Comparison of HIF-1α and survivin levels in patients with diabetes and retinopathy of varying severity.

PURPOSE: This study measured serum hypoxia--inducible factor-1 (HIF-1α) and survivin levels in patients with diabetes and investigated their association with the severity of retinopathy. METHODS: This study included 88 patients with type 2 diabetes mellitus who underwent routine eye examinations. Three groups were created. Group 1 consisted of patients without diabetic retinopathy. Group 2 included patients with non-proliferative diabetic retinopathy. Group 3 included patients with proliferative diabetic retinopathy. To measure serum HIF-1α and survivin levels, venous blood samples were collected from patients. RESULTS: The mean HIF-1α levels in groups 1, 2, and 3 were 17.30 ± 2.19, 17.79 ± 2.34, and 14.19 ± 2.94 pg/ml, respectively. Significant differences were detected between groups 1 and 3 (p=0.01) and between groups 2 and 3 (p=0.01). The mean survivin levels in groups 1, 2, and 3 were 42.65 ± 5.37, 54.92 ± 5.55, and 37.46 ± 8.09 pg/ml, respectively. A significant difference was only detected between groups 2 and 3 (p=0.002). CONCLUSION: The present study revealed that serum HIF-1α and survivin levels are increased in patients with non-proliferative diabetic retinopathy compared to those in patients without diabetic retinopathy.

Clinical Significance of Circulating Tumor Cells (CTCs) and Survivin on Predicting Prognosis in Thyroid Cancer Patients.

BACKGROUND: Clinical significance of circulating tumor cell (CTC) count, mesenchymal CTCs (MCTCs), and survivin in patients with thyroid cancer remains unclear. We evaluated the relationship between the expression of different CTC subtypes or survivin and the prognosis in patients with thyroid cancer. Patients and Methods. This study enrolled 164 patients with thyroid cancer who were diagnosed from January 2013 to September 2020 in our hospital. Among these patients, there were 73 cases with papillary thyroid cancer (PTC), 60 cases with follicular thyroid cancer (FTC), 12 medullary thyroid cancers (MTC), 10 poorly differentiated thyroid cancers (PDTC), 9 anaplastic thyroid cancers, and 10 control patients with nonmalignant thyroid nodules based on their histopathological characteristics. Only 5 milliliters (mL) of peripheral blood from the patients with thyroid cancer and control was used to detect the CTC cell number via CanPatrol capture technique before treatments. We also isolated mononuclear cells (MNC) from the peripheral blood and performed quantity reverse transcriptase polymerase chain reaction (qPCR) for survivin gene expression among these patients. RESULTS: The overall positive rates of CTC at diagnosis were 56.1%. The relapse and metastasis rates in PTC and FTC patients with more than 6 CTCs and positive MCTCs were significantly higher than those in the patients with 6 or less than 6 CTCs and MCTCs. It was also found that these patients with >6 CTCs and MCTCs had shorter progression-free survival (PFS). Additionally, the survivin level of the patients with thyroid cancer was strongly relative to differentiation grades of thyroid cancers. CONCLUSIONS: The detection of more than six of total CTCs and positive MCTCs in the patients with differentiated thyroid cancer is an excellent biomarker for predicting the prognosis of patients. Survivin also is a good biomarker for thyroid cancer differentiation.

N-extended photoprotein obelin to competitively detect small protein tumor markers.

Two variants of Ca2+-regulated photoprotein obelin, extended from the N-terminus with small tumor markers - melanoma inhibitory activity protein (MIA) and survivin, one of the protein inhibitors of apoptosis, were designed, obtained and studied. Both domains in the obtained hybrid proteins exhibit the properties of the initial molecules: the main features of Ca2+-triggered bioluminescence are close to those of obelin, and the tumor markers' domains are recognized and bound by the corresponding antibodies. The obtained hybrids compete with the corresponding tumor markers for binding with antibodies, immobilized on the surface and their use has been shown to be promising as bioluminescent labels in a one-stage solid-phase competitive immunoassay.

Investigation of serum survivin in dogs suffering from cancer: a multicenter study.

BACKGROUND: In contrast to human medicine, only a small number of serum tumor markers are established in veterinary medicine even though they are a non-invasive diagnostic tool. OBJECTIVES: This study examined whether survivin could be suitable as a potential canine serum tumor marker. METHODS: This study measured the serum survivin concentrations of dogs with mammary tumors (n = 33), squamous cell carcinoma (n = 9), soft-tissue sarcoma (n = 18) and multicentric lymphoma (n = 22), using a commercially available, competitive immunoassay kit (BlueGene). The serum survivin concentrations were compared with those of a healthy control group (n = 20) and a control group of dogs with non-neoplastic diseases (n = 17). RESULTS: Dogs with malignant tumors had serum survivin concentrations between 15 and 5,906 pg/mL (median, 72 pg/mL), those in the healthy group ranged from 7 to 99 pg/mL (median, 21 pg/mL) and those in the group of dogs suffering from non-neoplastic diseases from 15 to 93 pg/mL (median, 42 pg/mL). The differences in the survivin concentrations between the healthy dogs and dogs with malignant tumors and between the dogs with non-neoplastic diseases and those with malignant tumors were significant (p < 0.001 and p = 0.006, respectively). CONCLUSIONS: The serum survivin concentrations in dogs with malignant tumors, with some exceptions, are higher than in dogs with benign tumors and dogs that do not suffer from a malignancy. Therefore, survivin can provide information on the presence of malignant tumors and be used as a tumor marker in dogs.

Circulating Survivin Protein Levels in Lung Cancer Patients Treated With Platinum-Based Chemotherapy.

The survivin protein contributes to the development and progression of tumors. Protein expression and mRNA levels correlate with clinicopathological parameters and survival of cancer patients. Our purpose was to evaluate whether circulating survivin levels have any diagnostic or predictive value in lung cancer. 118 patients with advanced stage lung cancer participated in our study. 53 suffered from adenocarcinoma (ADC), 33 from squamous cell carcinoma (SqCC), and 32 from small cell lung cancer (SCLC). We also enrolled 21 control subjects. Blood samples were collected before and after two cycles of chemotherapy. We measured survivin concentrations with ELISA. Non-parametric tests were used for analysis. We did not find significant difference in survivin levels between patients and control subjects (17.19/0-829.74/vs. 49.13/0-165.92/pg/ml; p = 0.07). We found lower survivin concentrations in patients with SqCC (0/0-171.24/pg/ml) than in those with ADC (24.94/0-626.46 pg/ml) and SCLC (45.51/0-829.74/pg/ml) (ADC vs. SqCC p < 0.0001, ADC vs. SCLC p = 0.0405, SqCC vs. SCLC p < 0.0001). Survivin levels were higher in stage IV patients than in patients without distant metastases (p = 0.0061), and concentrations were progressively higher with increasing number of metastatic organ sites (p = 0.04). We observed a decrease in survivin levels in ADC patients after platinum plus pemetrexed chemotherapy (26.22/0-626.46/pg/ml before vs. 0/0-114.36/pg/ml after; p = 0.01). Neither progression-free nor overall survival correlated with survivin levels at baseline. Our data imply that survivin may be involved in the development of metastases and it might be used as a biomarker of disease progression. However, circulating survivin concentrations do not predict survival of patients with lung cancer.

Serum survivin is decreased in women with preeclampsia.

Objective: To evaluate the serum survivin level in preeclampsia.Methods: Eighty-eight pregnancies complicated with preeclampsia and 88 gestational-age (GA)-matched uncomplicated pregnancies were evaluated.Results: Mean serum survivin was detected to be significantly decreased in the early- (EOPE) and late-onset (LOPE) preeclampsia subgroups than the GA-matched control-groups; and were comparable in EOPE- and LOPE-groups after correction for GA. Serum survivin had weak negative correlations with systolic and diastolic arterial blood pressure.Conclusion: The serum survivin level was decreased in preeclamptic patients than the GA-matched controls. More comprehensive studies are needed to clarify the timing and extent of placental apoptosis in preeclampsia.

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.

Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.

Analysis of Curcumin as a Radiosensitizer in Cancer Therapy with Serum Survivin Examination: Randomised Control Trial.

OBJECTIVE: One of the important treatments for cervical cancer is radiation therapy. This study sought to determine the role of curcumin as a radio-sensitizing agent for use with radiation therapy for cervical cancer. To accomplish this, we assessed the levels of survivin, which is an anti-apoptotic protein that plays a role in cell division and apoptosis inhibition. METHOD: This study used a quasi-experimental design, including a pretest-posttest control group design approach. The study subjects included cervical carcinoma stage IIB-IIIB patients who were scheduled to undergo surgery at the Hasan Sadikin Hospital Bandung during the research period. The advanced cervical cancer patients were assigned to two groups: i) those who received curcumin + radiation therapy and ii) those who received placebo + radiation therapy. RESULTS: In the group treated with curcumin + radiation, 15 (75%) patients showed decreased survivin levels and 5 (25%) showed increased survivin levels. Whereas, in the placebo + radiation group, there were 8 (40%) patients who showed decreased survivin levels and 12 (60%) who showed increased survivin levels. CONCLUSION: In conclusion, curcumin is an effective, alternative radiosensitizer agent for application in cervical cancer treatment.
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Downregulation of serum survivin correlates with increased inflammation, enhanced disease severity and worse prognosis in sepsis patients.

This study aimed to determine the role of survivin in sepsis patients.Serum samples of 288 sepsis patients and 290 healthy individuals (as healthy controls) were collected 24 hours within enrollment. Serum survivin and inflammatory cytokines were detected by enzyme-linked immunosorbent assay, and biochemical indexes were recorded. In sepsis patients, acute pathologic and chronic health evaluation II score and sequential organ failure assessment score were evaluated, and 28-day mortality was recorded.Survivin was greatly decreased in sepsis patients compared to healthy controls (P < .001) and it predicted decreased sepsis risk (area under curve (AUC): 0.921, 95% confidence interval (CI): 0.900-0.942). For clinical characteristics of sepsis patients, survivin was negatively correlated with acute pathologic and chronic health evaluation II score (P < .001), score and sequential organ failure assessment score (P < .001), serum creatinine (P < .001), white blood cell (P = .037), C-reactive protein (P < .001), tumor necrosis factor-α (P < .001), interleukin (IL)-1ß (P < .001), IL-6 (P < .001), and IL-8 (P < .001), while positively correlated with albumin (P < .001). For prognosis of sepsis patients, survivin was decreased in deaths compared to survivors (P < .001), and it predicted decreased death risk (AUC: 0.625, 95% CI: 0.558-0.692). Meanwhile, accumulating mortality was decreased in survivin high patients compared to survivin low patients (P = .006). However, multivariate logistic regression revealed survivin was not an independent predictive factor for 28-day mortality, indicating it might interact with other independent factors to affect prognosis of sepsis patients.Survivin was decreased in sepsis patients and predicted decreased sepsis risk. Meanwhile, survivin was correlated with declined inflammation, reduced disease severity, and favorable prognosis in sepsis patients.

Diagnostic Role of Survivin in Rheumatoid Arthritis: A Systematic Review.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which is characterized by the hyperplasia of synovial tissue. Survivin is a member of the inhibitor of apoptosis protein family, which facilitates the formation of functional T-cell receptor and differentiation of memory T cells. Survivin plays an important role in the expression of major histocompatibility complex molecules and mature dendritic cells, which play the main role in the etiology of RA. This systematic review was conducted to investigate the evidence on the role of survivin as a diagnostic and predictive value in RA patients. All published articles related to the subject of interest and published up to 30 March 2018 were searched in three databases, including Google Scholar, PubMed, and Web of Science. After a detailed evaluation of the full-text version of the papers, 23 articles were entered into the study. The elevation of survivin in the preclinical phase of RA and its association with anti-cyclic citrullinated peptide (CCP) antibodies suggested it as a predictor of RA. Recently, survivin has been introduced as the biomarker of joint damage and poor response to antirheumatic treatment in RA patients. Based on the evidence, survivin level had high specificity and sensitivity in the diagnosis of RA patients. The results of the reviewed studies demonstrated that a positive survivin level was associated with the presence of anti-CCP antibodies.

Clinical Features and Expression Patterns for Burn Patients Developed Marjolin Ulcer.

Marjolin's ulcer is a type of skin cancer that generated from chronic nonhealing trauma. For years, its pathogenesis mechanisms remain unclear. Regarding this situation, the authors retrospectively analyze the patients admitted to their department from 2005 to 2019 to present several representative cases and examine the expression patterns of survivin and its role in this process. Among these patients, the latent period ranges from 2 to 25 years, with 8.43 years in average. There is no notable relationship between the latent period and age (P = .643 > .05). Therefore, Marjolijn's ulcer arises from extremities and joints more often compared with other parts (P < .05). The expression ratio of survivin in Marjolin's ulcer is significantly higher than that in skin ulcer (P < 0.05). And the expression ratio of survivin in patients diagnosed with Marjolin's ulcer is also correlated with lymphatic metastasis (P < .05). Frequent follow-ups and prompt diagnosis and management are necessary as the prognosis is poor for patients with metastasis. Survivin may be a potential target for future development of target therapy in order to maximize the efficacy and improve the quality of life for patients suffering from Marjolin's ulcer.

microRNA involvement in the regulation of survivin in peripheral blood mononuclear cells from rheumatoid arthritis patients.

AIM: Impaired regulation of immune tolerance results in autoimmune diseases, such as rheumatoid arthritis (RA). Survivin is an anti-apoptotic protein and can induce cellular mitosis. In the current study, we assessed the transcript level of total survivin (survivin-TS) and its three major variants and evaluated the expression level of important micro RNAs (miRNAs) involved in survivin expression regulation in RA patients. METHOD: Peripheral blood mononuclear cells (PBMCs) were isolated from 50 healthy controls and 50 RA-active patients. RNA extraction was performed and then single-strand complementary DNA was synthesized. Quantitative real-time polymerase chain reaction was used to assess the expression level of survivin-TS and its variants with effective miRNAs in PBMCs. RESULTS: Overexpression of survivin-2B (fold change = 1.57, P = 0.005), survivn-ΔEx3 (fold change = 1.93, P = 0.009) and downregulation of survivin-WT (fold change = 0.64, P = 0.0002) were found in PBMCs of patients, while messenger RNA (mRNA) expression of survivin-TS had no significant difference between RA patients and controls. Expression levels of miR-335-5p, miR-485-5p, miR-16-5p, miR-150-5p, miR-34a-5p, and miR-203a-3p were significantly increased in PBMCs from patients compared with healthy controls. In a correlation study, dysregulation of these miRNAs were not correlated with mRNA expression level of survivin. CONCLUSION: While survivin-TS was not differently expressed in RA patients, its variants had altered expression. Although miRNAs were aberrantly expressed in PBMCs from RA subjects, they did not regulate survivin-TS. miRNAs might be involved in RA pathogenesis, but not through controlling survivin.

Significance of Serum Survivin and -31G/C Gene Polymorphism in the Early Diagnosis of Breast Cancer in Egypt.

BACKGROUND: Breast cancer is one of the most relevant malignancies among women. Molecular abnormalities in promotor region of survivin gene may account for overexpression of survivin and increased breast cancer risk. This study aimed to explore the potential association between survivin promotor gene -31G/C single nucleotide polymorphism (rs9904341) and its serum level alteration on one hand, and the risk of breast cancer in Egyptian patients on the other hand. It also aimed to assess the usefulness of survivin as an early noninvasive diagnostic biomarker and in breast cancer staging. PATIENTS AND METHODS: A total of 135 patients with physically and pathologically confirmed breast cancer and 40 unrelated control subjects as well as 40 patients with benign breast mass were recruited from the early detection unit at National Cancer Institute, Cairo University. Genotyping was performed using allelic discrimination probes by real-time quantitative PCR and serum survivin by enzyme-linked immunosorbent assay. RESULTS: The minor allele C of -31G/C survivin single nucleotide polymorphism was more frequent in breast cancer patients (19.3%) compared to the control group (7.5%). Furthermore, subjects with the GC + CC genotype were at increased risk of breast cancer compared to the GG genotype of the control group and also the benign group. Moreover, those patients exhibited higher serum levels of survivin compared to GG genotype. There was also significant elevation of serum survivin in different breast cancer stages. CONCLUSION: Genetic variation in -31G/C of the survivin gene may contribute to the disposition of breast cancer in the Egyptian population. Serum survivin alteration played a pivotal role in the pathogenesis of breast cancer.

Cardiac biomarkers improve prediction performance of the combination of American Society of Anesthesiologists physical status classification and Americal College of Surgeons National Surgical Quality Improvement Program calculator for postoperative mortality in elderly patients: a pilot study.

BACKGROUND: Our previous research has shown American Society of Anaesthesiologists physical status classification (ASA) score and Americal College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator to have the most accuracy in the prediction of postoperative mortality. AIMS: The aim of our research was to define the most reliable combination of cardiac biomarkers with ASA and ACS NSQIP. METHODS: We have included a total of 78 patients. ASA score has been determined in standard fashion, while we used the available interactive calculator for the ACS NSQIP score. Biomarkers BIRC5, H-FABP, and hsCRP have been measured in specialized laboratories. RESULTS: All of the deceased patients had survivin (BIRC5) > 4.00 pg/ml, higher values of H-FABP and hsCRP and higher estimated levels of ASA and ACS NSQIP (P = 0.0001). ASA and ACS NSQIP alone had AUC of, respectively, 0.669 and 0.813. The combination of ASA and ACS NSQIP had AUC = 0.841. Combination of hsCRP with the two risk scores had AUC = 0.926 (95% CI 0.853-1.000, P < 0.0001). If we add three cardiac biomarkers to this model, we get AUC as high as 0.941 (95% CI 0.876-1.000, P < 0.0001). The correction of statistical models with comorbidities (CIRS-G score) did not change the accuracy of prediction models that we have provided. DISCUSSION: Addition of ACS NSQIP and biomarkers adds to the accuracy of ASA score, which has already been proved by other authors. CONCLUSION: Cardiac biomarker hsCRP can be used as the most reliable cardiac biomarker; however, the "multimarker approach" adds the most to the accuracy of the combination of clinical risk scores.

Clinical significance of plasma anti-TOPO48 autoantibody and blood survivin-expressing circulating cancer cells in patients with early stage endometrial carcinoma.

PURPOSE: To examine the clinical significance of an autoantibody (AAb) against a novel tumor-associated antigen (TAA) derived from human DNA-topoisomerase I, termed as TOPO48 AAb, and peripheral blood survivin-expressing circulating cells (CCC) in patients with early stage endometrial cancer (EC). METHODS: Blood samples were collected from 80 patients with early stage EC and 80 age-matched healthy subjects. Plasma levels of the TOPO48 AAb were measured with a specific antibody capture enzyme-linked immunosorbent assay (ELISA) and blood survivin-expressing CCC assessed with a reverse transcription-polymerase chain reaction products based on a hybridization-enzyme-linked immunosorbent assay (RT-PCR-ELISA). Sixty patients were followed up for 36 months after the initial assay test. RESULTS: There were 75% and 60% samples with positive levels of the TOPO48 AAb and survivin-expressing CCC in the cancer patients, respectively. However, the cumulative positive rate of combination of the two markers was increased to 93.3% with 0.927 (95% CI 0.871-0.984) of area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. During the follow-up period, patients with positive TOPO48 AAb but negative surviving-expressing CCC had a higher survival rate and a longer survival time than those with negative AAb but positive CCC (P = 0.01). CONCLUSIONS: The combination of TOPO48 AAb and survivin-expressing CCC may be used as a novel recipe to improve the efficiency of early diagnosis and provide more accurate prognostic prediction in patients with early stage EC.

The -31 G/C promoter gene polymorphism of surviving in Turkish colorectal cancers patients

Introduction: Survivin (also known as birc5) is the first protein discovered among the apoptosis-regulating gene family referred to as inhibitor of apoptosis proteins (IAPs). It is expressed and controlled during cellular differentiation and development in human beings. Survivin expression has been shown in a number of cancers and has been associated with cancer development. Objective: In our study, we compared with blood samples as our control and normal- tumoural tissue samples, which obtained from the same tissue of 100 cases diagnosed with colorectal cancer, at Department of Pathology, Istanbul University. Methods: The present study employed PCR-RFLP to identify the -31 G/C polymorphism in the promoter region of the survivin gene. Distribution of the survivin polymorphism was compared between control and tumoural tissue samples using the chi-square test. Results: Comparison of all samples revealed that there was significant difference in distribution of survivin promoter -31G/C between control group and tumour and normal tissue of the patient group (p<0.05). When genotypes of the control and tumour tissues were compared according to gender, there was no statistically significant difference in the distribution of survivin promoter -31G/C in females p=0.420 or males p=0.309. Conclusion: A significant difference was seen in distribution of C allele in tumour tissue compared to normal tissue.

Circulating Survivin Levels in Obstructive Sleep Apnoea.

INTRODUCTION: Obstructive sleep apnoea (OSA) is characterised by a low-grade systemic and airway inflammation; however, the regulatory mechanisms of inflammation are poorly explored. Survivin (Birc5) is an anti-apoptotic protein which inhibits Type 1 inflammation; however, this molecule has not been investigated in OSA. METHODS: Forty-five patients with OSA and 31 non-OSA control subjects were involved. Venous blood was collected for plasma survivin measurements before and after diagnostic overnight polysomnography. Plasma survivin levels were compared between the two groups and correlated to OSA severity and comorbidities. RESULTS: Plasma survivin levels were lower in OSA in the evening (27.6 ± 89.9 vs. 108.3 ± 161.2 pg/ml, p < 0.01) and in the morning (17.4 ± 48.6 vs. 36.4 ± 69.2 pg/ml, p = 0.02) compared to the control group. This OSA-related decrease was also present when only the non-obese patients were analysed. Significant indirect relationships were observed between plasma survivin levels and measures of OSA severity such as the apnoea-hypopnoea index (r = - 0.45) or oxygen desaturation index (r = - 0.40, both p < 0.01); however, when adjusting to BMI, these became insignificant (p > 0.05). Low plasma survivin concentrations were associated with high BMI (r = - 0.35), high CRP (r = - 0.31), low HDL cholesterol (r = 0.24) and high triglyceride levels (r = - 0.24, all p < 0.05). CONCLUSION: Plasma survivin levels are reduced in OSA, relate to disease severity, and are associated with high CRP levels. This suggests an impaired immunoregulation in this disorder which needs to be studied in further detail.

Significance of survivin mRNA blood levels in patients with melanoma.

PURPOSE: Survivin represents a key anti-apoptotic molecule that is highly expressed in the vast majority of tumors. The aim of the study was to examine the significance of survivin mRNA blood levels in melanoma patients. METHODS: In this prospective translational research study, survivin mRNA blood levels were measured in melanoma patients treated with adjuvant interferon or systemic treatment for advanced disease. RESULTS: Sixty-four patients with melanoma and 40 healthy controls were included. The majority of them had tumor stages III and IV. The upper 95% confidence interval (95%CI) of survivin levels in controls was set as normal cut-off. Fifty-two (81.3%) patients had survivin levels above normal cut-off. Melanoma patients had higher survivin levels than controls (p<0.0001). Survivin levels were non-significantly higher in stage III compared to stage IV patients. Patients with survivin levels above vs. below median had median progression-free survival (PFS) 19.5 months vs. 7.4 months (p=0.045), but median overall survival (OS) not reached vs. 18.4 months (p=0.091). Cox proportional hazard models showed that only tumor stage was associated with PFS and OS. There was no statistically significant change in survivin levels between baseline and during treatment (p=0.845) or during follow-up (p=0.101). CONCLUSION: Although melanoma patients had significantly higher survivin levels than controls, the study showed that survivin mRNA blood levels did not represent an independent prognostic factor for patients with melanoma. The role of circulating survivin should be further examined in larger studies.