The Utility of SOX2 and AGR2 Biomarkers as Early Predictors of Tamoxifen Resistance in ER-Positive Breast Cancer Patients

Background. Despite the undeniable benefit of tamoxifen therapy for ER-positive breast cancer patients, approximately one-third of those patients either do not respond to tamoxifen or develop resistance. Thus, it is a crucial step to identify novel, reliable, and easily detectable biomarkers indicating resistance to this drug. Objective. The aim of this work is to explore SOX2 and AGR2 biomarker expression in the tumor tissue of ER-positive breast cancer patients in combination with the evaluation of serum AGR2 level of these patients in order to validate these biomarkers as early predictors of tamoxifen resistance. Methods. This study was conducted on 224 ER-positive breast cancer patients. All patients were primarily subjected to serum AGR2 levelling by ELISA and their breast cancer tissue immunostained for SOX2 and AGR2. After 5 years of follow-up, the patients were divided into 3 groups: group 1 was tamoxifen sensitive and groups 2 and 3 were tamoxifen resistant. Time to failure of tamoxifen treatment was considered the time from the beginning of tamoxifen therapy to the time of discovery of breast cancer recurrence or metastases (in months). Results. SOX2 and AGR2 biomarkers expression and serum AGR2 level were significantly higher in groups 2 and 3 in comparison to group 1, while the relationship between Her2 neu expression and Ki67 index in the 3 different groups was statistically nonsignificant. Lower SOX2 and AGR2 expression and low AGR2 serum levels in the studied patients of groups 2 and 3 were significantly associated with longer time-to-failure of tamoxifen treatment. According to the ROC curve, the combined use of studied markers validity was with a sensitivity of 100%, specificity of 96%, PPV 96%, and NPV 100% (p<0.001; AUC: 0.984). Conclusions. Integrated use of SOX2 and AGR2 biomarkers with serum AGR2 assay holds a promising hope for their future use as predictive markers for early detection of tamoxifen resistance in ER-positive breast cancer patients

Predictive value of serum YKL-40, interleukin-37, and cancer antigen 125 panel in noninvasive staging of endometriosis

Background: The diagnosis of advanced endometriosis remains challenging with considerable limitations in the diagnosis of retroperitoneal and deep infiltrating lesions. Thus, a well-defined panel of inexpensive, noninvasive inflammatory biomarkers could be a crucial tool for appropriate staging for women with suspected endometriosis. The aim of this work is to explore the potential use of serum YKL-40, interleukin-37 (IL-37), and cancer antigen 125 (CA125) for noninvasive staging of endometriosis patients for proper intervention and most optimal management of the condition. Methods: This study was conducted on 90 women, who had undergone laparoscopic or laparotomy surgery due to suspected pelvic endometriosis. Blood samples for serum YKL-40, IL-37, and CA125 levels assay were taken from all participants at admission for laparoscopy or laparotomy. After histopathological confirmation of the diagnosis, the selected cases were immunostained for YKL-40, IL-37, and CA125. Results: YKL-40, IL-37, and CA125 serum levels were significantly elevated in patients with endometriosis than healthy controls. Moreover, the association between the serum level and immunoexpression and grading of endometriosis. A triple combination panel of serum YKL-40, IL-37, and CA125 was found to have the best sensitivity and specificity (96.67% and 100.0%, respectively) compared to any single serum marker alone or double combination panel in predicting the severity of endometriosis. Conclusions: A triple combination panel of serum YKL-40, IL-37, and CA125 could be used in the future for predicting endometriosis stage, providing a practical reference for making better-informed decisions on the best treatment plan

Genotypic Characterization of Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Isolated from an Egyptian University Hospital

Globally, Klebsiella pneumoniae (K. pneumoniae) has been identified as a serious source of infections. The objectives of our study were to investigate the prevalence of multidrug-resistant (MDR) K. pneumoniae in Tanta University Hospitals, Gharbia Governorate, Egypt; characterize their carbapenem resistance profiles; and identify their different capsular serotypes. We identified and isolated 160 (32%) K. pneumoniae from 500 different clinical samples, performed antimicrobial susceptibility testing, and then used multiplex PCR to detect carbapenemase genes and capsular serotypes K1, K2, K3, K5, K20, K54, and K57. We detected phenotypic carbapenem resistance in 31.3% (50/160) of the isolates; however, molecular assays revealed that 38.75% (62/160) of isolates were carrying carbapenemase-encoding genes. Generally, blaOXA-48 was the prevalent gene (15.5%), followed by blaVIM (15%), blaIMP (7.5%), blaKPC (4%), and blaNDM (3.8%). BlaVIM and blaOXA-48 correlated with phenotypic resistance in 91.67% and 88% of the isolates that harbored them, respectively. Capsular typing showed that the most prevalent pathotype was K1 (30.6%), followed by K57 (24.2%), K54 (19.35%), K20 (9.67%), and K2 (6.45%). A critical risk to community health is posed by the high incidence of multidrug-resistant (MDR) virulent K. pneumoniae isolates from our hospital, and our study examines this pathogen’s public health and epidemiological risks