Prediction of novel biomarkers for gastric intestinal metaplasia and gastric adenocarcinoma using bioinformatics analysis.

Background & aim: The histologic and molecular changes from intestinal metaplasia (IM) to gastric cancer (GC) have not been fully characterized. The present study sought to identify potential alterations in signaling pathways in IM and GC to predict disease progression; these alterations can be considered therapeutic targets. Materials & methods: Seven gene expression profiles were selected from the GEO database. Discriminate differentially expressed genes (DEGs) were analyzed by EnrichR. The STRING database, Cytoscape, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, NetworkAnalyst, MirWalk database, OncomiR, and bipartite miRNA‒mRNA correlation network was used for downstream analyses of selected module genes. Results: Analyses revealed that extracellular matrix-receptor interactions (ITGB1, COL1A1, COL1A2, COL4A1, FN1, COL6A3, and THBS2) in GC and PPAR signaling pathway interactions (FABP1, APOC3, APOA1, HMGCS2, and PPARA and PCK1) in IM may play key roles in both the carcinogenesis and progression of underlying GC from intestinal metaplasia. IM enrichment indicated that this is closely related to digestion and absorption. The TF-hub gene regulatory network revealed that AR, TCF4, SALL4, and ESR1 were more important for hub gene expression. It was revealed that the development and prediction of GC may be affected by hsa-miR-29. It was found that PTGR1, C1orf115, CRYL1, ALDOB, and SULT1B1 were downregulated in GC and upregulated in IM. Therefore, they might have tumor suppressor activity in GC progression. Conclusion: New potential biomarkers and pathways involved in GC and IM were identified that are important for the transformation of GC from IM to adenocarcinoma and can be therapeutic targets for GC.

Is there any difference between Eastern and Western clinical practice guidelines in management of gastric cancer?

BACKGROUND AND RECENT FINDINGS: Gastric cancer (GC) has been known as one of the most common causes of cancer mortality both in Western and Eastern countries. However, there might be differences between how it is managed in different countries. Thus, we aimed to investigate these differences. MATERIALS AND METHODS: The most well-known clinical guidelines in field of GC management including Korean GC Association (KGCA), Japanese GC Association (JGCA), National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO), British Society of Gastroenterology (BSG), and National Institute for health and Care Excellence (NICE) have been reviewed. RESULTS: The contents of these guidelines were categorized under eight headings including (1) genetic predisposition, (2) prevention, (3) management of gastric polyp, atrophy, dysplasia and metaplasia, (4) diagnosis, (5) pathology and molecular biology, (6) treatment, (7) supportive and palliative care, and (8) follow up. Difference in each section was discussed. CONCLUSION: Considering KGCA and JGCA as Eastern and NCCN, ESMO, BSG, and NICE as Western guidelines, it is revealed that both sets of guidelines share common practices such as prioritizing comprehensive diagnostic evaluations, personalizing treatment plans, and palliative care. However, main differences can be seen in treatment regimens, the adoption of newer therapies like immunotherapy, and the utilization of emerging techniques such as HIPEC. These differences reflect the diverse clinical landscapes, research focuses, and healthcare systems within these regions.

Thoracic duct identification with indocyanine green fluorescence to prevent chyle leaks during minimally invasive esophagectomy.

INTRODUCTION: Chylothorax (CT) is a rare yet serious complication after esophagectomy. Identification of the thoracic duct (TD) during esophagectomy is challenging due to its anatomical variation. Real-time identification of TD may help to prevent its injury. Near infra-red imaging with Indocyanine green (ICG) is a novel technique that recently has been used to overcome this issue. METHODS: Patients who underwent minimally invasive esophagectomy for esophageal cancer were divided into two groups with and without ICG. We injected ICG into bilateral superficial inguinal lymph nodes. Identification of TD and its injuries during the operation was evaluated and compared with the non-ICG group. RESULTS: Eighteen patients received ICG, and 18 patients underwent surgery without ICG. Each group had one (5.5%) TD ligation. In the ICG group injury was detected intraoperative, and ligation was done at the site of injury. In all cases, the entire thoracic course of TD was visualized intraoperatively after a mean time of 81.39 min from ICG injection to visualization. The Mean extra time for ICG injection was 11.94 min. In the ICG group, no patient suffered from CT. One patient in the non-ICG group developed CT after surgery that was managed conservatively. According to Fisher's exact test, there was no significant association between CT development and ICG use, possibly due to the small sample size. CONCLUSIONS: This study confirms that ICG administration into bilateral superficial inguinal lymph nodes can highlight the TD and reduce its damage during esophagectomy. It can be a standard method for the prevention of postoperative CT.

Expression and Clinical Significance of IRE1-XBP1s, p62, and Caspase-3 in Colorectal Cancer Patients.

Background: Three main cell signaling pathways including the endoplasmic reticulum stress (ERS) response, autophagy, and apoptosis play critical roles in both cell survival and death. They were found to crosstalk with one another during tumorigenesis and cancer progression. This study aimed to investigate the expression of the spliced form of X-box binding protein 1 (XBP1s), p62, and caspase-3, as the essential biomarkers of ERS, autophagy, and apoptosis in patients with colorectal cancer (CRC), as well as the correlation between their expression and clinicopathological data. Methods: This retrospective study was conducted on formalin-fixed paraffin-embedded (FFPE) blocks, which were collected from patients and their tumor margins, from the tumor bank of Imam Khomeini Hospital (Tehran, Iran) from 2017 to 2019. Tissue microarray (TMA) was used to measure the XBP1s, p62, and caspase-3 biomarkers. Data were analyzed using SPSS software version 20, and P≤0.05 was considered statistically significant. Results: Evaluating the total of 91 patients, a significant relationship was found between XBP1s expression and TNM stage (P=0.003), primary tumor (pT) (P=0.054), and the degree of differentiation (P=0.006); and between caspase-3 with pT (P=0.004), and lymphovascular invasion (P=0.02). However, no significant correlation was found between p62 and clinicopathological data. Furthermore, a positive relationship between XBP1s and p62 was confirmed (correlation coefficient: 22.2% and P=0.05). Conclusion: Our findings indicated that XBP1s could be considered as a target for therapy in personalized medicine.

Investigation of Molecular Mechanisms of S-1, Docetaxel and Cisplatin in Gastric Cancer with a History of Helicobacter Pylori Infection.

Gastric cancer rates and fatality rates have not decreased. Gastric cancer treatment has historically included surgery (both endoscopic and open), chemotherapy, targeted therapy, and immunotherapy. One of the aggravating carriers of this cancer is Helicobacter pylori infection. Various drug combinations are used to treat gastric cancer. However, examining the molecular function of these drugs, depending on whether or not there is a history of Helicobacter pylori infection, can be a better help in the treatment of these patients. This study was designed as bioinformatics. Various datasets such as patients with gastric cancer, with and without a history of H. pylori, and chemotherapy drugs cisplatin, docetaxel, and S-1 were selected. Using Venn diagrams, the similarities between gene expression profiles were assessed and isolated. Then, selected the signal pathways, ontology of candidate genes and proteins. Then, in clinical databases, we confirmed the candidate genes and proteins. The association between gastric cancer patients with and without a history of H. pylori with chemotherapy drugs was investigated. The pathways of cellular aging, apoptosis, MAPK, and TGFß were clearly seen. After a closer look at the ontology of genes and the relationship between proteins, we nominated important biomolecules. Accordingly, NCOR1, KIT, MITF, ESF1, ARNT2, TCF7L2, and KRR1 proteins showed an important role in these connections. Finally, NCOR1, KIT, KRR1, and ESF1 proteins showed a more prominent role in the molecular mechanisms of S-1, Docetaxel, and Cisplatin in gastric cancer associated with or without H. pylori.

The integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancer.

Circular RNAs (circRNA) are known to function as competing endogenous RNA (ceRNA) in various cancers by regulating microRNAs (miRNA). However, in colorectal cancer (CRC), the precise pathological role of circ000240/miRNA/mRNA remains indeterminate. The expression level of hsa_circ_000240 was evaluated using qRT-PCR in matching pairs of CRC tumor and adjacent normal tissue samples in our laboratory. Then, to determine whether hsa_circ_000240 acted as a ceRNA in CRC, the linked miRNAs and gene targets were retrieved. Topological analysis of candidate genes using a network approach identified the most critical hub genes and subnetworks related to CRC disease. Microarray and bulk RNA sequencing analyses were utilized to comprehensively evaluate the expression levels of both miRNA and mRNA in CRC. Single-cell RNA-seq analysis was also used to evaluate the significant overall survival (OS) genes at the cellular level. ATAC-seq data provided insights into candidate genes' accessible chromatin regions. The research uncovered a considerable upregulation of hsa_circ_000240 in CRC tissues. Three miRNAs interacted with the target circRNA. One thousand six hundred eighty intersected genes regulated by three miRNAs were further identified, and the relevant functionality of identified neighbor genes highlighted their relevance to cancer. The topological analysis of the constructed network has identified 33 hub genes with notably high expression in CRC. Among these genes, eight, including CHEK1, CDC6, FANCI, GINS2, MAD2L1, ORC1, RACGAP1, and SMC4, have demonstrated a significant impact on overall survival. The utilization of single-cell RNA sequencing unequivocally corroborated the augmented expression levels of CDC6 and ORC1 in individuals with CRC, alongside their noteworthy connection with the infiltration of immune cells. ATAC-seq analyses revealed altered accessibility regions in Chr2, 4, and 12 for CDC6 and ORC1 high-expression. Correlation analysis of CDC6 and ORC1 further highlighted the association of candidate gene expression with exhaustion markers such as CTLA4, CD247, TIGIT, and CD244. The candidate genes exhibit a positive correlation with chromatin remodeling and histone acetylation. These epigenetic modifications play a significant role in influencing the cancer progression following expression of CDC6 and ORC1 in CRC. Additionally, results showed that the methylation rate of the promoter region of CDC6 was elevated in CRC disease, confirming the functional importance of CDC6 and their interaction with hsa_circ_000240 and associated ceRNA in CRC. In conclusion, this study highlights hsa_circ_000240's role as a ceRNA in CRC. It opens new avenues for further dissection of CDC6, ORC1, and underlying novel epigenetics and immunotherapy targets for CRC therapy.

Single-Cell Transcriptomics for Unlocking Personalized Cancer Immunotherapy: Toward Targeting the Origin of Tumor Development Immunogenicity.

Cancer immunotherapy is a promising approach for treating malignancies through the activation of anti-tumor immunity. However, the effectiveness and safety of immunotherapy can be limited by tumor complexity and heterogeneity, caused by the diverse molecular and cellular features of tumors and their microenvironments. Undifferentiated tumor cell niches, which we refer to as the "Origin of Tumor Development" (OTD) cellular population, are believed to be the source of these variations and cellular heterogeneity. From our perspective, the existence of distinct features within the OTD is expected to play a significant role in shaping the unique tumor characteristics observed in each patient. Single-cell transcriptomics is a high-resolution and high-throughput technique that provides insights into the genetic signatures of individual tumor cells, revealing mechanisms of tumor development, progression, and immune evasion. In this review, we explain how single-cell transcriptomics can be used to develop personalized cancer immunotherapy by identifying potential biomarkers and targets specific to each patient, such as immune checkpoint and tumor-infiltrating lymphocyte function, for targeting the OTD. Furthermore, in addition to offering a possible workflow, we discuss the future directions of, and perspectives on, single-cell transcriptomics, such as the development of powerful analytical tools and databases, that will aid in unlocking personalized cancer immunotherapy through the targeting of the patient's cellular OTD.

Application of Breast Scintigraphy for Patients with Suspicious (Breast Imaging-Reporting and Data System IV) Breast Lesions.

Background: The surgery for a breast imaging-reporting and data system (BIRADS) IV lesions needs imaging or pathology supporting data. The roll of breast scintigraphy for this purpose is unclear. Materials and Methods: In a prospective design, 16 patients with 25 BIRADS IV lesions who were scheduled for surgery were included. Before the surgery, breast scintigraphy was done using a nondedicated dual head gamma camera in the prone position employing a shaped foam pad providing imaging at breast pendulous position. Twenty mCi99m Tc methoxy-isobutyl-isonitrile was injected and two 15 and 60-min delayed imaging were done (anterior, bilateral, and single photon emission computed tomography [SPECT] projections). Pathology reports were collected and tumor to nontumor uptake ratio (T/NT) was analyzed, accordingly. Results: Out of all lesions, 12 were malignant (invasive ductal and lobular carcinoma ductal carcinoma in situ). At 15 min, T/NT was insignificantly higher in the malignant compared to benign lesions (22.8 ± 23.9 vs. 10.1 ± 10.1; P = 0.109). The optimal T/NT cutoff for discrimination of malignant and benign lesions was 20. Only 1 out of 13 benign lesions presented uptake >20 (7.7%; false-positive rate; P = 0.047). The diagnostic accuracy, sensitivity, and specificity for T/NT calculated at 0.68, 0.42, and 0.92, respectively. The T/NT at 60 min remained unchanged for either benign or malignant lesions (22.3 ± 30.2 vs. 11.7 ± 17.1; P = 0.296). Conclusions: Breast scintigraphy with general purpose gamma camera employing SPECT imaging may assist the selection of BIRADS IV lesions in need for surgery. All uptake positive cases should undergo surgery and decision for uptake negative cases should be made based on other data.

Risk of secondary tumours in patients with non-metastatic and metastatic human retinoblastoma.

BACKGROUND: Retinoblastoma is an intraocular cancer in children and infants. Despite all the available treatment options and high survival rates in children with retinoblastoma, exposure to secondary tumours in adulthood is one of the concerns that physicians face. In many cases, dysfunction of the RB1 gene is the main cause of secondary tumours due to retinoblastoma. Therefore, the aim of this study was to evaluate the incidence of other secondary tumours in children with retinoblastoma. METHODS: In this regard, we performed continuous and integrated bioinformatics analyses to find genes, protein products, and signal pathways involved in other cancers. RESULTS: 1170 high-expression genes and 960 low-expression genes between non-invasive and invasive retinoblastoma were isolated. After examining the signal pathways, we observed bladder cancer and small cell lung cancer in the overexpressed genes. We also observed 5 cancers of endometriosis, prostate, non-small cell lung cancer, glioblastoma and renal cell carcinoma in low-expression genes. Based on the P-value index, non-small cell lung cancer, prostate and bladder cancers had the highest risk, and endometriosis cancer showed a lower probability of developing a secondary tumour in patients with retinoblastoma. In addition, the network between proteins also showed us that TP53, CDK2, SRC, MAPK1 proteins with high expression and JUN, HSP90AA1, and UBC proteins with low-expression play a significant role in candidate cancers. CONCLUSION: Lastly, we used continuous bioinformatics analysis to show that seven cancers are strongly linked to retinoblastoma cancer. Of course, more research is needed to find the best way to care for children who have been treated for retinoblastoma.

A Panel of Circulating microRNAs as a Potential Biomarker for the Early Detection of Gastric Cancer.

Background: The high mortality rate of Gastric Cancer (GC) is a consequence of delayed diagnosis. The early diagnosis of GC could increase the five-year survival rate among patients. We aimed to find a panel of microRNAs (miRNA) for the detection of GC in the early stages. Methods: In this case-control study, we selected consistently upregulated miRNAs from the results of 12 high-throughput miRNA profiling studies in GC. In the profiling phase, the differential expressions of 13 candidate miRNAs were analyzed by quantitative reverse-transcription PCR (qRT-PCR) in two pooled RNA samples prepared from the plasma of eight GC patients and eight matched controls. In the validation phase, significantly upregulated miRNAs from the profiling phase were further evaluated in the plasma samples of 97 patients with stage I-IV gastric adenocarcinoma and 100 healthy controls. Results: In the profiling phase, six miRNAs (miR-18a, 21, 25, 92a, 125b and 221) were significantly upregulated in the GC patients compared to the controls (p<0.05). However, in the validation phase, only significant up-regulation of miR-18a, 21 and 125b was confirmed (p<0.05). A panel of miR-18a/21/125b was able to detect GC patients with stage I-IV from the controls (p<0.001; AUC=0.92, sensitivity=86%; specificity=85%). In addition, the panel could distinguish the early-stage GC (I+II) from the control group with an AUC of 0.83, a sensitivity of 83%, and a specificity of 75%. Conclusion: A panel of circulating miR18a/21/125b could be suggested as a potential biomarker for the early detection of GC.

Investigation of key signaling pathways and appropriate diagnostic biomarkers selection between non-invasive to invasive stages in pancreatic cancer: a computational observation.

Pancreatic cancer is the seventh most lethal cancer in the world. Despite its moderate prevalence, the 5-year survival rate of patients with pancreatic cancer is about 10%. Despite different therapeutic and diagnostic strategies for pancreatic cancer, this cancer is still uncontrollable in the invasive stage and can invade various body organs and cause death. Early detection for pancreatic cancer can be an excellent solution to manage treatment better and increase patients' survival rates. This study aimed to find diagnostic biomarkers between non-invasive to invasive stages of pancreatic cancer in the extracellular matrix to facilitate the early diagnosis of this cancer. Using bioinformatics analysis, we selected the appropriate datasets between non-invasive and invasive pancreatic cancer stages and categorized their genes. Then, we charted and confirmed the signaling pathways, gene ontology, protein relationships, and protein expression levels in the human samples using bioinformatics databases. Cell adhesion and hypoxia signaling pathways were observed in up-regulated genes, different phases of the cell cycle, and metabolic signaling pathways with down-regulated genes between non-invasive and invasive pancreatic cancer stages. For proper diagnostic biomarkers selection, the overexpressed genes that released protein into the extracellular matrix were examined in more detail, with 62 proteins selected and SPARC, THBS2, COL11A1, COL1A1, COL1A2, COL3A1, SERPINH1, PLAU proteins chosen. Bioinformatics analysis can more accurately assess the relationship between molecular mechanisms and key actors in pancreatic cancer invasion and metastasis to facilitate early detection and improve treatment management for patients with pancreatic cancer.

Transhiatal versus transthoracic esophagectomy for esophageal SCC: outcomes and complications.

BACKGROUND: Transhiatal esophagectomy (THE) and transthoracic esophagectomy (TTE) are both accepted procedures for esophageal cancer but still the most effective surgical approach continues to be controversial. This study aimed to determine post-operative complications and outcomes of TTE compared with THE. METHODS: A retrospective analysis was performed on data of 243 adult patients with resectable esophageal cancer who underwent THE or TTE between December 2016 and October 2018. Demographic data, consisting of preoperative co-morbidities, disease stage, and perioperative morbidity and mortality were collected. RESULTS: Among the patients, 99 individuals (40.7%) had a transhiatal resection and 144 (59.3%) had a transthoracic resection. Most patients (83.1%) were above 50 years old with no significant difference between groups (p = 0.297). The frequency distribution of comorbidities was similar in both groups. The most common site of the tumor in TTE group was middle esophagus and in THE group was lower esophagus. The most common complication was recurrence of dysphagia which was more common in THE group without significant difference. The other complications including pulmonary and cardiac events, tracheal and recurrent laryngeal nerve injury, chylothorax and anastomosis stricture did not differ between the groups. The operative mortality within 30 days after the operation was 2.8% with significant difference favored the THE group (THE 0%, TTE 5.2%, p = 0.033). CONCLUSION: Because of the controversies, the decision on the type of surgical technique in esophageal cancer treatment hinges on patient's co-morbidities, cancer stage, tumor location and surgeon's experience.

A solitary precaval right renal artery: A case report.

Knowledge of aberrant renal vasculature is critical for preoperative planning of either open or minimally invasive renal surgery. A precaval right renal artery is a rare anatomical variant in which the artery passes anterior to the inferior vena cava(IVC), as opposed to coursing posteriorly. When encountered, this artery is mostly accessory and thus accompanied by renal vessels in orthotopic position. Here, we describe an unusual instance of a solitary, main precaval right renal artery. It can be diagnosed preoperatively by a cross-sectional imaging study. Awareness of this anomaly is very important to prevent iatrogenic injury during surgical intervention.

Fever of unknown origin as the first presentation of candida vertebral osteomyelitis: A case report.

Candida osteomyelitis is a rare disorder; however, its incidence has drastically risen especially during the last 3 decades. Diagnosis is usually delayed due to nonspecific symptoms. Thus, its management would not be performed at the proper time, which leads to increased morbidity. The optimal management of candida osteomyelitis is not clearly defined but most recommendations advise prolonged antifungal therapy in addition to surgery. Here, we report candida osteomyelitis in a patient with a history of pancreatic adenocarcinoma that presented with prolonged FUO as her first presentation. Fortunately, her symptoms completely resolved after prolonged medical therapy despite delay diagnosis due to her unusual presentation. To the best of our knowledge, it is the first report of candida vertebra osteomyelitis that presents with prolonged FUO as the first presentation.

The potential of PIK3CA, KRAS, BRAF, and APC hotspot mutations as a non-invasive detection method for colorectal cancer.

BACKGROUND: Early diagnosis of colorectal cancer (CRC) can lead to prompt treatment modalities. Circulating cell-free DNA (cfDNA) analysis provides an alternative non-invasive procedure for the study of the molecular profiles of the corresponding tumor tissue. In this study, we aimed to investigate PIK3CA, KRAS, BRAF, and APC hotspot mutations in CRC tumor tissue, besides evaluating the diagnostic performance of KRAS, BRAF, and PIK3CA mutations in the plasma cfDNA. METHOD: Primary CRC tissue samples and paired plasma samples were collected from 70 patients. After DNA extraction, PCR-direct sequencing was used to screen for mutations in PIK3CA exon 9 and APC exon 15 in tumor tissues. Amplification Refractory Mutation System (ARMS)-quantitative PCR (qPCR) was used to evaluate KRAS codon 12 and 13, BRAF V600E, and PIK3CA exon 9 hotspot mutations. RESULTS: PIK3CA exon 9 hotspot mutations were detected in 47.1% of tumor tissues and 20% of paired plasma cfDNA samples by ARMS-qPCR method, while Sanger sequencing did not identify any mutation in PIK3CA exon 9. The KRAS exon 2 mutations were detected in 71.4% and 34.3% of tumor tissue samples and paired plasma cfDNA respectively. BRAF V600E mutation was observed in 17.1% and 4.3% of tissue DNA and plasma cfDNA respectively. A panel of PIK3CA, KRAS, and BRAF showed a sensitivity of 61% and a specificity of 100% (AUC = 0.803). APC hotspot mutations were observed in 76.8% of CRC tissue samples. APC mutations were not analyzed in the plasma samples. The co-existence of KRAS/PIK3CA/APC gene mutations encompassed the highest frequency among all combinations of mutations. BRAF and PIK3CA mutations were significantly more frequent in older patients. CONCLUSION: We demonstrated that a panel consisting of PIK3CA, KRAS, and BRAF mutations showed good diagnostic performance for detecting CRC in the plasma cfDNA.

Clinicopathologic significance of DNA replication licensing factors in head and neck diffuse large B-cell lymphoma.

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) harbors defects in the proliferation pathway. We performed multiparameter analysis of proteins expressed during different cell cycle phases and correlated them with clinical parameters of head and neck DLBCLs. STUDY DESIGN: Thirty-nine DLBCLs were staged and immunohistochemically stained with MCM2, Ki67, and geminin. The receiver operating characteristic curve and its area under the curve were calculated, and sensitivity vs specificity curve analysis was performed. RESULTS: The highest labeling index was in MCM2, followed by Ki67 and geminin (P < .001). All pairs showed significant differences (P < .001). The best cutoff points to differentiate limited from advanced disease were 68% and 45% for MCM2 and Ki67, respectively. There was no acceptable cutoff for geminin (area under the curve = 0.667, P = .134). MCM2/Ki67 (P = .293) and geminin/Ki67 (P = .233) ratios did not differ between the stages. The median (interquartile range) of the geminin/Ki67 ratio was 0.57 (0.68), translating to a reduced G1. CONCLUSIONS: We suggest a role for cell cycle-related proteins in the biology and behavior of DLBCLs. MCM2 and Ki67 cutoffs can be a potential option to differentiate limited from advanced disease, where imaging and laboratory techniques are unavailable. The G1 decrease and the significantly higher MCM2 expression compared to Ki67 indicate replication disturbances, making factors involved in the G1 phase targets for treatment.

Methylation of FBN1, SPG20, ITF2, RUNX3, SNCA, MLH1, and SEPT9 genes in circulating cell-free DNA as biomarkers of colorectal cancer.

BACKGROUND: Investigating aberrant tumor-specific methylation in plasma cell-free DNA provides a promising and noninvasive biomarker for cancer detection. OBJECTIVE: We aimed to investigate methylation status of some promoter regions in the plasma and tumor tissues to find biomarkers for early detection of colorectal cancer. METHODS: This case-control study on seventy colorectal cancer patients and fifty matched healthy controls used Methylation-Specific High-Resolution Melting Curve analysis to evaluate the methylation of the selected promoter regions in converted genomic tissue DNA and plasma cfDNA. RESULTS: The methylation levels in selected regions of SPG20 (+24375 to +24680, +24209 to +24399, and +23625 to +23883), SNCA (+807 to +1013, +7 to +162, and -180 to +7), FBN1 (+223 to +429, +1 to +245, and -18 to -175), ITF2 (+296 to +436 and -180 to +55), SEPT9 (-914412 to -91590 and -99083 to -92264), and MLH1 (-13 to +22) were significantly higher in tumor tissues compared with normal adjacent tissues. The methylation levels of FBN1, ITF2, SNCA, and SPG20 promoters were significantly higher in the patient's plasma compared to patient's normal tissue and plasma of healthy control subjects. FBN1, SPG20, and SEPT9 promoter methylation had a good diagnostic performance for discriminating CRC tissues from normal adjacent tissues (AUC > 0.8). A panel of SPG20, FBN1, and SEPT9 methylation had a higher diagnostic value than that of any single biomarker and other panels in tissue-based assay (AUC > 0.9). The methylation of FBN1(a) and SPG20(a) regions, as the closest region to the first coding sequence (CDS), had a good diagnostic performance in plasma cfDNA (AUC > 0.8) while a panel consisted of FBN1(a) and SPG20(a) regions showed excellent diagnostic performance for CRC detection in plasma cfDNA (AUC > 0.9). CONCLUSION: Methylation of FBN1(a) and SPG20(a) promoter regions in the plasma cfDNA can be an excellent simple, non-invasive blood-based test for early detection of CRC.

Dysregulated Expression of miR-146a and Its Associated Immune Effectors in Peripheral Blood Mononuclear Cells of Esophageal Carcinoma Patients.

Esophageal cancer is one of the least studied aggressive tumors, with the squamous cell carcinoma (ESCC) being the most frequent histological type around the world. Growing evidence has shown that the abnormal expression of microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) is closely related to the pathogenesis of cancers. MiR-146a is a crucial regulator of inflammatory cascades. There is currently no data available regarding the possible role of miR-146a in PBMCs of ESCC patients. We evaluated the expression of miR-146a, as well as its target genes (IRAK1 and TRAF6) and its associated immune effectors (NF-κB1, IL1B, and IL6) in PBMCs of 40 ESCC patients and 50 control subjects. The geometric mean expression of five transcripts was used for normalizing expressions. The PBMC level of miR-146a, as measured by RT-qPCR, was upregulated, whereas levels of its target genes, IRAK1 and TRAF6, were downregulated in ESCC patients. NF-κB1 and IL6 was downregulated in PBMCs of ESCC patients. There was no difference in terms of the IL1B level between patients and the control group. Logistic regression and receiver operating characteristic curve analysis suggested that a model with PBMC levels of either NF-κB1+ IL6 or NF-κB1+ miR-146a as predictors may discriminate ESCC patients from subjects of the control group. Our findings, in the context of the current literature, may suggest a possible downregulatory mechanism of immune responses in PBMCs of ESCC patients.

The Expression Levels of Circulating miR-129 and miR-203a in Association with Breast Cancer and Related Metastasis.

Background: A significant part of deaths related to breast cancer is the result of invasion to other organs. It is essential to discover new non-invasive biomarkers to improve anticipation of recurrence risk in breast cancer patients. In this study, the plasma levels of miR-129 and miR-203a were evaluated to investigate their diagnostic potential in breast cancer and its metastasis. Methods: In this case-control study, conducted in Tarbiat Modares University, Tehran, Iran, in 2019, Invasive Ductal Carcinoma blood samples were divided into 3 groups based on their stages as I, II/III, IV. Each group contained 30 individuals. We also recruited 30 normal individuals as a control group. Real-Time PCR was conducted to evaluate miR-129 and miR-203a expression levels. The discriminatory ability of the evaluated plasma miRNAs was assessed by ROC (Receiver Operating Characteristic) curves in breast cancer diagnosis and its metastasis. Results: MiR-129 and miR-203a expression levels were significantly downregulated in breast cancer. Reducing tendency was observed in the mentioned miRNAs from less to more invasive stages. The expression level of miR-129 was decreased in metastatic than non-metastatic patients and it was significantly related to metastasis. A significant association between miR-129 expression level and lymph node status was also observed (P=0.04). Evaluation of ROC curves revealed that miR-129 and miR-203a were able to discriminate breast cancer fairly and poorly respectively. The ability of miR-129 in the diagnosis of breast cancer metastasis was poor. Conclusion: MiR-129 and miR-203a may both act as tumor suppressor miRNAs. Our results need further evidence in a large population to be confirmed as diagnostic markers.

Integrative and in-vitro analysis reveal hsa_circ_001787 can act as a diagnostic biomarker for colorectal cancer.

BACKGROUND: Circular RNAs (circRNAs) are a new kind of non-coding RNA(ncRNA). Throughout research, we see an increase in the number of studies demonstrating that circRNAs occupy a pivotal role in the growth and advancement of human tumors. Nevertheless, hsa_circ_001787's role in the evolution of colorectal cancer (CRC) remains unclear. This current study ascertained the expression level of circRNA001787 in CRC specimens and neighboring healthy tissues, and investigated the miRNAs associate with hsa_circ_001787, as well as the relationship between hsa_circ_001787 and pathological factors. METHOD: First, the expression level of hsa_circ_001787 was measured in 43 matched Tissues from CRC and normal tissues through using real-time quantitative reverse transcription PCR (qRT-PCR). Second, based on circular RNA-microRNA and microRNA-mRNA pairs, a circRNA-miRNA-mRNA network was created. The survival rate of mRNAs was investigated through the GEPIA in the network. Regarding the elucidated function analysis of hsa_circ_001787, The biological, molecular, cellular function (GO) and pathway (KEGG) enrichment was obtained. RESULT: We detected that hsa_circ_001787 expression level was significantly down expressed in CRC tissue versus paired CRC histological normal tissue. The area under the curve (AUC) was 0.83. The expression level of hsa_circ_001787 was significantly associated with pathological factors such as tumor grade and the primary site of the tumor. Based on the hsa_circ_001787, a novel circRNA/miRNA/mRNA network has been built up, four miRNAs, and 24 mRNA. The pathway of mRNAs analyzed in the pathogenesis of CRC. Four genes distinguished via the GEPIA database were positively linked to the overall survival of CRC patients. CONCLUSION: Our study suggested that hsa_circ_001787 was significantly down-regulated in CRC. We might be able to use this as a new biomarker in the screening of CRC. Furthermore, our finding achieves a broader understanding of the regulatory mechanisms by which hsa_circ_001787 acts as ceRNA in colorectal cancer.