 2005 with documented pathologic and clinical factors and clinical outcomes. VAV3 protein levels were significantly correlated with the depth of invasion (P = 0.0259), the nodal status (P < 0.0001), distant metastasis (P = 0.0354), the stage (P < 0.0001), and poor disease-free survival (P = 0.003). Multivariate Cox regression analysis showed that VAV3 overexpression is an independent prognostic marker for CRC (P = 0.041). In vitro experiments indicated that VAV3 knockdown inhibited CRC cell growth, spread, and xenograft proliferation. Mechanistic studies further revealed that VAV3 overexpression could dysregulate the expression of cell cycle control- and metastasis-related molecules by activating the PI3K-AKT signaling pathway in both CRC cells and xenografts. This study suggests that VAV3 overexpression could be a useful marker for predicting the outcomes of CRC patients and that VAV3 targeting represents a potential modality for treating CRC.

Cyclin‐dependent kinase‐like 2 (CDKL2), a new member of the cyclin‐dependent kinase family, may be involved in gastric cancer (GC) progression. Thus, we conducted this study to explore the clinical effect of CDKL2 in GC. Immunohistochemistry was used to measure CDKL2 levels in gastric tissues. The association of a high CDKL2 level with clinical and pathological characteristics, and the correlation between the CDKL2 level and disease‐free and overall survival were analyzed. Transfection was employed to overexpress CDKL2 in GC cells and to investigate the effect of CDKL2 overexpression on cell proliferation and invasion. Loss of CDKL2 was positively correlated with several clinical and pathological characteristics, and patients with a low CDKL2 level had significantly poorer disease‐free and overall survival than those with a high level (P = .005 and .001, respectively). Univariate analysis using the Cox proportional hazards model indicated that a low CDKL2 level was a prognosticator for inferior disease‐free survival (P = .007). Based on immmunoblotting data, AGS and HGC‐27 GC cells were chosen for CDKL2 overexpression. Cellular studies revealed that CDKL2 overexpression impaired cell proliferation and invasion. Loss of CDKL2 may serve as a biomarker for predicting GC patient outcomes and a potential therapeutic target for GC treatment.

Although gastric cancer (GC) is one of the most common cancers, knowledge of its development and carcinogenesis is limited. To date, expression of ubiquitin‐specific protease 3 (USP3) in all types of cancer, including GC, is still unknown. The present study explored the involvement of USP3 in the carcinogenesis and prognosis of GC. We measured USP3 expression in normal and GC tissues and cell lines. Correlations between USP3 protein level and clinicopathological parameters, as well as the significance of USP3 protein level for disease‐free survival were assessed. Small hairpin RNA technology and transfection were used to investigate the effect of USP3 manipulation on cell proliferation and spreading. Moreover, xenograft proliferation and metastasis were used to explore the influence of USP3 on tumor growth and metastasis in animals. An increase in USP3 expression was observed in GC cells and tissues. The overexpression of USP3 was significantly correlated with several clinicopathological parameters and poor disease‐free survival. Multivariate Cox regression analysis showed that the overexpression of USP3 was an independent prognostic biomarker. Silencing of USP3 suppressed GC cell proliferation and spreading in vitro as well as xenograft proliferation and metastasis in vivo; however, opposite results were obtained when USP3 was overexpressed. Further studies showed that USP3 influenced cell proliferation and spreading by regulating the cell cycle control‐ and epithelial‐mesenchymal transition‐related molecules. This study suggests that USP3 overexpression can be a useful biomarker for predicting the outcomes of GC patients and that USP3 targeting represents a potential modality for treating GC.