Serum levels of FAK and some of its effectors in adult AML: correlation with prognostic factors and survival

Focal adhesion kinase (FAK), human myofibrillogenesis regulator-1 (MR-1), ephrin receptor type A4 (EphA4), proto-oncogene tyrosine kinase Src (Src), and protein kinase C (PKC) are important markers in proliferation, survival, and migration in some cancers. However, the significance of each is still unclear in different malignancies, including acute myeloid leukemia (AML). Therefore, this study was conducted to investigate their serum levels in Egyptian adult de novo AML patients (n?=?70) against healthy volunteers (n?=?20). We managed to study the correlation between each pair and to investigate their association with diagnosis, prognosis, and survival. Serum levels were analyzed using enzyme-linked immunosorbent assay (ELISA). We found that FAK, MR-1, Src, and PKC serum levels were significantly higher in AML patients compared to control (p?<?0.0001), and this was associated with significantly lower EphA4 level (p?<?0.0001). Interestingly, we also observed a significant negative correlation of FAK (p?=?0.027), MR-1 (p?=?0.003), Src (p?=?0.038), and PKC (p?=?0.03) with patients’ overall survival (OS) while there was a positive significant correlation between EphA4 and OS (p?=?0.007). In conclusion, this study suggests that FAK, MR-1, EphA4, Src, and PKC may be used as early diagnostic and prognostic markers with high sensitivity and specificity in AML patients and thus may be incorporated into the patients’ early diagnostic and prognostic panels.

     

Growth hormone for risk stratification and effects of therapy in acute myocardial infarction

Abstract

Context: Excess growth hormone (GH) is associated with early mortality.

Objectives: We assessed the association of GH with prognosis after acute myocardial infarction (AMI), and the effects of secondary prevention therapies.

Methods: GH was measured using a high-sensitivity assay in 953 AMI patients (687 males, mean age 66.1?±?12.8 years).

Results: During 2 years follow-up, there were 281 major adverse cardiac events (MACE). Patients with MACE had higher GH levels (median [range], 0.91 [0.04–26.28] μg/L) compared to event-free survivors (0.59 [0.02–21.6], p?<?0.0005). In multivariate Cox survival analysis, GH was a significant predictor of MACE (hazard ratios 1.43, p?=?0.026 and 1.49, p?=?0.01, respectively) with significant interactions with beta blocker therapy (p?=?0.047) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACE/ARB) therapy (p?=?0.016).

Conclusions: GH levels post-AMI are prognostic for MACE and may indicate those patients who benefit from beta blocker and ACE/ARB therapy.     

Prognostic value of pre-treatment red blood cell distribution width in lung cancer: a meta-analysis

Abstract

Objective: In recent years, increasing studies found that pre-treatment red blood cell distribution width (RDW) could predict clinical outcomes in various cancers. However, the prognostic value of pre-treatment RDW in lung cancer was inconsistent. Therefore, we performed a meta-analysis to determine prognostic value of pre-treatment RDW in lung cancer.

Methods: We performed a search in PubMed, The Cochrane Library, EMBASE (via OVID), Web of Science, CNKI, Wanfang, VIP, SinoMed databases, then we identified all records up to February 15, 2019. Outcomes of interest were overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the relevance of pre-treatment RDW to OS in lung cancer.

Results: We included ten articles in total. Pooled results revealed that elevated pre-treatment RDW was significantly associated with poor OS (HR?=?1.55, 95% CI: 1.26–1.92, p?<?0.001) and DFS (HR?=?1.53, 95% Cl: 1.15–2.05; p?=?0.004) in lung cancer. Further subgroup analysis manifested that lung cancer patients with elevated pre-treatment RDW had worse prognosis.

Conclusions: A higher value of pre-treatment RDW indicated worse survival of patients with lung cancer. RDW may serve as a reliable and economical marker for prediction of lung cancer prognosis.     

Clinical implication of pretreatment neutrophil to lymphocyte ratio in soft tissue sarcoma

Introduction: Elevated neutrophil to lymphocyte ratio has been identified as a prognostic indicator in malignancies whereas; its association with extremity and trunk soft tissue sarcoma remain unclear. The aim of this study is to determine the utility of full blood neutrophil lymphocyte ratio (NLR) in preoperative diagnosis and its predictive value for survival in patients managed for soft tissue sarcoma of the trunk and extremities.

Method: 223 patients who presented with a soft tissue tumor were retrospectively reviewed. The study period was from January 2002–December 2009. Preoperative NLR as well as demographics, clinical and histopathological data were analysed.

Results: Full blood NLR was significantly higher in patient with a soft tissue sarcoma compared to benign soft tissue tumors (p < 0.001). Cox regression analysis demonstrated that elevated NLR >5 (p < 0.05) may be an adverse prognostic factor for Overall Survival.

Conclusion: The preoperative NLR is a simple, investigation predicting the preoperative diagnosis of a soft tissue sarcoma and a predictor of worse overall survival for patient with a soft tissue sarcoma.     

Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer

The objective of this study was to clarify whether the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are significant prognostic markers in patients with resectable colorectal cancer (CRC). A total of 200 patients who underwent curative resection for CRC were enrolled. The NLR and PLR were positively correlated (p?<?0.001). Both the NLR and PLR were shown to be good prognostic biomarkers of overall survival (OS) (p?=?0.002 and p?=?0.001, respectively). The PLR was an independent prognostic factor of OS based on multivariate analysis (hazard ratio, 1.971; 95% confidence interval, 1.102–3.335; p?=?0.021).     

Circulating biomarkers of hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy assessed by cardiac magnetic resonance

Abstract

Background: Myocardial fibrosis in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcomes. The availability of circulating biomarkers of myocardial fibrosis and hypertrophy would be helpful in clinical practice.

Objective: The aim of this study was to evaluate usefulness of various biomarkers of myocardial fibrosis and hypertrophy in HCM.

Methods: Levels of biomarkers: soluble ST2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 60 patients with HCM. All patients underwent cardiac magnetic resonance imaging to calculate parameters of hypertrophy and fibrosis.

Results: We observed positive correlations among sST2 levels and left ventricular mass (LVM) (r?=?0.32, p?=?0.012), LV mass indexed for the body surface area (LVMI) (r?=?0.27, p?=?0.036) and maximal wall thickness (MWT) (r?=?0.31, p?=?0.015). No correlation was found between Gal-3 and GDF-15 levels and hypertrophy and fibrosis parameters. We observed positive correlations among hs-cTnT levels and LVM (r?=?0.58, p?<?0.0001), LVMI (r?=?0.48, p?=?0.0001), MWT (r?=?0.31, p?=?0.015) and late gadolinium enhancement (LGE) mass (r?=?0.37, p?=?0.003). There were positive correlations between NT-proBNP levels and LVM (r?=?0.33, p?=?0.01), LVMI (r?=?0.41, p?=?0.001), MWT (r?=?0.42, p?<?0.001) and LGE mass (r?=?0.44, p?<?0.001).

Conclusions: Although no correlation between sST2 levels and myocardial fibrosis was found, sST2 may provide some additional information about hypertrophy extension. NT-proBNP and hs-cTnT are useful biomarkers in assessment of hypertrophy and fibrosis in HCM.     

Association between circulating irisin levels and epicardial fat in patients with treatment-naïve overt hyperthyroidism

Abstract

Background: Hyperthyroidism is associated with increased metabolic activity and thermogenesis. Irisin is a key molecule in thermogenesis and energy expenditure via adipose tissue browning. Epicardial fat was previously defined as brown-like fat. Thus, here we aimed to evaluate the association between serum irisin level and epicardial fat thickness (EFT) in patients with hyperthyroidism.

Methods: A total of 25 hyperthyroid patients and 24 age-, sex- and BMI-matched healthy controls were enrolled. Serum irisin levels, thyroid hormone levels, and body compositions were compared. EFT was measured via transthoracic echocardiography.

Results: Serum irisin level and EFT were significantly higher in the hyperthyroid group (p?<?0.001 and p?=?0.001, respectively). The distributions of fat-free mass, muscle mass and fat mass were similar between the study groups. Serum irisin level was negatively correlated with TSH (p?<?0.001) and positively correlated with fT3 (p?<?0.001), fT4 (p?<?0.001) and TSH receptor antibody (p?=?0.002) levels and EFT (p?=?0.001). In multivariate linear regression analysis, TSH (β?=??0.475, p?<?0.001) and EFT (β?=?0.290, p?=?0.023) levels were significantly associated with serum irisin levels.

Conclusions: An increased serum irisin level associated with EFT might contribute to metabolic derangement in hyperthyroidism. Further studies are needed to elucidate whether irisin levels and EFT are affected by hyperthyroidism or vice versa.     

Recurrence prediction using microRNA expression in hormone receptor positive breast cancer during tamoxifen treatment

Abstract

Purpose: To identify miRNAs associated with distant recurrence during tamoxifen treatment and build a recurrence prediction model.

Materials and methods: We measured the expression of five miRNAs (miR-134, miR-125b-5P, miRNA-30a, miR-10a-5p and miR-222). A total of 176 tumour tissues from 176 patients who had hormone receptor positive breast cancer with tamoxifen treatment were used to measure miRNA expression using quantitative real-time PCR (qRT-PCR).

Results: The five miRNAs were all up-regulated in distant recurrence cases within 5?years after surgery and during tamoxifen treatment. Kaplan-Meier survival analyses based on expression cut-offs determined by receiver characteristics curves (ROC) showed that high expression of miR-134, miR-125b-5P, miRNA-30a, miR-10a-5p and miR-222 were significantly (log-rank p-value =0.006, p-value <0.0001, p-value <0.0001, p-value <0.0001 and p-value <0.0001, respectively) associated with short relapse-free time. Our results were used to build a combined 3 miRNAs expression model. It could be used to categorize high-risk subset of patients with short relapse-free survival (AUC =0.891, p-value <0.0001).

Conclusions: Distant recurrence during tamoxifen treatment of hormone positive breast cancer might be affected by tamoxifen resistance related miRNAs. Such distant recurrence can be predicted using miRNA measurement.     

Long noncoding RNA Breast cancer antiestrogen resistance 4 is associated with cancer progression and its significant prognostic value

Breast cancer antiestrogen resistance 4 (BCAR4) is a novel long noncoding RNA. It was originally identified in a screen for genes responsible for the development of resistance to antiestrogens in breast cancer cells and plays a major role in various tumors. However, the clinical diagnostic role of BCAR4 in tumors is not completely understood. This current meta-analysis aimed to comprehensively explore the potential role of BCAR4 as a prognostic biomarker in a number of cancers. Five public databases PubMed, EMBASE, Web of Science, Wiley Online Library, and Medline were used to search for articles. Nine studies comprising 1,293 patients were included in this meta-analysis. The results of analysis showed that BCAR4 expression in human cancer was significantly associated with poor overall survival (hazard ratio [HR] = 1.98, confidence interval [CI]: [1.71–2.29]), p < 0.00001, and high BCAR4 expression was associated with clinical stage (OR and its 95% CI was 3.30 [1.99–5.46], p < 0.00001), distant metastasis (OR = 3.83, 95% CI: 2.15–6.82, p < 0.00001), and lymph node metastasis (OR and its 95% CI was 2.91 [1.62–5.25], p = 0.0004) in patients with cancer. Furthermore, the results revealed the prognostic significance of BCAR4 in gastrointestinal malignancy, breast cancer, and osteosarcoma (HR and its 95% CI were 2.05 [1.56–2.68], p < 0.00001; 1.78 [1.46–2.16], p < 0.00001; and 2.47 [1.41–4.34], p < 0.00001, respectively). This meta-analysis indicated the potential value of BCAR4 as a biomarker for predicting a poor prognosis in patients with cancer.     

Prognostic values of VEGF and IL-8 in malignant pleural effusion in patients with lung cancer

Abstract

Objective: The aim of this study was to evaluate the prognostic value of VEGF and IL-8 in pleural effusion in patients with lung cancer.

Materials and method: Commercially available ELISA was used to determine VEGF and IL-8 levels.

Results: The level of VEGF showed significant correlations with lymph node metastasis and distant metastasis. But, IL-8 was only correlated with lymph node metastasis. Univariate and multivariate analysis revealed elevated VEGF level was an independent predictor of shorter OS and DFS.

Conclusion: VEGF could be an important component that contributes to pleural effusion formation, and an important prognostic factor for lung cancer.     

The prognostic impact of tumour NSD2 expression in advanced prostate cancer

Abstract

Purpose: To assess the prognostic significance of the nuclear receptor binding SET protein 2 (NSD2), a co-activator of the NFkB-pathway, on tumour progression in patients with advanced prostate cancer (PCa).

Methods: We retrospectively assessed NSD2 expression in 53 patients with metastatic and castration-resistant PCa. Immunohistochemical staining for NSD2 was carried out on specimen obtained from palliative resection of the prostate. Univariable and multivariable analyses were performed to assess the association between NSD2 expression and PCa progression.

Results: Of the 53 patients, 41 had castration-resistant PCa and 48 men had metastases at time of tissue acquisition. NSD2 expression was increased in tumour specimen from 42 patients (79.2%). In univariable Cox regression analyses, NSD2 expression was associated with PSA progression, progression on imaging and overall survival (p?=?0.04, respectively). In multivariable analyses, NSD2 expression did not retain its association with these endpoints.

Conclusions: NSD2 expression is abnormal in almost 80% of patients with advanced PCa. Expression levels of this epigenetic regulator are easily detected by immunohistochemistry while this biomarker exhibited prognostic value for PCa progression and death in univariable analysis. Further studies on NSD2 involvement in PCa proliferation, progression, metastasis and resistance mechanisms are needed.     

Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer

Background: Elevated neutrophil to lymphocyte ratio (NLR) is linked with worse survival in many malignancies, whereas its association with pancreatic cancer (PC) remains unclear.

Methods: We retrospectively reviewed 95 patients with locally advanced or metastatic PC receiving gemcitabine-based chemotherapy. The prognostic value of NLR was evaluated.

Results: Elevated pretreatment NLR (>5) was observed in 16 out of 89 eligible patients, which was identified as an independent prognostic factor for overall survival (OS). The median OS for patients with elevated and normal NLR were 2.4 months and 7.7 months, respectively (p <0.001).

Conclusions: Elevated NLR is a predictor of shorter survival in patients with advanced PC.     

Serum interleukin-17 as a diagnostic and prognostic marker for non-small cell lung cancer

Abstract

Objective: The aim of this study was to explore the clinical role of serum interleukin (IL)-17 in patients with non-small-cell lung cancer (NSCLC).

Materials and method: Serum specimens from 128 patients with NSCLC and 60 healthy controls were collected. The concentrations of IL-17 were measured using enzyme-linked immunosorbent assay.

Results: Serum IL-17 levels were higher in the NSCLC group in comparison with the control group (p?<?0.01). With a cut-off value of 16?pg/ml, IL-17 showed a good diagnostic performance for NSCLC. Multivariate survival analysis indicated that IL-17 was an independent prognostic factor in NSCLC.

Conclusion: Measurement of IL-17 might be a useful diagnostic and prognostic value for patients with NSCLC.     

The correlation between pre-operative serum tumor markers and lymph node metastasis in gastric cancer patients undergoing curative treatment

Abstract

Background: There was few study concentrated on the correlation between the evaluated tumor markers and lymph node metastasis. In this study, we aimed to evaluate the correlation between the CA724, CA242, CA199, CEA and the lymph node metastasis of gastric cancer and assess the prognostic value of them in different N stage patients.

Methods: We analyzed the correlation between serum level of CA724, CA242, CA199, CEA and lymph node metastasis in 1501 gastric cancer patients.

Results: Lymph node metastasis of gastric cancer was related with tumor location, Bormann type, tumor size, histological type, depth of invasion and TNM stage (p?<?0.05). The values of CA724, CA242, CA199 and CEA were positively correlated with the metastatic lymph node counts and the N stage (p?<?0.05). The later the N stage was, the levels of CA724, CA242 and CA199 were higher. The later the N stage was, the positive rates of tumor markers were higher (p?<?0.05). In comparing with single tumor markers, the positive rates of tumor markers combination were higher. The combination of CA724?+?CA242?+?CA199?+?CEA had highest positive rate. The higher CEA level related to N1 stage patients while higher CA199 was related with poor prognosis for N1 stage patients. For N0 and N2 stage patients, evaluation of CA724 indicated poorer prognosis. For N1 and N2 stage gastric patients, the patients with increased CA242 inclined to have shorter survival time.

Conclusions: The tumor makers CA724, CA242, CA199 and CEA were evaluated significantly in the gastric patients with later N stage. The combination of these four tumor markers maybe prefer diagnostic index of gastric cancer and its lymph node metastasis. These tumor markers can be a possible indicator of poorer prognosis in different N stage patients.     

Characterization of soluble thrombomodulin levels in patients with stage 3–5 chronic kidney disease

Abstract

Objective: This study aims to test the serum levels of soluble thrombomodulin (TM) in patients with chronic kidney disease (CKD)3–5 and to assess their connection with the different stages and severity of disease.

Methods: Sixty-seven patients with CKD are included, disease severity was evaluated accordingly to CKD staging and clinical data is collected. Nineteen healthy volunteers served as healthy controls. Serum soluble TM is analyzed by ELISA.

Results: The levels of soluble TM in all patients with CKD were significantly higher than those of healthy controls (p?<?0.001). CKD5 patients showed higher serum levels of soluble TM, in comparison to CKD4 patients (p?=?0.001), CKD3 patients (p?<?0.001), and healthy controls (p?<?0.001). The correlation analysis revealed significant correlation between serum soluble TM and disease severity (r?=?0.714, p?<?0.001). Serum soluble TM was found to be correlated with eGFR (r?=??0.766; p?<?0.001) and serum creatinine (r?=?0.778, p?<?0.001).

Conclusion: Soluble TM concentrations significantly increase in the CKD patients and are associated with the severity of the disease. Soluble TM may play critical roles in the development of CKD, as a biomarker of endothelial cells damage, anticoagulation and anti-inflammation.     

Growth hormone and outcome in patients with intracerebral hemorrhage: a pilot study

Background: Endocrine alterations of the hypothalamic-pituitary-axis are one of the first measurable physiological changes in cerebral insults. During acute stress, human growth hormone (GH) is stimulated and has shown to have a prognostic value in various diseases. Within this pilot study, we evaluated the prognostic value of GH in patients with acute intracerebral hemorrhage (ICH).

Methods: In a prospective observational study in 40 consecutive patients with ICH, GH was measured on admission. The prognostic value of GH to predict 30-day mortality and 90-day functional outcome was assessed. Favorable functional outcome was defined as Barthel Index score >85 points and Modified Rankin Scale <3 points.

Results: GH levels were increased in patients who died within 30 days as compared to survivors (0.45 (IQR 0.20–1.51) vs. 1.51 (IQR 0.91–4.08) p?=?0.03), and in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome after 90 days 0.28 (IQR 0.16–0.61) vs. 0.78 (IQR 0.31–1.99) p?=?0.03). For mortality prediction, receiver-operating-characteristics revealed an area under the curve (AUC) on admission for GH of 0.78 (95% CI 0.60–0.96), which was in the range of the Glasgow Coma Score (GCS) (AUC 0.82 (95% CI 0.59–1.00) p?=?0.80). For functional outcome prediction, GH had an AUC of 0.71 (95% CI 0.54–0.87), which was statistically not different from the GCS (AUC 0.81 (95% CI 0.68–0.94) p?=?0.36).

Conclusions: In our small cohort of patients with acute ICH, elevated GH level were associated with increased mortality and worse outcome. If confirmed in a larger study, GH levels may be used as an additional prognostic factor in ICH patients. (ClincalTrials.gov number NCT00390962).     

A systematic review and meta-analysis of higher expression of folate receptor alpha (FOLR1) predicts poor cancer prognosis

Abstract

Folate receptor alpha (FOLR1), a glycosylphosphatidylinositol-linked protein, is a well characterized folate transporter. However, the prognostic power of FOLR1 in cancer remains controversial. We conducted a meta-analysis to assess the prognostic roles of FOLR1 on different cancers. Twelve studies involving 4471 patients were included in this meta-analysis. The pooled analysis indicated that high FOLR1 significantly predicted poor overall survival (OS) (pooled hazard ratio (HR)?=?0.78, 95% confidence interval (CI)?=?0.64–0.94, p?=?0.009) and the disease-free survival (DFS) (HR?=?1.25, 95% CI?=?1.07–1.47, p?=?0.005). Subgroup analyses based on tumour type found that high FOLR1 level was associated with poor OS in breast cancer (HR?=?2.66, 95% CI?=?1.54–4.59, p?=?0.0005) and endometrial carcinoma (HR?=?1.30, 95% CI?=?1.05–1.61, p?=?0.02). However, FOLR1 has relatively weakly correlation with gender, tumour size and chemotherapy. Additionally, overexpression of FOLR1 was correlated with grade, FIGO stage, vital status and nodule status. The present meta-analysis indicated that the high expression of FOLR1 is associated with the poor survival of cancer patients, which is helpful for the clinical decision-making process.     

Cell-free DNA as a prognostic marker in stage I non-small-cell lung cancer patients undergoing stereotactic body radiotherapy

Abstract

Objective: To evaluate whether plasma cell-free DNA (cfDNA) was related to clinical outcome in inoperable stage I non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiotherapy (SBRT).

Materials and methods: Plasma cfDNA was assessed at baseline, before the last day and 45 days after the end of SBRT, in 22 NSCLC patients. Twenty-two healthy controls were also evaluated.

Results: Plasma cfDNA was higher in patients than in controls. An association with unfavourable disease-free survival was found for continuous baseline cfDNA increments (HR?=?5.9, 95%CI: 1.7–19.8, p?=?0.04).

Conclusion: Plasma cfDNA may be a promising prognostic biomarker in high-risk NSCLC patients.