The Significance of Serum S100A9 and TNC Levels as Biomarkers in Colorectal Cancer.

Purpose: The aim of this study was to evaluate the diagnostic value of S100A9 and tenascin-c (TNC) levels as colorectal cancer (CRC) biomarkers in several ways, including through screening tests, differentiation tests, combination with existing biomarkers (CEA and CA19-9), and serum level measurements before and after surgery. Materials and Methods: In this case-control study, S100A9 and TNC serum levels were measured in 460 participants: 258 CRC patients, 99 patients with benign colonic disease (BCD) and 103 healthy donors (HD). Results: The serum levels of S100A9 were 22.32 (14.88-29.55) ng/ml, 10.02 (5.83-14.15) ng/ml and 10.05 (7.68-15.34) ng/ml in the CRC, BCD and HD groups, respectively. The serum levels of TNC were 4.30 (2.12-6.04) ng/ml, 1.60 (1.06-2.30) ng/ml and 2.00 (1.37-3.00) ng/ml in the CRC, BCD and HD groups, respectively. Significantly higher levels of both biomarkers (S100A9 and TNC) were found in CRC patients (both p<0.001). Both S100A9 and TNC levels were superior to CEA and CA19-9 levels as CRC diagnostic biomarkers; the combination of S100A9, TNC and CEA levels was an excellent biomarker with 79.8% sensitivity and 89.6% specificity. The serum levels of S100A9 and TNC in CRC patients were significantly lower after surgery than before surgery (p<0.01). Conclusion: S100A9 and TNC levels could serve as diagnostic biomarkers of colorectal cancer.

Quantitative proteomic profiling of tumor-associated vascular endothelial cells in colorectal cancer.

To investigate the global proteomic profiles of vascular endothelial cells (VECs) in the tumor microenvironment and antiangiogenic therapy for colorectal cancer (CRC), matched pairs of normal (NVECs) and tumor-associated VECs (TVECs) were purified from CRC tissues by laser capture microdissection and subjected to iTRAQ-based quantitative proteomics analysis. Here, 216 differentially expressed proteins (DEPs) were identified and used for bioinformatics analysis. Interestingly, these proteins were implicated in epithelial mesenchymal transition (EMT), ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, angiogenesis and HIF-1 signaling pathway, which may play important roles in CRC angiogenesis. Among these DEPs we found that Tenascin-C (TNC) was upregulated in TVECs of CRC and correlated with CRC multistage carcinogenesis and metastasis. Furthermore, the reduction of tumor-derived TNC could attenuate human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation through ITGB3/FAK/Akt signaling pathway. Based on the present work, we provided a large-scale proteomic profiling of VECs in CRC with quantitative information, a certain number of potential antiangiogenic targets and a novel vision in the angiogenesis bio-mechanism of CRC.

The Radiosensitization of Sodium Glycididazole on Nasopharyngeal Carcinoma Cells via Enhancing DNA Damage and Promoting Apoptosis.

Background: The radioresistance of nasopharyngeal carcinoma (NPC) was the main cause of radiotherapy failure and it was still a challenge in the treatment of advanced NPC patients. Previous clinical studies demonstrated that sodium glycididazole(CMNA) can enhance the radiosensitivity of NPC, but the corresponding cellular mechanisms or processes remains largely unclear. Methods: To clarify the radiosensitizing effects of CMNA on NPC cells and reveal its cellular mechanisms, its effect on cell survival of NPC cells was assessed by MTT and clonogenic assay, with or without radiation. The potential cellular mechanisms such as cell cycle distribution, apoptosis and DNA damage were assessed. A retrospective analysis of the outcome of patients with III-IV stage NPC who undergo same radiochemotherapy with or without concurrent CMNA treatment was performed to elucidate the role of CMNA in the improvement of the curative effects. Results: The treatment with CMNA at the concentration lower or close to the clinical dosage had little effect on cell survival, cell cycle distribution and a weak effect on DNA damage and cell apoptosis of NPC cells. The combination of CMNA and radiation significantly increased the DNA damage and enhanced the apoptosis of NPC cells, but did not significantly alter the cell cycle distribution as compared with the irradiation (IR) alone. A total of 99 patients who underwent radiochemotherapy were categorized into those with (treatment group, n=52) and without (control group, n=47) the treatment with CMNA. The complete response rates of patients in treatment group were significantly higher than in control group. Conclusions: Our results suggested that CMNA enhance the sensitivity of the NPC cells to radiation via enhancing DNA damage and promoting cell apoptosis. It provides clues for further investigation of the molecular mechanism of the radiosensitization of CMNA on NPC cells.