Author Correction: The Expression Analysis of Intestinal Cancer Stem Cell Marker Lgr5 in Colorectal Cancer Patients and the Correlation with Histopathological Markers (Journal of Gastrointestinal Cancer, (2020), 51, 2, (591-599), 10.1007/s12029-019-00295-w)

The original version of this article unfortunately contained a mistake. In the author group section, the correct name of the first author is �Shirin Salehzadeh.� The authors apologize for this oversight and for any confusion it may have caused. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

A new insight into cancer stem cell markers: Could local and circulating cancer stem cell markers correlate in colorectal cancer?

Cancer stem cell (CSC) markers could serve as potential prognostic procedure. This study is aimed to investigate the local expression of doublecortin-like kinase 1 (DCLK1) and Lgr5 in colorectal cancer tissues (CRC) at both protein and messenger RNA (mRNA) level, followed by providing a comparison of the local and circulating expression pattern of these markers, based on our present and previous study. The mRNA expression level of DCLK1 and Lgr5 was evaluated using comparative real-time PCR method applying 58 fresh tumor tissues and their correspondent normal margins. Immunohistochemistry was applied to analyze the protein expression level of DCLK1 and Lgr5 in paraffin-embedded CRC tissues. The correlation of DCLK1 and Lgr5 expression pattern with clinicopathological characteristics was assessed. A higher mRNA expression level of DCLK1 (3.28-fold change, p < 0.001) and Lgr5 (2.29-fold change, p < 0.001) was observed in CRC fresh tissues compared to the normal adjacent margins, and the expression level was higher in patients with higher grade and stages of disease and patients who underwent neoadjuvant chemoradiotherapy (CRT). The protein expression level of DCLK1 and Lgr5 was also increased significantly in tumor tissues compared to normal colon tissues which were positively correlated to tumor stage and grade and neoadjuvant CRT. Taken together, the results of protein analysis were in accordance with mRNA assessment. The local expression pattern of DCLK1 and Lgr5 was also in accordance with their expression level in circulation. However, some minor inconsistencies were observed which may be attributed to several factors including the possible effect of CRT on CSC reprogramming. © 2015, International Society of Oncology and BioMarkers (ISOBM)

The Expression Analysis of Intestinal Cancer Stem Cell Marker Lgr5 in Colorectal Cancer Patients and the Correlation with Histopathological Markers

Introduction: Cancer stem cells (CSCs) have frequently been utilized in the cell characterization and identified responsible for tumor development, metastasis, recurrence, and chemoresistance. CSC surface markers function in cancer cell signaling and are indicated as potential biomarkers for cancer diagnosis and prognosis. As well, dysregulation of cancer-related signaling pathways could promote CSC development and progression. Our aim was to evaluate the expression of colorectal CSC markers and their correlation with cancer proliferation and angiogenesis. Methods: In this case-control study, total RNA was extracted from a total of 74 colorectal tumors and 74 adjacent normal tissue biopsies. Then, using a quantitative real-time PCR, the relative expression levels of Lgr5 and Lrig1 were measured in all malignant and healthy samples. Also, immunohistochemical (IHC) staining of tumor tissues was performed for Ki-67 (proliferation) and CD34 (angiogenesis) markers, and the immunoexpression staining scores were obtained. The diagnostic value of the genes was evaluated using receiver operating characteristic (ROC) curve. Possible correlation between CSC markers and immunohistochemical markers in CRC was analyzed by Pearson�s correlation test and linear regression. Results: The expression level of Lgr5 in tumor samples showed a significant increase compared with normal samples (p &lt; 0.001) with a fold change of 2.54 (± 0.182). However, there was no significant difference in the relative expression of Lrig1 gene in tissue samples of healthy subjects and patients. The analysis of the ROC showed an AUC of 0.92 for Lgr5 and sensitivity 80 and specificity 96. Further analysis revealed a significant correlation between mRNA levels of Lgr5 and immunoexpression of Ki-67 (r2 = 0.680, p &lt; 0.001). Conclusion: The high expression levels of Lgr5 found in tumor tissues were correlated with histological parameters, indicating a significant role in CRC development and diagnosis. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

The added value of trabecular bone score in fracture risk assessment of kidney transplant recipients

Introduction. Trabecular Bone Score (TBS) is an index of bone microarchitecture independent of Bone Mineral Density (BMD). Recently, TBS data has been used to optimize the predictive value of the Fracture Risk Assessment Tool (FRAX). The aim of this study was to evaluate the clinical value of FRAX adjustment with TBS in kidney transplant recipients. Methods. Seventy post-transplant Iranian kidney recipients were included in this study. After the evaluation of BMD and TBS, the risk of major osteoporotic fracture (MOF) and hip fracture (HF) was assessed once with and once without TBS adjustment. The proportion of patients who needed a therapeutic intervention was compared before and after TBS adjustment. The association between TBS and BMD data was also evaluated. Results. The mean age of the patients was 54 ± 8.8 years (range: 40 to 77). The mean TBS of the patients was 1.30 ± 0.12. In multivariate analysis, the TBS was significantly associated with the age (P < .05) and dialysis period (P < .05). A strong correlation was found between the spine BMD and TBS data (r = 0.612, P < .001). A significant correlation was found between the MOF and HF of the patients before and after adjustment for TBS. The proportion of patients needed a therapeutic intervention significantly increased from 17.1 to 25.7 after TBS adjustment of FRAX. Conclusion. Adjustment of FRAX with TBS will reclassify the treatment decision in a considerable number of kidney transplant recipients. This clinical value warrants the adjustment of FRAX data with TBS in future workouts. © 2020, Iranian Society of Nephrology. All rights reserved

An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients

Background: Predicting the response of inflammatory bowel disease (IBD) patients to infliximab (IFX) is an unmet clinical need. The expression and density of transmembrane tumor necrosis factor-α in circulating leukocytes maybe directly related to response by promoting apoptosis. Aim: We tested the hypothesis that direct apoptosis assessment by real-time polymerase chain reaction evaluation of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins in peripheral blood mononuclear cells (PBMCs) might be associated with response to IFX. Methods: IFX naïve patients (Crohn�s disease, 32 and ulcerative colitis, 20; 35 responders and 17 non-responders) were evaluated for Bax and Bcl-2 mRNA expression levels before and 2 weeks after the first infusion. In a subset of patients, apoptosis was also evaluated using flow cytometry. Results: After the first infusion, Bax increased more in responders than in non-responders (0.7± 0.38 vs 0.81 ± 0.32 and 0.86 ± 0.37 vs 0.87 ± 0.45, respectively, p = 0.071). Bcl-2 decreased more in responders than in non-responders (0.71 ± 0.12 vs 0.63 ± 0.13 and 0.81 ± 0.28 vs 0.77 ± 0.27, respectively, p = 0.038). The Bax/Bcl-2 ratio increased more in responders than in non-responders (0.99 ± 0.5 vs 1.3 ± 0.51 and 1.03 ± 0.17 vs 1.1 ± 0.28, respectively, p = 0.005). The Bax/Bcl-2 ratio was able to predict response in 33/52 patients and was correlated to flow cytometry-assessed apoptosis (r = 0.911; p < 0.001). Conclusions: An increased Bax/Bcl-2 ratio in PBMCs was associated with therapeutic response to IFX in IBD patients. © Author(s) 2018

Evaluation of circulating cellular DCLK1 protein, as the most promising colorectal cancer stem cell marker, using immunoassay based methods

BACKGROUND: DCLK1, as the most potential colorectal cancer stem cell (CSC) marker has been the core of many recent investigations. However, no study has been performed to evaluate the circulating cellular DCLK1 protein (CCDP) that might reflect the presences of colorectal CSC in circulation. OBJECTIVES: We aimed to evaluate CCDP in the peripheral blood mononuclear cells (PBMCs) of colorectal cancer (CRC) patients applying immunoassay based methods including PLA, IPCR and ELISA in order to introduce the method of choice for clinical detection of CCDP. METHODS: PBMCs were extracted from blood samples of 58 CRC patients along with 58 blood samples of tumor free controls. Total protein of PBMC was extracted and the CCDP level was evaluated. The results of three applied immunoassay tests were compared and the best approach for clinical application was introduced, accordingly. In addition, the correlation of CCD Plevel with clincopathologic findings of CRC patients was assessed. RESULTS: The results of three immuneassay methods confirmed each other. Based on our finding, ELISA could be the most judicious method for clinical evaluation of CCDP considering its simplicity for clinical implications. Our results also showed a significant higher amount of CCDP in peripheral blood of CRC patients compared to control group which was also correlated with patients' clinicopathologic finding such as stage, grade and neoadjuvant history. CONCLUSION: CCDP could be applied for monitoring purposes in CRC patients. However, its application needs to be more elucidated in future investigations implementing larger samples. © 2016 - IOS Press and the authors

An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients

Background: Predicting the response of inflammatory bowel disease (IBD) patients to infliximab (IFX) is an unmet clinical need. The expression and density of transmembrane tumor necrosis factor-α in circulating leukocytes maybe directly related to response by promoting apoptosis. Aim: We tested the hypothesis that direct apoptosis assessment by real-time polymerase chain reaction evaluation of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins in peripheral blood mononuclear cells (PBMCs) might be associated with response to IFX. Methods: IFX naïve patients (Crohn�s disease, 32 and ulcerative colitis, 20; 35 responders and 17 non-responders) were evaluated for Bax and Bcl-2 mRNA expression levels before and 2 weeks after the first infusion. In a subset of patients, apoptosis was also evaluated using flow cytometry. Results: After the first infusion, Bax increased more in responders than in non-responders (0.7± 0.38 vs 0.81 ± 0.32 and 0.86 ± 0.37 vs 0.87 ± 0.45, respectively, p = 0.071). Bcl-2 decreased more in responders than in non-responders (0.71 ± 0.12 vs 0.63 ± 0.13 and 0.81 ± 0.28 vs 0.77 ± 0.27, respectively, p = 0.038). The Bax/Bcl-2 ratio increased more in responders than in non-responders (0.99 ± 0.5 vs 1.3 ± 0.51 and 1.03 ± 0.17 vs 1.1 ± 0.28, respectively, p = 0.005). The Bax/Bcl-2 ratio was able to predict response in 33/52 patients and was correlated to flow cytometry-assessed apoptosis (r = 0.911; p < 0.001). Conclusions: An increased Bax/Bcl-2 ratio in PBMCs was associated with therapeutic response to IFX in IBD patients. © Author(s) 2018