No abstract

Nanog is a transcription factor that plays key roles in the self‐renewal and maintenance of pluripotency in human embryonic stem (ES) cells. Among Nanog's 11 pseudogenes, NANOGP8 theoretically could be a retrogene, but was considered unlikely as it has not been identified in any expressed sequence tags (ESTs). In this study, we found that NANOGP8 was expressed in several cancer cell lines and in all cancer tissues tested. The complete coding sequence was cloned and the sequence is highly homologous to that of Nanog. We were also able to detect its protein expression using anti‐Nanog antibody in recombinant Escherichia coli and some cancer cell lines tested. In addition, expression of NANOGP8 in NIH3T3 cells can promote cell proliferation. The expression of NANOGP8 in cancer cell lines and cancer tissues suggests that NANOGP8 may play important roles in tumorigenesis. This work not only has potential significance in stem cell and cancer research, but it also raises the possibility that some of the human pseudogenes may have regulatory functions.

Fibroblast growth factor receptors (FGFRs) play key roles in promoting the proliferation, differentiation, and migration of cancer cell. Inactivation of FGFRs by tyrosine kinase inhibitors (TKI) has achieved great success in tumor-targeted therapy. However, resistance to FGFR-TKI has become a concern. Here, we review the mechanisms of FGFR-TKI resistance in cancer, including gatekeeper mutations, alternative signaling pathway activation, lysosome-mediated TKI sequestration, and gene fusion. In addition, we summarize strategies to overcome resistance, including developing covalent inhibitors, developing dual-target inhibitors, adopting combination therapy, and targeting lysosomes, which will facilitate the transition to precision medicine and individualized treatment.

Purpose: The aim of present study was to investigate the methylation and expression status of spleen tyrosine kinase (SYK) in human hepatocellular carcinoma (HCC) and to evaluate this information for its ability to predict disease prognosis. E-cadherin and TIMP-3 methylation was also analyzed here as control because both were associated with poor prognosis in some types of tumors. Experimental Design: We analyzed the methylation status of SYK, E-cadherin, and TIMP-3 in 124 cases of HCC and assessed the correlation of such methylations with clinicopathologic variables and prognosis after tumor resection. Results: We found that SYK, E-cadherin, and TIMP-3 genes were methylated in 27%, 27%, and 42% of HCC neoplastic tissues, respectively. The loss of SYK mRNA or Syk protein expression was highly correlated with SYK gene methylation. The patients with methylated SYK in neoplastic tissues had a significantly lower overall survival rate after hepatectomy than those with unmethylated SYK. No significant difference in overall survival rates, however, was found between groups of patients with methylated and unmethylated E-cadherin or TIMP-3. Patients with negative Syk protein expression had a significantly lower overall survival rate than those with positive Syk protein expression. Multivariate analyses indicated that factors affecting overall survival were tumor-node-metastasis stage, Child-Pugh classification, SYK methylation, or Syk protein status. Conclusions: Our results indicate that SYK methylation and loss of Syk expression in HCC neoplastic tissues are independent biomarkers of poor patient outcome and that determination of SYK methylation or Syk expression status may offer guidance for selecting appropriate treatments.