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Saleh et al.                                                                                                                                                                   Improvement of prostate cancer detection

           risk of PCa development. However, in these studies,   METHODS
           PSA remains the best PCa predictor.  Another meta-
                                            [20]
           analysis research found a positive relation between   This study included 72 patients with PCa (mean age
           IGFBP-3 and PCa risk. However, the controversy     70.8 ± 5.3 years), 70 BPH patients (mean age 69.5 ±
           over the contradicted results of IGF-1 and IGFBP-3   7.3 years) and 56 healthy males (mean age 67.3 ± 7.2
           in these studies has been attributed to many factors   years) were randomly recruited among the volunteers
           such as race,  study design and assay features. [22]  of matched socioeconomic conditions and who did not
                       [21]
                                                              have any known significant disease. Full history and
           Chromogranin  A (CgA) is a member of the granin    clinical data were recorded for all subjects, and PCa
           family, of 439 kDa glycoprotein, and exists in the   patients  were  classified  into  localized  PCa  (n  =  54)
           secretory dense-core granules that contribute to the   and metastatic PCa (n = 18). BPH and healthy male
           storage of peptide hormones and catecholaminein    individuals (n = 126) were grouped as control. Patients
           all endocrine and neuroendocrine (NE) cells.  Thus,   with PCa underwent digital rectal examination, trans-
           it can be released from NE cells in a heterogeneous   rectal ultrasonography, guided biopsy of the prostate,
           circulating molecular form and is considered one of the   computed  tomography  scanning  of the pelvis, bone
           most abundant components of secretory granules.    scanning, and histopathological examination to assess
                                                         [23]
           While  its function is  unknown, through previous   metastatic disease and determine disease stage.
           decades a growing body of evidence has suggested
           that CgA is released in abnormal amounts by many   Blood samples
           malignant  NE  cells,  which  may  influence  different   A 10 mL blood sample was drawn in the morning after
           components of the tumor stroma and engage with the   overnight fasting from healthy subjects and one week
           regulation of tumor growth and progression. However,   following digital  rectal examination for  patients with
           increased blood CgA levels have been established as   prostatic diseases at the time of diagnosis.
           a useful indicator in the diagnosis of many NE tumors,   Serums of blood samples were separated and stored at
           but the use of this marker for clinical management is   -20 °C in a deep freeze until the date of analysis. Serum
           still controversial. [23,24]  Therefore, research has been   levels of IGF-1, IGFBP-3, CgA, total (tPSA) and free
           dedicated to its prognostic and diagnostic importance,   PSA (fPSA) were measured by chemiluminescence
           but with little supporting evidence for its use beyond   ELISA technique  IMMULITE,  DPC (Diagnostic
           common screening methods.  Several studies         Products Corporation, Los Angeles, CA, USA).
                                        [8]
           have reported that elevated CgA concentrations are
           associated with high-grade and advanced stage      Statistical analysis
           PCa. Some studies have indicated that increased    Serum concentrations of CgA, IGF-1, IGFBP-3, tPSA
           serum CgA exceeded PSA increase as a marker of     and fPSA in addition to combination among parameters
           progression to hormone-refractory disease. Therefore,   were expressed as arithmetic mean and standard
           it is possible to use CgA to monitor metastatic PCa   deviation.  Statistical  analysis was accomplished  by
           patients under androgen blockade.  Some indicate   using the  statistical package  IBM  SPSS  V20.  Data
                                           [25]
           CgA utility in early diagnosis, particularly when used in   between the groups were compared and the statistical
           combination with free/total PSA ratio,  however, some   significance  of  mean  values  was  determined  by
                                           [26]
           studies found that CgA does not precisely differentiate   applying independent sample t-test and Mann-Whitney
           malignant disease.  Similar debate occurs regarding   test. The significance level was established at the P
                            [27]
           CgA and tumor features  and CgA does not show      value of < 0.05. The validity (sensitivity and specificity),
                                  [28]
           any advantage in the prognosis of PCa  recurrence   accuracy  of each parameter and  ratios thereof were
           after radical prostatectomy or radiotherapy.       calculated  by area under  curve (AUC) in receiver
                                                         [29]
           Inconsistencies may be attributed to the transient and   operating characteristics (ROC) curve analysis.
           reversible process of neuroendocrine differentiation
           (NED) in most malignant prostate tumors; thus, these   RESULTS
           NE molecules are not constantly detectable. [5,30]
                                                              A total of 54 cases of localized PCa patients, mean age
           This  study  is  dedicated  to  evaluate  the  validity  of   70.3 ± 6.3 years, and 18 metastatic patients, mean age
           IGF-1, IGFBP-3, CgA and combination with PSA in    71.1 ± 5.5 years, were grouped as PCa patients with a
           diagnosis  of  patients  with  localized  and  metastatic   mean age of 70.8 ± 5.3 years (P > 0.05). Seventy BPH
           PCa.  The  secondary  objective  was  to  compare  the   patients, mean age 69.5 ± 7.3 years, and 56 healthy
           advantage of these markers in differentiation of PCa   male individuals, mean age 67.3 ± 7.2 years, were also
           patients.                                          included as a control group with a mean age of 68.3 ±
            84                                                                       Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ May 24, 2017
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