Expression and Clinical Significance of ki-67, CD10, BCL6, MUM1, c-MYC, and EBV in Diffuse Large B Cell Lymphoma Patients.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults. Although studies regarding the association between the expression of Ki-67, CD10, BCL6, and MUM1 proteins, as well as c-MYC amplification and EBV status with clinicopathologic characteristics have rapidly progressed, their co-expression and prognostic role remain unsatisfactory. Therefore, this study aimed to investigate the association between the expression of all markers and clinicopathologic features and their prognostic value in DLBCL. Also, the co-expression of markers was investigated. METHODS: The protein expression levels and prognostic significance of Ki-67, CD10, BCL6, and MUM1 were investigated with clinical follow-up in a total of 53 DLBCL specimens (including germinal center B [GCB] and activated B cell [ABC] subtypes) as well as adjacent normal samples using immunohistochemistry (IHC). Besides, the clinical significance and prognostic value of c-MYC and EBV status were also evaluated through chromogenic in situ hybridization (CISH), and their correlation with other markers was also assessed. RESULTS: The results demonstrated a positive correlation between CD10 and BCL6 expression, with both markers being associated with the GCB subtype (P<0.001 and P=0.001, respectively). Besides, we observe a statistically significant association between MUM1 protein expression and clinicopathologic type (P<0.005) as well as a positive association between c-MYC and recurrence (P=0.028). Our survival analysis showed that patients who had responded to R-CHOP treatment had better overall survival (OS) and progression-free survival (PFS) than those who did not. CONCLUSION: Collectively, this study's results add these markers' value to the existing clinical understanding of DLBCL. However, further investigations are needed to explore markers' prognostic and biological roles in DLBCL patients.

Aptamers as an approach to targeted cancer therapy.

Conventional cancer treatments can cause serious side effects because they are not specific to cancer cells and can damage healthy cells. Aptamers often are single-stranded oligonucleotides arranged in a unique architecture, allowing them to bind specifically to target sites. This feature makes them an ideal choice for targeted therapeutics. They are typically produced through the systematic evolution of ligands by exponential enrichment (SELEX) and undergo extensive pharmacological revision to modify their affinity, specificity, and therapeutic half-life. Aptamers can act as drugs themselves, directly inhibiting tumor cells. Alternatively, they can be used in targeted drug delivery systems to transport drugs directly to tumor cells, minimizing toxicity to healthy cells. In this review, we will discuss the latest and most advanced approaches to using aptamers for cancer treatment, particularly targeted therapy overcoming resistance to conventional therapies.

Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors.

DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. Several studies showed that the dysregulation of DDIT4 is involved in different malignancies with paradoxical expressions and roles. Therefore, this study investigated the clinical significance, prognostic, and diagnostic value of DDIT4 in different types of pancreatic tumors (PT). The expression of DDIT4 and long non-coding RNA (TPTEP1) in mRNA level was examined in 27 fresh PT samples using Real-time quantitative PCR (RT-qPCR). Moreover, 200 formalin-fixed paraffin-embedded PT tissues, as well as 27 adjacent normal tissues, were collected to evaluate the clinical significance, prognostic, and diagnosis value of DDIT4 expression by immunohistochemistry (IHC) on tissue microarrays (TMA) slides. The results of RT-qPCR showed that the expression of DDIT4 in tumor samples was higher than in normal samples which was associated with high tumor grade (P = 0.015) and lymphovascular invasion (P = 0.048). Similar to this, IHC findings for nucleus, cytoplasm, and membrane localization showed higher expression of DDIT4 protein in PT samples rather than in nearby normal tissues. A statistically significant association was detected between a high level of nuclear expression of DDIT4 protein, and lymphovascular invasion (P = 0.025), as well as advanced TNM stage (P = 0.034) pancreatic ductal adenocarcinoma (PDAC) and in pancreatic neuroendocrine tumor (PNET), respectively. In contrast, a low level of membranous expression of DDIT4 protein showed a significant association with advanced histological grade (P = 0.011), margin involvement (P = 0.007), perineural invasion (P = 0.023), as well as lymphovascular invasion (P = 0.005) in PDAC. No significant association was found between survival outcomes and expression of DDIT4 in both types. It was found that DDIT4 has rational accuracy and high sensitivity as a diagnostic marker. Our results revealed a paradoxical role of DDIT4 expression protein based on the site of nuclear and membranous expression. The findings of this research indicated that there is a correlation between elevated nuclear expression of DDIT4 and the advancement and progression of disease in patients with PT. Conversely, high membranous expression of DDIT4 was associated with less aggressive tumor behavior in patients with PDAC. However, further studies into the prognostic value and biological function of DDIT4 are needed in future studies.

High expression of Talin-1 is associated with tumor progression and recurrence in melanoma skin cancer patients.

BACKGROUND: Talin-1 as a component of multi-protein adhesion complexes plays a role in tumor formation and migration in various malignancies. This study investigated Talin-1 in protein levels as a potential prognosis biomarker in skin tumors. METHODS: Talin-1 was evaluated in 106 skin cancer (33 melanomas and 73 non-melanomas skin cancer (NMSC)) and 11 normal skin formalin-fixed paraffin-embedded (FFPE) tissue samples using immunohistochemical technique on tissue microarrays (TMAs). The association between the expression of Talin-1 and clinicopathological parameters, as well as survival outcomes, were assessed. RESULTS: Our findings from data minings through bioinformatics tools indicated dysregulation of Talin-1 in mRNA levels for skin cancer samples. In addition, there was a statistically significant difference in Talin-1 expression in terms of intensity of staining, percentage of positive tumor cells, and H-score in melanoma tissues compared to NMSC (P = 0.001, P < 0.001, and P < 0.001, respectively). Moreover, high cytoplasmic expression of Talin-1 was found to be associated with significantly advanced stages (P = 0.024), lymphovascular invasion (P = 0.023), and recurrence (P = 0.006) in melanoma cancer tissues. Our results on NMSC showed a statistically significant association between high intensity of staining and the poor differentiation (P = 0.044). No significant associations were observed between Talin-1 expression levels and survival outcomes of melanoma and NMSC patients. CONCLUSION: Our observations showed that higher expression of Talin1 in protein level may be significantly associated with more aggressive tumor behavior and advanced disease in patients with skin cancer. However, further studies are required to find the mechanism of action of Talin-1 in skin cancers.

Flavonoids nanostructures promising therapeutic efficiencies in colorectal cancer.

Colorectal cancer is among the frequently diagnosed cancers with high mortality rates around the world. Polyphenolic compounds such as flavonoids are secondary plant metabolites which exhibit anti-cancer activities along with anti-inflammatory effects. However, due to their hydrophobicity, sensitivity to degradation and low bioavailability, therapeutic effects have shown poor therapeutic effect. Nano delivery systems such as nanoliposomes, nanomicelles, silica nanoparticles have been investigated to overcome these difficulties. This review provides a summary of the efficiency of certain flavonoids and polyphenols (apigenin, genistein, resveratrol, quercetin, silymarin, catechins, luteolin, fisetin, gallic acid, rutin, and curcumin) on colorectal cancer models. It comprehensively discusses the influence of nano-formulation of flavonoids on their biological functions, including cellular uptake rate, bioavailability, solubility, and cytotoxicity, as well as their potential for reducing colorectal cancer tumor size under in vivo situations.

Prognostic value of Talin-1 in renal cell carcinoma and its association with B7-H3.

METHODS: Talin-1 protein was demonstrated as a potential prognostic marker in renal cell carcinoma (RCC) using bioinformatics analysis. We, therefore, examined the protein expression levels and prognostic significance of Talin-1 with a clinical follow-up in a total of 269 tissue specimens from three important subtypes of RCC and 30 adjacent normal samples using immunohistochemistry. Then, we used combined analysis with B7-H3 to investigate higher prognostic values. RESULTS: The results showed that high membranous and cytoplasmic expression of Talin-1 was significantly associated with advanced nucleolar grade, microvascular invasion, histological tumor necrosis, and invasion to Gerota's fascia in clear cell RCC (ccRCC). In addition, high membranous and cytoplasmic expression of Talin-1 was found to be associated with significantly poorer disease-specific survival (DSS) and progression-free survival (PFS). Moreover, increased cytoplasmic expression of Talin-1High/B7-H3High compared to the other phenotypes was associated with tumor aggressiveness and progression of the disease, and predicted a worse clinical outcome, which may be an effective biomarker to identify ccRCC patients at high risk of recurrence and metastasis. CONCLUSIONS: Collectively, these observations indicate that Talin-1 is an important molecule involved in the spread and progression of ccRCC when expressed particularly in the cytoplasm and may serve as a novel prognostic biomarker in this subtype. Furthermore, a combined analysis of Talin-1/B7-H3 indicated an effective biomarker to predict the progression of disease and prognosis in ccRCC.

Copy Number Variation of Circulating Tumor DNA (ctDNA) Detected Using NIPT in Neoadjuvant Chemotherapy-Treated Ovarian Cancer Patients.

Analysis of circulating tumor DNA (ctDNA) can be used to characterize and monitor cancers. Recently, non-invasive prenatal testing (NIPT) as a new next-generation sequencing (NGS)-based approach has been applied for detecting ctDNA. This study aimed to investigate the copy number variations (CNVs) utilizing the non-invasive prenatal testing in plasma ctDNA from ovarian cancer (OC) patients who were treated with neoadjuvant chemotherapy (NAC). The plasma samples of six patients, including stages II-IV, were collected during the pre- and post-NAC treatment that were divided into NAC-sensitive and NAC-resistant groups during the follow-up time. CNV analysis was performed using the NIPT via two methods "an open-source algorithm WISECONDORX and NextGENe software." Results of these methods were compared in pre- and post-NAC of OC patients. Finally, bioinformatics tools were used for data mining from The Cancer Genome Atlas (TCGA) to investigate CNVs in OC patients. WISECONDORX analysis indicated fewer CNV changes on chromosomes before treatment in the NAC-sensitive rather than NAC-resistant patients. NextGENe data indicated that CNVs are not only observed in the coding genes but also in non-coding genes. CNVs in six genes were identified, including HSF1, TMEM249, MROH1, GSTT2B, ABR, and NOMO2, only in NAC-resistant patients. The comparison of these six genes in NAC-resistant patients with The Cancer Genome Atlas data illustrated that the total alteration frequency is amplification, and the highest incidence of the CNVs (≥35% based on TCGA data) is found in MROH1, TMEM249, and HSF1 genes on the chromosome (Chr) 8. Based on TCGA data, survival analysis showed a significant reduction in the overall survival among chemotherapy-resistant patients as well as a high expression level of these three genes compared to that of sensitive samples (all, p < 0.0001). The continued Chr8 study using WISECONDORX revealed CNV modifications in NAC-resistant patients prior to NAC therapy, but no CNV changes were observed in NAC-sensitive individuals. Our findings showed that low coverage whole-genome sequencing analysis used for NIPT could identify CNVs in ctDNA of OC patients before and after chemotherapy. These CNVs are different in NAC-sensitive and -resistant patients highlighting the potential application of this approach in cancer patient management.

Overexpression of cytoplasmic dynamin 2 is associated with worse outcomes in patients with clear cell renal cell carcinoma.

BACKGROUND: Dynamin 2 (DNM2) involved in tumor progression in various malignancies. OBJECTIVE: For the first time, we evaluated DNM2 expression pattern, its association with clinicopathological characteristics and survival outcomes in RCC subtypes. METHODS: We evaluated the DNM2 expression pattern in RCC tissues as well as adjacent normal tissue using immunohistochemistry on tissue microarray (TMA) slides. RESULTS: Our findings revealed increased DNM2 expression in RCC samples rather than in adjacent normal tissues. The results indicated that there was a statistically significant difference between cytoplasmic expression of DNM2 among subtypes of RCC in terms of intensity of staining, percentage of positive tumor cells, and H-score (P= 0.024, 0.049, and 0.009, respectively). The analysis revealed that increased cytoplasmic expression of DNM2 in ccRCC is associated with worse OS (log rank: P= 0.045), DSS (P= 0.049), and PFS (P= 0.041). Furthermore, cytoplasmic expression of DNM2 was found as an independent prognostic factor affecting DSS and PFS in multivariate analysis. CONCLUSIONS: Our results indicated that DNM2 cytoplasmic expression is associated with tumor aggressiveness and poor outcomes. DNM2 could serve as a promising prognostic biomarker and therapeutic target in patients with ccRCC.

Co-expression of cancer stem cell markers, SALL4/ALDH1A1, is associated with tumor aggressiveness and poor survival in patients with serous ovarian carcinoma.

BACKGROUND: Spalt-like transcription factor 4 (SALL4) and aldehyde dehydrogenase1 family member A1 (ALDH1A1) expressing cells have been characterized as possessing stem cell-like properties known as cancer stem cell marker in serous ovarian carcinoma (SOC). METHODS: The association between SALL4 and ALDH1A1 was observed based on literature review and bioinformatics tools. Therefore, this study aimed to investigate the association between the co-expression of SALL4/ALDH1A1 proteins and clinicopathological parameters and their prognostic value in SOC patients using immunohistochemical staining on tissue microarrays (TMAs). Furthermore, benign tumors and normal tissue samples were compared with the expression of the tumor tissue samples. RESULTS: Increased co-expression of SALL4/ALDH1A1 was found to be significantly associated with the advanced FIGO stage (P = 0.047), and distant metastasis (P = 0.028). The results of Kaplan-Meier survival analysis indicated significant differences between disease- specific survival (DSS; P = 0.034) or progression-free survival (PFS; P = 0.018) and the patients with high and low co-expression of SALL4/ALDH1A1, respectively. Furthermore, high level co-expression of SALL4/ALDH1A1 was a significant predictor of worse DSS and PFS in the univariate analysis. The data also indicated that the co-expression of SALL4/ALDH1A1 was an independent prognostic factor affecting PFS. Moreover, the co-expression of SALL4/ALDH1A1 added prognostic values of DSS in patients with SOC who had grade III versus grade I in multivariate analysis. CONCLUSIONS: Our data demonstrated that high co-expression of SALL4/ALDH1A1 was found to be significantly associated with tumor aggressiveness and worse DSS or PFS in SOC patients. Therefore, co-expression of SALL4/ALDH1A1 may serve as a potential prognostic biomarker of cancer progression in these cases.

Relationship Between Low Expressions of tRNA-Derived Fragments with Metastatic Behavior of Colorectal Cancer.

PURPOSE: Colorectal cancer (CRC) is one of the most commonly diagnosed malignant tumors and highly heterogeneous diseases. More recently, RNA expression profiles have been used as prognostic cancer markers. In this regard, the expression of small non-coding RNAs like tRNA-derived fragments (tRFs) in tumor tissue has potential diagnostic values in metastatic cancer. METHOD: Sixty postoperative CRC tissue samples, consisting of 30 cancers and 30 adjacent normal tissues, were collected from cancer patients. We evaluated MINTbase database to select tRNA-derived fragments. The expression levels of miR-1280, miR1308, tRNA-ValAAC/CAC, and tRNA-AspGTC were measured by TaqMan quantitative reverse transcription PCR technology. Also, we have evaluated the correlation between the levels of tRFs gene expression and clinicopathological of CRC disease. RESULT: The three tRFs derived from tRF/miR-1280, tRNA-ValAAC/CAC, and tRNA-AspGTC downregulated in tumor tissues (all, p < 0.0001). These tRFs have lower expression in stage IV in comparison with stage III. The tRFs derived from tRNA-ValAAC (p = 0.005) and tRNA-AspGTC (p = 0.034) showed the decreased expression in CRC patients with distant metastasis. CONCLUSION: The present study demonstrated that low expression of tRF/miR-1280, tRNA-ValAAC/CAC, and tRNA-AspGTC was significantly associated with metastatic stage and more aggressive tumor behavior of CRC disease. Our finding promising the potential of using tRFs as biomarkers for cancer diagnosis.

Overexpression of melanoma-associated antigen A2 has a clinical significance in embryonal carcinoma and is associated with tumor progression.

INTRODUCTION: Melanoma-associated antigen A2 (MAGE-A2) is a member of the cancer-testis antigen family differentially overexpressed in a variety of malignancies and is associated with tumor development. However, clinical significance and prognostic value of MAGE-A2 in different histological subtypes of testicular germ cell tumors (TGCTs) have not been explored. MATERIALS AND METHODS: Here, we aimed to investigate the clinical significance and prognostic impact of MAGE-A2 expression in TGCTs compared to benign tumors as well as adjacent normal tissues and then between seminomas and non-seminomas groups using immunohistochemistry on tissue microarrays. RESULTS: The results indicated a statistically significant difference between overexpression of MAGE-A2 and histological subtypes of TGCTs. A statistically significant association was found between a high level of nuclear expression of MAGE-A2 protein and advanced pT stage (P = 0.022), vascular invasion (P = 0.037), as well as involvement of rete testis (P = 0.022) in embryonal carcinomas. Increased nuclear expression of MAGE-A2 was observed to be associated with more aggressive behaviors and tumor progression rather than cytoplasmic expression in these cases. Further, high level nuclear expression of MAGE-A2 had shorter disease-specific survival (DSS) or progression-free survival (PFS) compared to patients with moderate and low expression of MAGE-A2, however, without a statistically significant association. CONCLUSION: Our results confirm that increased nuclear expression of MAGE-A2 has a clinical significance in embryonal carcinomas and is associated with progression of disease. Moreover, MAGE-A2 may act as a potential predictive biomarker for the prognosis in embryonal carcinomas if follow-up period becomes longer. Further investigations for the biological function of MAGE-A2 are required in future studies.

High expression of DNA damage-inducible transcript 4 (DDIT4) is associated with advanced pathological features in the patients with colorectal cancer.

DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. This study was conducted to investigate expression and prognostic significance of DDIT4 protein as a biomarker in the patients with colorectal cancer (CRC). PPI network and KEGG pathway analysis were applied to identify hub genes among obtained differentially expressed genes in CRC tissues from three GEO Series. In clinical, expression of DDIT4 as one of hub genes in three subcellular locations was evaluated in 198 CRC tissues using immunohistochemistry method on tissue microarrays. The association between DDIT4 expression and clinicopathological features as well as survival outcomes were analyzed. Results of bioinformatics analysis indicated 14 hub genes enriched in significant pathways according to KEGG pathways analysis among which DDIT4 was selected to evaluate CRC tissues. Overexpression of nuclear DDIT4 protein was found in CRC tissues compared to adjacent normal tissues (P = 0.003). Furthermore, higher nuclear expression of DDIT4 was found to be significantly associated with the reduced tumor differentiation and advanced TNM stages (all, P = 0.009). No significant association was observed between survival outcomes and nuclear expression of DDIT4 in CRC cases. Our findings indicated higher nuclear expression of DDIT4 was significantly associated with more aggressive tumor behavior and more advanced stage of disease in the patients with CRC.

Overexpression of DDIT4 and TPTEP1 are associated with metastasis and advanced stages in colorectal cancer patients: a study utilizing bioinformatics prediction and experimental validation.

BACKGROUND: Various diagnostic and prognostic tools exist in colorectal cancer (CRC) due to multiple genetic and epigenetic alterations causing the disease. Today, the expression of RNAs is being used as prognostic markers for cancer. METHODS: In the current study, various dysregulated RNAs in CRC were identified via bioinformatics prediction. Expression of several of these RNAs were measured by RT-qPCR in 48 tissues from CRC patients as well as in colorectal cancer stem cell-enriched spheroids derived from the HT-29 cell line. The relationships between the expression levels of these RNAs and clinicopathological features were analyzed. RESULTS: Our bioinformatics analysis determined 11 key mRNAs, 9 hub miRNAs, and 18 lncRNAs which among them 2 coding RNA genes including DDIT4 and SULF1 as well as 3 non-coding RNA genes including TPTEP1, miR-181d-5p, and miR-148b-3p were selected for the further investigations. Expression of DDIT4, TPTEP1, and miR-181d-5p showed significantly increased levels while SULF1 and miR-148b-3p showed decreased levels in CRC tissues compared to the adjacent normal tissues. Positive relationships between DDIT4, SULF1, and TPTEP1 expression and metastasis and advanced stages of CRC were observed. Additionally, our results showed significant correlations between expression of TPTEP1 with DDIT4 and SULF1. CONCLUSIONS: Our findings demonstrated increased expression levels of DDIT4 and TPTEP1 in CRC were associated with more aggressive tumor behavior and more advanced stages of the disease. The positive correlations between TPTEP1 as non-coding RNA and both DDIT4 and SULF1 suggest a regulatory effect of TPTEP1 on these genes.

Expressions of TWIST1 and CD105 markers in colorectal cancer patients and their association with metastatic potential and prognosis.

BACKGROUND: TWIST1 and CD105, which contribute to tumor malignancy, are overexpressed in cancers. Accordingly, TWIST1 enhances epithelial-to-mesenchymal transition (EMT) and promotes the formation of cancer stem cells (CSCs). Also, CD105 is a neoangiogenesis marker in endothelial cells, which is introduced as a CSC marker in tumoral epithelial cells in several types of cancers. The present study was aimed to investigate expressions of TWIST1 and CD105 in colorectal cancer (CRC) patients. METHODS: Expressions of TWIST1 and CD105 in 250 CRC tissue samples were evaluated using immunohistochemistry on tissue microarrays (TMAs). In this regard, TWIST1 expression was investigated in the subcellular locations (cytoplasm and nucleus), while CD105 was mapped in endothelial cells and cytoplasmic tumor cells of CRC tissues. The association between the expression of these markers and clinicopathological parameters, as well as survival outcomes were analyzed. RESULTS: Results indicate a statistically significant association between higher nuclear expression levels of TWIST1 and distant metastases in CRC (P = 0.040) patients. In addition, it was shown that the increased nuclear expression of TWIST1 had a poor prognostic value for disease-specific survival (DSS) and progression-free survival (PFS) (P = 0.042, P = 0.043, respectively) in patients with CRC. Moreover, analysis of CD105 expression level has revealed that there is a statistically significant association between the increased expression of CD105 in tumoral epithelial cells and more advanced TNM stage (P = 0.050). CONCLUSIONS: Our results demonstrate that nuclear TWIST1 and cytoplasmic CD105 expressions in tumor cells had associations with more aggressive tumor behavior and more advanced diseases in CRC cases.

High expression of tumor susceptibility gene 101 (TSG101) is associated with more aggressive behavior in colorectal carcinoma.

INTRODUCTION: Identification of genetic determinants such as exosomal content that drives progression and metastasis of colorectal cancer (CRC) has received considerable attention. The present study aims to identify a suitable biomarker in CRC tissues and exosomes based on bioinformatics data to evaluate its expression patterns in CRC tissues as well as its clinicopathological significance. MATERIALS AND METHODS: Protein-protein interaction (PPI) network and enrichment analysis were applied to identify up-regulated genes that contributed in CRC exosomes to select the marker. The expression patterns and clinical significance of selected exosomal marker were evaluated in tissue microarrays (TMAs) of 445 CRC tumors and 39 adjacent normal tissues using immunohistochemistry method. RESULTS: Based on bioinformatics data, TSG101 gene was prominent amongst the tumor tissues and exosomes. Expression of TSG101 was significantly up-regulated in tumor cells compared to adjacent normal tissues (p-value = 0.04). Moreover, higher expressions of TSG101 (cytoplasmic and nuclear) were significantly associated with tumor differentiation (p-value = 0.042) and distant metastasis (p-value = 0.027). A significant association was found in the cytoplasmic expression of TSG101 between well and moderate tumor differentiation (p-value = 0.005) as well as moderate and poor differentiation (p-value = 0.050). CONCLUSION: These findings indicate that the exploration of crosstalk between exosome content and CRC may be valuable for the development of novel exosomal biomarkers. Increased expression of TSG101, as a promising exosome marker, is more associated with more aggressive tumor behaviors, metastasis, and progression of CRC, which paves the way for therapeutic strategies and CRC management. However, further investigations are warranted to clarify the molecular mechanisms of TSG101 in CRC.

The epigenetic alterations of human sperm cells caused by heroin use disorder.

The molecular mechanisms of drug use on sexual health are largely unknown. We investigated, the relationship between heroin use disorder and epigenetic factors influencing histone acetylation in sperm cells. The volunteers included twenty-four 20- to 50-year-old men with a normal spermogram who did not consume any drugs and twenty-four age- to BMI-matched men who consume only the drug heroin for more than last four months. HDAC1 and HDAC11 mRNA expression levels in spermatozoa and miR-34c-5p and miR-125b-5p expression levels in seminal plasma were measured. The heroin-user group showed significantly increased white blood cell counts and decreased sperm motility and survival rates (8.61 ± 1.73, 21.50 ± 3.11, 69.90 ± 4.69 respectively) as compared to the control group (1.49 ± 0.32, 38.82 ± 3.05, 87.50 ± 0.99 respectively) (p ≤ .001). An increase in DNA fragmentation index (DFI) (heroin-user group: 41.93 ± 6.59% and control group: 10.14 ± 1.43%, p = .003), a change in frequency of HDAC1 (heroin-user group: 1.69 ± 0.55 and control group: 0.45 ± 0.14, p = .045) and HDAC11 (heroin-user group: 0.29 ± 0.13 and control group: 2.36 ± 0.76, p = .019) in spermatozoa and a significant decrease in seminal miR-125b-5p abundance (heroin-user group: 0.37 ± 0.11 and control group: 1.59 ± 0.47, p = .028) were reported in heroin consumers. Heroin use can lead to male infertility by causing leukocytospermia, asthenozoospermia, DFI elevation in sperm cells and alterations in seminal RNA profile.

Low expression of Talin1 is associated with advanced pathological features in colorectal cancer patients.

To explore the proper prognostic markers for the likelihood of metastasis in CRC patients. Seventy-seven fresh CRC samples were collected to evaluate the mRNA level of the selected marker using Real-time PCR. Moreover, 648 formalin-fixed paraffin-embedded CRC tissues were gathered to evaluate protein expression by immunohistochemistry (IHC) on tissue microarrays. The results of Real-Time PCR showed that low expression of Talin1 was significantly associated with advanced TNM stage (p = 0.034) as well as gender (p = 0.029) in mRNA levels. Similarly, IHC results indicated that a low level of cytoplasmic expression of Talin1 was significantly associated with advanced TNM stage (p = 0.028) as well as gender (p = 0.009) in CRC patients. Moreover, decreased expression of cytoplasmic Talin1 protein was found to be a significant predictor of worse disease-specific survival (DSS) (p = 0.011) in the univariate analysis. In addition, a significant difference was achieved (p = 0.039) in 5-year survival rates of DSS: 65% for low, 72% for moderate, and 88% for high Talin1 protein expression. Observations showed that lower expression of Talin1 at both the gene and protein level may drive the disparity of CRC patients' outcomes via worse DSS and provide new insights into the development of progression indicators because of its correlation with increased tumor aggressiveness.

Dynamic Signature of tRNA-Derived Small RNAs in Cancer Pathogenesis as a Promising Valuable Approach.

AIM: Noncoding RNAs are a cluster of RNAs that do not encode functional proteins. Instead, they are incorporated into DNA structure and regulate gene expression. Of these two classes, transfer RNAs (tRNAs) belong to the former, and small RNAs (sRNAs) belong to the latter. Recently, tRNA-derived small RNAs (tsRNAs/tDRs) were discovered among small noncoding RNAs, as the newly discovered regulatory small RNA. They play a role in pathological and physiological processes, in which gene expression is frequently dysregulated. TsRNAs can be bound to Argonaute proteins and Piwi proteins, such as miRNAs and piRNAs sequentially. METHODS: In initial searches, 2,744 articles were identified with the following literature databases, up to February 25, 2020: PubMed, Embase, Web of Science, Scopus, and Google Scholar. Finally, after full-text assessment, 48 articles were identified that are related to gene expression profiling of tsRNA in cancer. RESULTS: The development of cancer biomarkers based on noncoding RNAs is a thriving area of biomedical research that has expanded significantly. Currently, several groups of tsRNA/tDR biomarkers should be considered in updating the latest findings. CONCLUSION: In this systematic review, we summarized the most recent findings related to the expression of tsRNAs in 17 cancer types. We suggested that use of tsRNAs in the cancer field attracted researcher focus and facilitated diagnostic and therapeutic approaches.

Enrichment of Up-regulated and Down-regulated Gene Clusters Using Gene Ontology, miRNAs and lncRNAs in Colorectal Cancer.

AIM AND OBJECTIVE: It is interesting to find the gene signatures of cancer stages based on the omics data. The aim of study was to evaluate and to enrich the array data using gene ontology and ncRNA databases in colorectal cancer. METHODS: The human colorectal cancer data were obtained from the GEO databank. The downregulated and up-regulated genes were identified after scoring, weighing and merging of the gene data. The clusters with high-score edges were determined from gene networks. The miRNAs related to the gene clusters were identified and enriched. Furthermore, the long non-coding RNA (lncRNA) networks were predicted with a central core for miRNAs. RESULTS: Based on cluster enrichment, genes related to peptide receptor activity (1.26E-08), LBD domain binding (3.71E-07), rRNA processing (2.61E-34), chemokine (4.58E-19), peptide receptor (1.16E-19) and ECM organization (3.82E-16) were found. Furthermore, the clusters related to the non-coding RNAs, including hsa-miR-27b-5p, hsa-miR-155-5p, hsa-miR-125b-5p, hsa-miR-21-5p, hsa-miR-30e-5p, hsa-miR-588, hsa-miR-29-3p, LINC01234, LINC01029, LINC00917, LINC00668 and CASC11 were found. CONCLUSION: The comprehensive bioinformatics analyses provided the gene networks related to some non-coding RNAs that might help in understanding the molecular mechanisms in CRC.

Common molecular markers between circulating tumor cells and blood exosomes in colorectal cancer: a systematic and analytical review.

Nearly half of patients with colorectal cancer (CRC), the third leading cause of cancer deaths worldwide, are diagnosed in the late stages of the disease. Appropriate treatment is not applied in a timely manner and nearly 90% of the patients who experience metastasis ultimately die. Timely detection of CRC can increase the five-year survival rate of patients. Existing histopathological and molecular classifications are insufficient for prediction of metastasis, which limits approaches to treatment. Detection of reliable cancer-related biomarkers can improve early diagnosis, prognosis, and treatment response prediction and recurrence risk. Circulating tumor cells (CTCs) and exosomes in peripheral blood can be used in a liquid biopsy to assess the status of a tumor. Exosomes are abundant and available in all fluids of the body, have a high half-life and are released by most cells. Tumor-derived exosomes are released from primary tumors or CTCs with selective cargo that represents the overall tumor. The current systematic review highlights new trends and approaches in the detection of CRC biomarkers to determine tumor signatures using CTC and exosomes. When these are combined, they could be used to guide molecular pathology and can revolutionize detection tools. Relevant observational studies published until July 24, 2019 which evaluated the expression of tumor markers in CTCs and exosomes were searched in PubMed, Scopus, Embase, and ISI Web of Science databases. The extracted biomarkers were analyzed using String and EnrichR tools.