METHODS: RNA was isolated from peripheral whole blood samples (2 x 10 ml) collected from NPC patients/controls (EDTA vacutainer). Gene expression patterns from 99 samples (66 NPC; 33 controls) were assessed using the Affymetrix array. We also collected expression data from 447 patients with other cancers (201 patients) and non-cancer conditions (246 patients). Multivariate logistic regression analysis was used to obtain biomarker signatures differentiating NPC samples from controls and other diseases. Differences were also analysed within a subset (n=28) of a pre-intervention case cohort of patients whom we followed post-treatment.
RESULTS: A blood-based gene expression signature composed of three genes - LDLRAP1, PHF20, and LUC7L3 - is able to differentiate NPC from various other diseases and from unaffected controls with significant accuracy (area under the receiver operating characteristic curve of over 0.90). By subdividing our NPC cohort according to the degree of patient response to treatment we have been able to identify a blood gene signature that may be able to guide the selection of treatment.
CONCLUSION: We have identified a blood-based gene signature that accurately distinguished NPC patients from controls and from patients with other diseases. The genes in the signature, LDLRAP1, PHF20, and LUC7L3, are known to be involved in carcinoma of the head and neck, tumour-associated antigens, and/or cellular signalling. We have also identified blood-based biomarkers that are (potentially) able to predict those patients who are more likely to respond to treatment for NPC. These findings have significant clinical implications for optimizing NPC therapy.
MAIN BODY: In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME.
CONCLUSIONS: It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.
MATERIALS AND METHODS: We analyzed Ki 67 immuno-histochemistry of 31 consecutive cases staged III giant cell tumor to determine the clinico-pathological correlation. There were 19 male patients compare to 12 females. The mean age was 33.8 years ranged from 18 to 59 years. Five cases presented with local recurrence prior to wide resection and one case had multiple recurrences there after. Six cases had pulmonary metastases. Expression of Ki 67 antigen was evaluated by immuno-histochemical staining techniques using the avidin-biotin perioxidase complex method using an LSAB2 kit (Dako, Glostrup, Denmark). The primary antibody used in this study was Ki-67 (MIB-I clone, dilution 1:25; Dako).
RESULTS: The mean value of Ki-67 index obtained as a percentage of 1000 background cells was 8.15 (ranged 1.00 - 20.0). The median Ki 67 index was 7.5 with standard deviation of 5.12. The Ki 67 index of recurrence tumor was 4.323 compared to 6.05 without recurrence and was not statistically significant (mean difference of 0.865 with p value in independent t test of 0.736). The Ki 67 index was also not statistically significant in the presence of pulmonary metastases with the mean value of metastases group of 6.681 compared to 2.890 without metastases (mean difference of 1.895 with p value in independent t test of 0.424).
CONCLUSION: Ki 67 index is not use-full prognostic marker for aggressive type of giant cell tumor of the bone.