New long noncoding RNA biomarkers and ceRNA networks on miR-616-3p in colorectal cancer: Bioinformatics-based study.

Background: Cancer development is aided by the role of long noncoding RNAs (lncRNAs) that act as competing endogenous RNAs (ceRNAs) absorbing microRNAs (miRNAs). We aimed to discover a novel regulatory axis in colorectal cancer (CRC) and potential biomarkers based on miR-616-3p. Materials and Methods: The gene expression omnibus database was mined for differentially expressed lncRNAs (DELs) and mRNAs. LncRNAs and mRNAs were predicted using the RegRNA and TargetScan databases. A combination of the ciBioPortal and Ensemble databases was used to locate the mRNAs. Cytoscape 3.7.1-built CeRNA networks. A quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to confirm the expression levels of these RNA molecules. Statistical analyses were implemented by GraphPad Prism 9. Results: qRT-PCR showed (Linc01282, lnc-MYADM-1:1, and Zinc Finger Protein 347 [ZNF347]) were overexpressed whereas, (salt-inducible kinases 1 [SIK1], and miR-616-3p) were down regulated. Conclusion: These results identify unique, unreported lncRNAs as CRC prognostic biomarkers, as well as prospective mRNAs as new treatment targets and predictive biomarkers for CRC. In addition, our study uncovered unexplored ceRNA networks that should be studied further in CRC.

Trend of the polyp and adenoma detection rate by sex and age in asymptomatic average-risk and high-risk individuals undergoing screening colonoscopy, 2012-2019.

Adenoma detection rate (ADR) is an imperative quality measure for colorectal cancer (CRC) screening. This retrospective observational study aimed to determine the trend of polyp detection rate (PDR) and ADR in asymptomatic average- and high-risk participants in different age groups who underwent screening colonoscopy over the seven years from April 2012 to March 2019 in a tertiary gastroenterology referral center of Iran. Of 1676 participants, 51.8 % were men (mean age 52.3 years). The overall PDR and ADR were 22.7 %, and 13.5 %, respectively. Both Polyps and adenomas were more common in age groups 51-59 and ≥60 years in high-risk patients than in the corresponding groups of average-risk patients (p < 0.05). Also, both PDR and ADR were more frequent in men than in women among all studied age groups, but it was statistically significant only for the youngest age group (16.8 % versus 10.5 %, p < 0.05) for PDR and the oldest age group (19.7 % versus 13 %, p < 0.05) for ADR, respectively. The trend of total ADR was upward over 7 years in both average-risk (6.7 % to 13.3 %) and high-risk (9.8 % to 27 %) groups and across all age groups in both sexes. Multivariable logistic regression revealed that high-risk individuals had an elevated risk of adenoma compared with average-risk patients (OR: 1.6, p = 0.006). Substantial variation in thresholds of polyp and adenoma detection by age, sex, and risk categories emphasizes the need for a risk-adapted approach to CRC screening and prevention programs.

Constructing a novel competing Endogenous RNAs network based on NR3C1 and X-linked inhibitor of apoptosis protein genes reveals potential prognostic biomarkers in colorectal cancer.

Background: Long noncoding RNAs (lncRNAs) have been recognized as the main modulatory molecules in various cancers and perform as competing endogenous RNAs (ceRNAs). The nuclear hormone receptor superfamily of ligand-activated transcription factors (NR3C1) regulates numerous proliferative and metabolic processes such as tumorigenesis and metabolic diseases. Furthermore, X-linked inhibitor of apoptosis protein (XIAP) belongs to a family of the inhibitors of apoptosis proteins, is located downstream of the glucocorticoid receptor (GR or NR3C1) pathway, and cooperates with GR to suppress apoptosis. However, the underlying mechanisms of NR3C1 and XIAP in colorectal cancer (CRC) remain mainly unclear. This research aims to clarify the potential RNA biomarkers and to construct a novel ceRNA network in CRC. Materials and Methods: Multistep bioinformatics methods such as Lnc2cancer and miRDB databases were applied to identify candidate lncRNAs and miRNAs. The interaction energy between lncRNAs, NR3C1, and XIAP genes was analyzed by the LncRRIsearch database. Plus, microRNAs and lncRNA were evaluated via the Diana tools database to select microRNAs with the most binding scores. Quantitative reverse transcription-polymerase chain reaction (QRT-PCR) was applied to verify RNA molecules' expression levels and their association with the clinicopathological factors in 30 CRC tissues compared to 30 adjacent tissues. Results: QRT-PCR showed upregulation of KCNQ1OT1, NR3C1, and XIAP and downregulation of miR-421. The ceRNA network was constructed with 17 lncRNAs, 2 mRNAs, and 42 miRNAs. Thus, we explained the potential interactions between KCNQ1OT1 and miR-421 with NR3C1 and XIAP genes. Conclusion: Our study represents potential prognostic biomarkers and a new ceRNA network for further study in CRC.

High claudin-4 antigen expression in triple-negative breast cancer by the immunohistochemistry method.

Background: Triple-negative breast cancer is a heterogeneous subtype of breast cancer. Claudin is an epithelial tight junctional protein, and also it is a receptor for clostridium perfringens enterotoxin and shows impairment of expression in several cancers. The chief purpose of this study is to assess the claudin-4 expression in triple-negative breast cancer (TNBC) Iranian patients and evaluate its correlation with some clinicopathological factors. Materials and Methods: In this study, 81 TNBC patients were evaluated for the claudin-4 expression by immunohistochemistry. The slides' staining intensity was examined and scored from 0 to 3. Then, slides were reviewed to assess the percentage of cells with membrane and cytoplasmic staining; the obtaining scores were 1-4. Finally, added the resulting two numbers from two stages, and the final number was a maximum of 7. Final scores of 0-3 were considered the low expression, and 4-7 were considered the high expression. Finally, the collected data were analyzed using the Chi-square test. Results: Eighty-one women with breast cancer and a mean age of 49 ± 12 years participated in the study. In 80% of the patients, there was a high expression of claudin-4 marker, and 20% had low expression. The expression level of the marker was not significantly correlated with age, tumor size, lymph node involvement, tumor grade, disease stage, Ki-67, and metastasis. Conclusion: The present study confirmed the high frequency of claudin-4 antigen expression in TNBC patients, and no significant correlation was observed between the expression of antigen and demographic or clinicopathological factors.

Androgen Receptor Expression and Its Correlation with Clinicopathological Parameters in Iranian Patients with Triple Negative Breast Cancer.

BACKGROUND & OBJECTIVE: Our knowledge about correlation of androgen receptor expression and clinicopathological properties of triple-negative breast cancer (TNBC) patients is inadequate, particularly in the Iranian population. The main aim of the present study was to assess the AR expression in TNBC Iranian patients and evaluate its correlation with their clinicopathological parameters. METHODS: Herein, 76 TNBC patients were evaluated for the AR expression by immunohistochemistry. The slides' staining intensity was investigated according to the average degree of nuclear staining and sub-classified into negative (0), weak (1), moderate (2), or strong (3). Subsequently, the positive cells percentage for each slide was assessed and sub-classified into <25% (1), 25-50% (2), 50-75% (3), and >75% (4). The aggregation of these two scores was used as the final score ranging from 0 to 7. While 4-7 scores were selected as positive, the others were included in the AR-negative expression group. Fisher's exact test was used to analyze the AR expression correlation with the clinicopathological parameters. RESULTS: Positive immunoreactivity for AR was observed in 8 out of 76 (11%) specimens. No-correlation (P>0.05) was observed between the AR expression and grade, stage, lymph node status, and Ki-67 level. The AR-positive patients exhibited older age at the time of diagnosis (P=0.0339) and larger tumor size (P=0.0224) in comparison with the AR-negative patients. Low percentage of TNBC patients expressed AR and no significant correlation was observed between its expression and most of the clinicopathological parameters. CONCLUSION: AR may not be a suitable biomarker and treatment target for the Iranian patients with TNBC.

Prolactin receptor expression as a novel prognostic biomarker for triple negative breast cancer patients.

Prolactin receptor (PRLR) is a novel emerging prognostic biomarker in different cancers, especially in breast cancer. However, there is limited information about the association of PRLR expression and triple-negative breast cancers (TNBC) prognosis. In this study, 80 TNBC patients were evaluated for PRLR expression by immunohistochemistry. The correlation of PRLR expression with clinicopathological features, patient recurrence, and survival was investigated. PRLR expression was considered positive if >10% of tumor cells were stained. The Fisher's exact test was used to analyze PRLR expression relation with the clinicopathological parameters. Survival distribution was estimated by the Kaplan-Meier method. Positive immunoreactivity for PRLR was observed in 50 out of 80 (62%) specimens. Although expression of PRLR was associated with TNBC patients' stage, no-correlation was observed between its expression and tumor size, grade, lymph node status, and Ki-67 expression. In addition, patients with positive expression of PRLR exhibited lower recurrence (P = 0.0027) and higher overall survival (P = 0.0285) in comparison with negative expression group. In multivariate analyses, positive expression of PRLR was an independent prognostic marker for lower recurrence (P < 0.001) and higher overall survival (P < 0.001). Therefore, PRLR plays a crucial role in TNBC and has to be considered as an independent prognostic biomarker for TNBC patients.

Paraben Content in Adjacent Normal-malignant Breast Tissues from Women with Breast Cancer.

OBJECTIVE: Accumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life. To assess the role of parabens in this phenomenon, the paraben content of adjacent normal-malignant breast tissues is measured in women with breast cancer living in Isfahan Province, Iran. METHODS: Adjacent normal-malignant breast tissue samples were obtained from 53 subjects. The parabens including methyl-paraben (MePB), ethyl-paraben (EtPB), propyl-paraben (PrPB), and butylparaben (BuPB) were extracted from the sample supernatant and then subjected to gas chromatography analysis. RESULTS: Some risk factors for breast cancer were stimulated by parabens in adjacent malignant-normal breast tissues among young and middle-aged women with breast cancer. We observed a significant association for dose-response pattern of MePB [OR = 98.34 (11.43-185.2), P = 0.027] for both ER+ and PR+ women and MePB [OR = 164.3 (CI: 112.3-216.3), P < 0.001] for HER2+ women than women with negative receptors. The risk of 95-fold increase in MePB dose and 164-fold increase in ΣPBs dose were significant for women with hereditary breast cancer in first-degree relatives. CONCLUSION: These results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.