RESUMEN
The present study aimed to identify whether CD166 can be used as a biomarker for predicting the response of nasopharyngeal carcinoma (NPC) to radiotherapy. The serum concentration of CD166 in patients with NPC were detected by enzyme-linked immunosorbent assay. The secreted level of CD166 with radioresistant NPC was significantly higher than that with radiosensitive NPC. In vitro, the CD166 positive rate in the CNE2 cell membrane was significantly lower than that in the CNE2R cell membrane. The magnetic-activated cell sorting technology was used to obtain CNE-2R-CD166(+) and CNE-2R-CD166(-) cell lines. Then radiosensitivity, cell proliferation, and apoptosis were assessed using colony formation assay, cell counting kit 8 assay (CCK-8), and flow cytometry, respectively. The radiation sensitivity ratio was 1.28, indicating that the CNE2R-CD166(-) cells had a stronger radiation sensitivity. The result of CCK-8 assay indicated that the survival fraction of CNE2R-CD166(+) cells was significantly higher than that of CNE2R-CD166(-) cells. The apoptotic rate of CNE2R-CD166(+) cells was significantly lower than that of CNE2R-CD166(-) cells. Our data demonstrate that the secreted protein CD166 may be can used as a biomarker for predicting the response of NPC to radiotherapy.
RESUMEN
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality worldwide. Mitochondrial dysfunction has been postulated to render cancer cells resistant to apoptosis based on the Warburg hypothesis. However, few studies have investigated the prognostic value of mitochondrial DNA (mtDNA) content and G10398A polymorphism in NSCLC patients. mtDNA copy number and G10398A polymorphism in 128 NSCLC tissue samples were assessed by real-time PCR (RT-PCR) and PCR-RFLP respectively, and their relationship to prognosis were analyzed by survival analysis and Cox proportional hazards model. In vitro, an mtDNA deletion A549 ρ(0) cell model was utilized to assess the function of mtDNA on radiosensitivity. Cell cycle distribution and reactive oxygen species (ROS) were analyzed to elucidate the potential mechanisms. For the whole group, the median follow-up time and overall survival time were 22.5 and 23.4 months, respectively. Patients with high mtDNA content had a marginally longer survival time than patients with low mtDNA content (P=0.053). Moreover, patients with high mtDNA content plus 10398G had a significantly longer overall survival time compared with those having low mtDNA content plus 10398A (47 vs. 27 months, P<0.05). In addition, multivariate analysis showed that stage and low mtDNA content plus 10398A were the two most independent prognostic factors. In vitro, the A549 ρ(0) cells showed more resistance to radiation than ρ(+) cells. Following radiation, ρ(0) cells showed delayed G2 arrest and lower ROS level as compared to ρ(+) cells. In conclusion, the present study suggests that in patients with NSCLC, low mtDNA content plus 10398A could be a marker of poor prognosis which is associated with resistance to anticancer treatment caused by low mtDNA content plus 10398A polymorphism resulting in mitochondrial dysfunction.
