CCR6 Is a Predicting Biomarker of Radiosensitivity and Potential Target of Radiosensitization in Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). MATERIALS AND METHODS: RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based γH2AX quantification. RESULTS: The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency. CONCLUSION: CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.

Increased pretreatment levels of serum LDH and ALP as poor prognostic factors for nasopharyngeal carcinoma / 癌症

Serum enzymes that play potential roles in tumor growth have recently been reported to have prognostic relevance in a diverse array of tumors. However, prognosis-related serum enzymes are rarely reported for nasopharyngeal carcinoma(NPC). To clarify whether the level of serum enzymes is linked to the prognosis of NPC, we reviewed the pretreatment data of lactate dehydrogenase(LDH), alkaline phosphatase (ALP), and glutamyl transferase (GGT) in 533 newly diagnosed NPC patients who underwent radical radiotherapy between May 2002 and October 2003 at Sun Yat-sen University Cancer Center. Patients were grouped according to the upper limit of normal values of LDH, ALP, and GGT. The Kaplan-Meier method and log-rank test were used for selecting prognostic factors from clinical characteristics and serum enzymes, and the chi-square test was applied to analyze the relationships of clinical characteristics and serum enzymes. Finally, a Cox proportional hazards model was used to identify the independent prognostic factors. We found that increased levels of LDH had poor effects on both overall survival and distant metastasis-free survival (P = 0.009 and 0.035, respectively), and increased pretreatment level of serum ALP had poor effects on both overall survival and local recurrence-free survival (P = 0.037 and 0.039, respectively). In multivariate analysis, increased LDH level was identified as an independent prognostic factor for overall survival. Therefore, we conclude that increased pretreatment serum LDH and ALP levels are poor prognostic factors for NPC.

Establishment of a specific serum proteomic profile model of nasopharyngeal carcinoma by MALDI-TOF MS / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the specific serum peptide profile by comparing the serum differences between nasopharyngeal carcinoma patients (NPC) and normal control subjects, and to provide a diagnostic model of nasopharyngeal carcinoma.</p><p><b>METHODS</b>Pre-treatment serum samples of NPC and normal control subjects were collected and assayed by MALDI-TOF MS analysis. The peptides were extracted with magnetic beads coated with WCX. Mass spectrographic data were analyzed with ClinProt(TM) software. The specific serum peptide model of NPC was established by using genetic algorithms. The sensitivity and specificity of model were tested by blind testing.</p><p><b>RESULTS</b>The serum peptidome patterns of nasopharyngeal carcinoma was obtained. Differential expression of 99 peptide peaks was deteced, and the 808.99 Da, 834.61 Da, 3954.82 Da, 8141.88 Da peptide peaks showing statistically significant differences between the two groups, were used to establish the diagnostic model for nasopharyngeal cancer. The recognition rate and predictive power of the model were 90.0% and 84.3%, respectively. The sensitivity and specificity of the model were 80.0% and 64.0% determined by blind testing, respectively.</p><p><b>CONCLUSIONS</b>Significant differences of serum peptide peaks are detected between NPC and normal control groups. The established specific serum peptide model may have certain application in the diagnosis of nasopharyngeal carcinoma, and provides the basis for discovering specific tumor markers of nasopharyngeal carcinoma.</p>

Continuous fall in hemoglobin level is a poor prognostic factor in patients with nasopharyngeal carcinoma treated with radiotherapy / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Anemia can not only reduce the quality of life of patients with cancer, but also affect their survival. This study was to investigate the prognostic value of hemoglobin (Hb) level in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy.</p><p><b>METHODS</b>Clinical data of 520 NPC patients received definitive radiotherapy between 2000 and 2002 at Sun Yat sen University Cancer Center were analyzed. Patients were stratified into normal Hb level and anemia groups according to their Hb levels before, during, and after radiation. Anemia was defined according to World Health Organization criteria as Hb level < 130 g/L in men and < 120 g/L in women. Hb continuous decrease group and non decrease group were defined according to Hb changes in the patients during radiotherapy. Loco regional recurrence free survival (LRFS) and overall survival (OS) rates were estimated using the Kaplan Meier method. Multivariate analysis was performed using the Cox model to analyze the prognostic factors.</p><p><b>RESULTS</b>Before radiation, the 5 year LRFS rates were 60.9% in anemia group and 63.9% in normal Hb level group (P = 0.337); the 5 year OS rates were 65.2% and 71.0%, respectively (P = 0.299). During radiation, the 5 year LRFS rates were 56.7% in anemia group and 67.9% in normal Hb level group (P = 0.013); the 5 year OS rates were 61.0% and 75.9%, respectively (P = 0.001). After radiation, the 5 year LRFS rates were 59.6% in anemia group and 64.9% in normal Hb level group (P = 0.169); the 5 year OS rates were 65.0% and 71.9%, respectively (P = 0.090). The 5 year LRFS and OS rates were significantly lower in Hb continuous decrease group than in Hb non decrease group (59.1% vs. 69.3%, P = 0.032; 66.2% vs. 76.4%, P=0.011). Multivariate analysis showed that the continuous decrease of Hb was an independent prognostic factor for OS.</p><p><b>CONCLUSION</b>The change in Hb level during radiotherapy is an important prognostic factor affecting the OS of NPC patients.</p>