Development Of Colorectal Cancer Research Articles

Detection of JC and BK polyomaviruses in patients with colorectal cancer (CRC) by PCR

ABSTRACT Background Overall, 20–30% of all cancers are estimated to be linked to infectious agents. Polyomaviruses are oncogenic cause in rodent models, readily transform their cells, and cause chromosomal instability in animal and human cells in-vitro. Some reports have indicated the presence of JCPyV and BKPyV in some human tumors. The JCPyV and BKPyV genome encodes some transforming proteins such as LT-Ag. Thus, these viruses could cause or promote some neoplasia, such as lymphomas, pancreatic, prostate, and colorectal cancers. Colorectal cancer (CRC) is the third most common cancer in the world. Risk factors for developing CRC are associated with personal features or habits, such as age, lifestyle, and gut microbiota. Materials and Methods In this study, we examined the prevalence of JCPyV and BKPyV in the 23 fecal samples of CRC patients and 24 healthy samples (control group). Virus DNA was extracted by a Favorgen DNA extraction kit. The large T antigen of JCPyV and VP1 of BKPyV were investigated by optimized multiplex PCR. Results One of the samples was positive for the JCPyV (4.3%), while in the samples of healthy individuals, the JCPyV was negative. Also, positive results for BKPyV PCR were obtained for five cases (21.7%) in the samples of the CRC group and one case (4.1%) in healthy individuals. Conclusion The result showed no direct correlation between tumorigenesis and polyomavirus infections in CRC development. However, the exact role of BKPyV and JCPyV is still controversial and needs further study with larger sample size.

Exosomal CircRNAs: A Future Star in Colorectal Cancer.

Colorectal cancer (CRC) is currently the third most common malignancy world-wide, with an increasing mortality rate and treatment resistance. Due to the lack of effective biomarkers and therapeutic targets, the early diagnosis and treatment of colorectal cancer re-main suboptimal. Circular RNAs (circRNAs) are a novel class of non-coding RNAs with co-valent closed-loop structures that are well stabilized and conserved and are involved in multi-ple pathological conditions in humans. CircRNAs have been identified to be enriched and sta-ble in exosomes. In addition, there is growing proof that exosomal circRNAs that have been identified as oncogenes or tumor suppressors regulate CRC growth, migration, and sensitivity to radiotherapy and chemotherapy. Exosomal circRNAs represent promising candidates as di-agnostic biomarkers and anti-tumor targets. In this article, we explore recent studies on exo-somal circRNAs in CRC and describe their biological functions in colorectal cancer develop-ment, illustrating their potential as biomarkers and targeted therapeutic capabilities.

Cytochrome P450 F3 promotes colorectal cancer via inhibiting NRF2-mediated ferroptosis

Cytochrome P450 F3 (CYP4F3) is recognized as a disease-associated immune response initiator that is involved in the synthesis of cholesterol, steroids, and lipids. This study identified the upregulation of CYP4F3 expression in colorectal cancer (CRC) and its association with poor patient prognosis through a comparative analysis between CRC tumor tissues with normal tissues from public databases. The overexpression of CYP4F3 in CT26.wt and SW620, promoted cell proliferation and migration, a reduction of cellular oxidative stress, an up-regulation of the oxidative stress-related pathway NRF2, and an inhibition of cellular ferroptosis. Additionally, inhibition of NRF2 activity stimulated cellular ferroptosis when CYP4F3 was overexpressed. Ferroptosis, characterized by iron-dependent lipid peroxidation, is a non-apoptotic way of cell death with a critical role in cancer development. When given a ferroptosis agonist to CYP4F3-overexpression CRC cells, NRF2 was activated, and cell proliferation and migration were reduced. Furthermore, the mice subcutaneously injected with CYP4F3-overexpression CT26.wt cells formed significantly larger tumors compared to the CYP4F3-vector CT26.wt cell group. This study systematically identified an important role of CYP4F3 in CRC development as a regulator of CRC cells to escape ferroptosis via NRF2, highlighting the significance of CYP4F3 as a potential therapeutic target for CRC.

Triglyceride-Glucose Index, Modifiable Lifestyle, and Risk of Colorectal Cancer: A Prospective Analysis of the Korean Genome and Epidemiology Study.

Insulin-mediated pathways plausibly explain the pathogenesis of colorectal cancer (CRC). The triglyceride-glucose index (TyG) is a surrogate of insulin resistance (IR), but its association with CRC in the Korean population has not been evaluated. From the 2004-2013 Korean Genome and Epidemiology Study, 98,800 participants aged 40-69 years were followed through 2020. Data on CRC incidence were obtained from the Korean National Cancer Center registry. Cox regression models and restricted cubic splines were fitted to examine the association between the TyG; In [(triglycerides) × (fasting glucose)/2] and CRC incidence. Joint effects of modifiable lifestyle factors and TyG on CRC risk were also investigated. Median follow-up time was 10.6 years, and 699 CRC cases were observed. A unit-increment in TyG was associated with increased risk of CRC combined (hazard ratio, HR: 1.28, and 95% confidence interval, CI: 1.12-1.46), colon (1.29, 1.10-1.54), and rectal cancer (1.24, 1.01-1.52). Associations were dose-dependent, with linear associations observed for CRC and colon, but non-linear associations were observed for rectal cancer. A high TyG index (above 8.4) combined with overweight/obesity was linked to an increased risk of CRC (1.31, 1.07-1.61) and colon cancer (1.33, 1.03-1.72). When combined with low fruit and vegetable intake, the risks were higher for CRC (1.40, 1.12-1.74) and colon cancer (1.57, 1.18-2.09). Combined with high red meat consumption, the risks were elevated for CRC (1.32, 1.05-1.65) and colon cancer (1.52, 1.15-2.02). A high TyG index was associated with a higher risk of colorectal cancer, and the risk was highest among participants with a high BMI, low fruit and vegetable intake, and high intake of red meat, suggesting a role of both insulin resistance and modifiable lifestyle in colorectal cancer development.

Studies on the ameliorative potential of Rheum webbianum rhizome extracts on 1,2-dimethylhydrazine (DMH) induced colorectal cancer and associated hepatic and haematological abnormalities in swiss albino rats

Ethnopharmacological relevanceRheum webbianum Royle (RW) holds significant ethnopharmacological importance owing to its 5000-year history of cultivation for medicinal and culinary purposes. Demonstrating therapeutic advantages in traditional and contemporary medical practices, RW exhibits key pharmacological effects including anticancer activity, gastrointestinal control, anti-inflammatory properties, and suppression of fibrosis. Despite its recognized vast bioactivities in ethnopharmacology, its efficacy against the colorectal cancer (CRC) remains incompletely understood. Aim of the studyThis study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development. Materials and methodsFour types of RW extracts were prepared by using different solvents viz: Hexane, Ethy-acetate, Ethanol and Methanol. All the four extracts were evaluated for cytotoxicity on HCT-116 human CRC cells. Promising extracts were further investigated in-vivo at varying doses using 1,2-dimethylhydrazine (DMH) induced rat CRC model to assess the anti-oxidant and anticancer properties as well as their effects on the associated hepatic deterioration and hematological alterations. ResultsCell viability: In-vitro assessments demonstrated a dose and time-dependent reduction in HCT-116 cell viability following treatment with methanolic and ethanolic extracts of RW, reducing viability by up to 85% and 90%, respectively, at 200 μg/ml. Histopathology: Histopathological analyses revealed significant improvements in colon tissue morphology in RW extract-treated groups compared to DMH-only treated animals. RW-treated groups showed reduced structural abnormalities, congestion, inflammatory cell infiltration, crypt abscess formation, and dysplasia. In contrast, the DMH-only group exhibited irregular glandular structure, mucosal destruction, extensive inflammatory cell infiltration, crypt abscess formation, and dysplasia. These results highlight the potential of RW methanolic and ethanolic extracts in mitigating colon cancer-related histopathological alterations. Haematological, and hepatic parameters: In the DMH-induced colorectal cancer rat model, significant hematological imbalances were evident, including a 49.13% decrease in erythrocytes, 32.18% in hemoglobin, and 26.79% in hematocrit, along with a 79.62% increase in white blood cells and 68.96% rise in platelets. Administration of RW rhizome extracts effectively restored these hematological parameters to levels comparable to those in the control group. Furthermore, RW treatment significantly reduced serum ALT and AST levels, which had increased by 36.78% and 33.12%, respectively, due to DMH exposure. RW intervention also mitigated the onset of atherosclerosis, evidenced by notable reductions in serum total cholesterol and triglyceride levels. Comparative analysis indicated that RW-treated DMH groups effectively restored lipid profiles, contrasting with the DMH-only group which exhibited markers indicative of colon cancer. Oxidative stress: The DMH-treated group showed a significant increase in MDA levels by 195.59%, indicative of heightened free radical production, coupled with decreased levels of SOD (33%), CAT (48%), GSH (58%), and GR activity (49%), signifying oxidative stress. Treatment with RW extracts in DMH-treated rats markedly reduced MDA levels and enhanced SOD, CAT, GSH, and GR activities. These results underscore the antioxidant efficacy of RW extracts. ConclusionThis study underscores the significant potential of RW rhizome extracts in inhibiting colorectal cancer development. Further investigations are warranted to identify the active constituents responsible for these promising outcomes, positioning RW as a natural and potential agent in combating colon cancer.

Investigating the WNT and TGF-beta pathways alterations and tumor mutant burden in young-onset colorectal cancer

Colorectal cancer (CRC) is the third most common cancer in the United States. Recent epidemiological evidence demonstrates an increasing incidence of young-onset CRC cases, defined as CRC cases in individuals 50 years old or younger. Studies have established that alterations in both the WNT and TGF-Beta signaling pathways have contributed to CRC development. While this is well understood, the comprehensive analysis of WNT and TGF-Beta pathway alterations in young-onset CRC cases has yet to be investigated. Here, we conducted a comprehensive bioinformatics analysis of mutations associated with each of the WNT and TGF-Beta signaling pathways according to age (≤ 50 years old versus > 50 years old) utilizing published genomic data from the cBioPortal. Chi-square results demonstrated no significant difference in WNT alterations between young-onset CRC and those > 50 years old. However, across all age groups, WNT alterations were frequently found in rectal cancers. We also found that WNT alterations were associated with better outcomes. The mutations associated with TGF-beta were observed at a higher rate in older CRC patients when compared to those ≤ 50 years old. Additionally, these mutations were found more frequently in colon primaries.

LC-MS analysis of chiral amino acids in human urine reveals D-amino acids as potential biomarkers for colorectal cancer

Colorectal cancer (CRC) is a common malignant tumor in the gastrointestinal tract. Changes in amino acid metabolites have been implicated in tumorigenesis and disease progression. Biomarkers on the basis of chiral amino acids, especially D-amino acids, have not been established for early diagnosis of CRC. Quantification of chiral amino acids, especially very low concentrations of endogenous D-amino acids, is technically challenging. We report here the quantification of L- and D-amino acids in urine samples collected from 115 CRC patients and 155 healthy volunteers, using an improved method. The method of chiral labeling, liquid chromatography, and tandem mass spectrometry enabled separation and detection of 28 amino acids (14 L-amino acids, 13 D-amino acids and Gly). Orthogonal partial least squares discriminant analysis identified 14 targeted variables among these chiral amino acids that distinguished the CRC from the healthy controls. Binary logistic regression analysis revealed that D-α-aminobutyric acid (D-AABA), L-alanine (L-Ala), D-alanine (D-Ala), D-glutamine (D-Gln) and D-serine (D-Ser) could be potential biomarkers for CRC. A receiver operating characteristic curve analysis of combined multi-variables contributed to an area under the curve (AUC) of 0.995 with 98.3 % sensitivity and 96.8 % specificity. A model constructed with D-AABA, D-Ala, D-Gln, and D-Ser achieved an AUC of 0.988, indicating important contributions of D-amino acids to the association with CRC. Further analysis also demonstrated that the metabolic aberration was associated with age and the development of CRC, D-methionine (D-Met) was decreased in CRC patients with age over 50, and D/L-Gln in patients at stage IV was higher than patients at stage I. This study provides the signature of D-amino acids in urine samples and offers a promising strategy for developing non-invasive diagnosis of CRC.

Colorectal cancer risk stratification using a polygenic risk score in symptomatic primary care patients-a UK Biobank retrospective cohort study.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Accurate cancer risk assessment approaches could increase rates of early CRC diagnosis, improve health outcomes for patients and reduce pressure on diagnostic services. The faecal immunochemical test (FIT) for blood in stool is widely used in primary care to identify symptomatic patients with likely CRC. However, there is a 6-16% noncompliance rate with FIT in clinic and ~90% of patients over the symptomatic 10 µg/g test threshold do not have CRC. A polygenic risk score (PRS) quantifies an individual's genetic risk of a condition based on many common variants. Existing PRS for CRC have so far been used to stratify asymptomatic populations. We conducted a retrospective cohort study of 50,387 UK Biobank participants with a CRC symptom in their primary care record at age 40+. A PRS based on 201 variants, 5 genetic principal components and 22 other risk factors and markers for CRC were assessed for association with CRC diagnosis within 2 years of first symptom presentation using logistic regression. Associated variables were included in an integrated risk model and trained in 80% of the cohort to predict CRC diagnosis within 2 years. An integrated risk model combining PRS, age, sex, and patient-reported symptoms was predictive of CRC development in a testing cohort (receiver operating characteristic area under the curve, ROCAUC: 0.76, 95% confidence interval: 0.71-0.81). This model has the potential to improve early diagnosis of CRC, particularly in cases of patient noncompliance with FIT.

Exploring the role of tRNA-derived small RNAs (tsRNAs) in disease: implications for HIF-1 pathway modulation.

The tRNA-derived small RNAs (tsRNAs) can be categorized into two main groups: tRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs). Each group possesses specific molecular sizes, nucleotide compositions, and distinct physiological functions. Notably, hypoxia-inducible factor-1 (HIF-1), a transcriptional activator dependent on oxygen, comprises one HIF-1β subunit and one HIF-α subunit (HIF-1α/HIF-2α/HIF-3α). The activation of HIF-1 plays a crucial role in gene transcription, influencing key aspects of cancer biology such as angiogenesis, cell survival, glucose metabolism, and invasion. The involvement of HIF-1α activation has been demonstrated in numerous human diseases, particularly cancer, making HIF-1 an attractive target for potential disease treatments. Through a series of experiments, researchers have identified two tiRNAs that interact with the HIF-1 pathway, impacting disease development: 5'tiRNA-His-GTG in colorectal cancer (CRC) and tiRNA-Val in diabetic retinopathy (DR). Specifically, 5'tiRNA-His-GTG promotes CRC development by targeting LATS2, while tiRNA-Val inhibits Sirt1, leading to HIF-1α accumulation and promoting DR development. Clinical data have further indicated that certain tsRNAs' expression levels are associated with the prognosis and pathological features of CRC patients. In CRC tumor tissues, the expression level of 5'tiRNA-His-GTG is significantly higher compared to normal tissues, and it shows a positive correlation with tumor size. Additionally, KEGG analysis has revealed multiple tRFs involved in regulating the HIF-1 pathway, including tRF-Val-AAC-016 in diabetic foot ulcers (DFU) and tRF-1001 in pathological ocular angiogenesis. This comprehensive article reviews the biological functions and mechanisms of tsRNAs related to the HIF-1 pathway in diseases, providing a promising direction for subsequent translational medicine research.

Comparison between 16S rRNA and shotgun sequencing in colorectal cancer, advanced colorectal lesions, and healthy human gut microbiota

BackgroundGut dysbiosis has been associated with colorectal cancer (CRC), the third most prevalent cancer in the world. This study compares microbiota taxonomic and abundance results obtained by 16S rRNA gene sequencing (16S) and whole shotgun metagenomic sequencing to investigate their reliability for bacteria profiling. The experimental design included 156 human stool samples from healthy controls, advanced (high-risk) colorectal lesion patients (HRL), and CRC cases, with each sample sequenced using both 16S and shotgun methods. We thoroughly compared both sequencing technologies at the species, genus, and family annotation levels, the abundance differences in these taxa, sparsity, alpha and beta diversities, ability to train prediction models, and the similarity of the microbial signature derived from these models.ResultsAs expected, the results showed that 16S detects only part of the gut microbiota community revealed by shotgun, although some genera were only profiled by 16S. The 16S abundance data was sparser and exhibited lower alpha diversity. In lower taxonomic ranks, shotgun and 16S highly differed, partially due to a disagreement in reference databases. When considering only shared taxa, the abundance was positively correlated between the two strategies. We also found a moderate correlation between the shotgun and 16S alpha-diversity measures, as well as their PCoAs. Regarding the machine learning models, only some of the shotgun models showed some degree of predictive power in an independent test set, but we could not demonstrate a clear superiority of one technology over the other. Microbial signatures from both sequencing techniques revealed taxa previously associated with CRC development, e.g., Parvimonas micra.ConclusionsShotgun and 16S sequencing provide two different lenses to examine microbial communities. While we have demonstrated that they can unravel common patterns (including microbial signatures), shotgun often gives a more detailed snapshot than 16S, both in depth and breadth. Instead, 16S will tend to show only part of the picture, giving greater weight to dominant bacteria in a sample. Therefore, we recommend choosing one or another sequencing technique before launching a study. Specifically, shotgun sequencing is preferred for stool microbiome samples and in-depth analyses, while 16S is more suitable for tissue samples and studies with targeted aims.

Rare Germline Variants in the Adenomatous Polyposis Coli Gene Associated with Dental and Osseous Anomalies

APC is a tumor suppressor gene that exerts its effect through the regulation of the Wnt signaling pathway. Loss of function mutations of the gene are associated with familial adenomatous polyposis (FAP). Early diagnosis in FAP patients is essential to prevent the development of colorectal cancer. Extraintestinal manifestations often precede the formation of the polyposis; therefore, these manifestations may serve as a clinical indicator for the condition. The aim of this study was to assess genotype–phenotype associations between the location of APC mutations and various extraintestinal features, mainly focusing on osseous and dental anomalies. Analyses of our cases and the mutations available in the literature with these manifestations revealed that mutations in the N-terminal region (amino acids 1–~1000) of the protein are more frequently associated with only osseous anomalies, whereas dental manifestations are more prevalent in mutations in the middle region (amino acids 1000–~2100). In addition, supernumerary teeth were found to be the most common dental feature. Since dental abnormalities often precede intestinal polyposis, dentists have a crucial role in the early identification of patients at risk.

A novel drug prejudice scaffold-imidazopyridine-conjugate can promote cell death in a colorectal cancer model by binding to β-catenin and suppressing the Wnt signaling pathway

IntroductionGlobally, colorectal cancer (CRC) is the third most common type of cancer, and its treatment frequently includes the utilization of drugs based on antibodies and small molecules. The development of CRC has been linked to various signaling pathways, with the Wnt/β-catenin pathway identified as a key target for intervention. ObjectivesWe have explored the impact of imidazopyridine-tethered chalcone-C (CHL-C) in CRC models. MethodsTo determine the influence of CHL-C on apoptosis and autophagy, Western blot analysis, annexin V assay, cell cycle analysis, acridine orange staining, and immunocytochemistry were performed. Next, the activation of the Wnt/β-catenin signaling pathway and the anti-cancer effects of CHL-C in vivo were examined in an orthotopic HCT-116 mouse model. ResultsWe describe the synthesis and biological assessment of the CHL series as inhibitors of the viability of HCT-116, SW480, HT-29, HCT-15, and SNU-C2A CRC cell lines. Further biological evaluations showed that CHL-C induced apoptosis and autophagy in down-regulated β-catenin, Wnt3a, FZD-1, Axin-1, and p-GSK-3β (Ser9), and up-regulated p-GSK3β (Tyr216) and β-TrCP. In-depth analysis using structure-based bioinformatics showed that CHL-C strongly binds to β-catenin, with a binding affinity comparable to that of ICG-001, a well-known β-catenin inhibitor. Additionally, our in vivo research showed that CHL-C markedly inhibited tumor growth and triggered the activation of both apoptosis and autophagy in tumor tissues. ConclusionCHL-C is capable of inducing apoptosis and autophagy by influencing the Wnt/β-catenin signaling pathway.

Gut microbiota affects the activation of STING pathway and thus participates in the progression of colorectal cancer

BackgroundMore and more studies showed that gut microbiota was closely related to the development of colorectal cancer (CRC). However, the specific pathway of gut microbiota regulating CRC development is still unknown.MethodsWe collected fecal samples from 14 CRC patients and 20 normal volunteers for 16 S sequencing analysis. At the same time, 14 CRC patients’ tumors and their adjacent tissues were collected for the detection of STING pathway related protein level. Mice were injected with azoxymethane (AOM) to establish an animal model of CRC, and antibiotics were given at the same time to evaluate the influence of gut microbiota on STING pathway and whether it was involved in regulating the tumor development of CRC mice.ResultsThe sequencing results showed that compared with the normal group, the gut microbiota gut microbiota of CRC patients changed significantly at different species classification levels. At the level of genus, Akkermansia, Ligilactobacillus and Subdoligranulum increased the most in CRC patients, while Bacteroides and Dialister decreased sharply. The expression of STING-related protein was significantly down-regulated in CRC tumor tissues. Antibiotic treatment of CRC mice can promote the development of tumor and inhibit the activation of STING pathway.ConclusionGut microbiota participates in CRC progress by mediating STING pathway activation.

IL-10 polymorphism genotypes, haplotypes, and diplotypes are associated with colorectal cancer predisposition and outcome in Tunisian population

Background and aimAs the presence of single nucleotide polymorphisms (SNPs) in the interleukin (IL)-10 gene continues to be a major challenge in the development of effective therapies for digestive cancers, this case-control study was conducted to assess the possible influence of genotype, haplotype and diplotype for two SNPs (-1082A/G (rs1800896) and -592A/C (rs1800872)) located in the promoter region of IL-10 gene on the incidence, severity and prognosis of colorectal cancer (CRC) in Tunisians. MethodsIL-10 gene SNPs were analysed in 130 CRC cases and 165 healthy subjects (HS) using PCR-SSP. ResultsFor the IL-10 -1082A/G SNP, comparison of genotype frequencies between cases and HS groups showed that the G allele significantly reduced CRC risk under the recessive model (GG vs. AA+AG: OR [95%CI]= 0.44 [0.21-0.93], p= 0.03). Conversely, a positive association was observed between the codominant model (AG vs. AA+GG) and high susceptibility (OR [95%CI]= 1.65 [1.02-2.63], p=0.04). After stratification by disease site, the recessive model was also found to reduce susceptibility to colon cancer (OR [95%CI]= 0.18 [0.04-0.72], p=0 .01), while the homozygote model (AA vs. GG) was suggested as a risk factor (OR [95%CI]= 5.16 [1.31-23.26], p= 0.02). Furthermore, the codominant model (AG vs. AA+GG) doubled the risk of rectum cancer (OR [95%CI]= 1.98 [1.07-3.70], p= 0.03). For the IL-10 -592A/C SNP, the codominant model (AC vs. AA+CC) has a protective effect against the development of CRC (OR [95%CI]= 0.59 [0.36-0.94], p= 0.03). The IL-10 gene haplotype was not associated with CRC risk. A stratified analysis by disease site demonstrated that the presence of Hap3 (-1082G and -592C alleles) specifically reduced the risk of developing colon cancer (OR [95%CI]= 0.51 [0.32-0.80], p= 0.003). Moreover, homozygous Hap3/Hap3 diplotype significantly reduced susceptibility to CRC (OR [95%CI]= 0.35 [0.14-0.85], p= 0.02). Interestingly, this diplotype has not been identified in colon cancer patients. Kaplan-Meier analysis showed that the homozygous Hap2/Hap2 diplotype was significantly associated with decreased overall survival (Log-rank: p=0.01). This association was also observed in the colon cancer subgroup (Log-rank: p=0.001). ConclusionOur findings provide preliminary indications that the -1082A/G and -592/AC SNPs within the IL-10 gene may exhibit significant associations with the pathogenesis and prognostic outcomes of CRC. However, further investigations are still warranted to validate and establish the veracity of our findings.

Defensins: Exploring Their Opposing Roles in Colorectal Cancer Progression

Colorectal cancer (CRC) represents a significant global healthcare burden, with a particularly concerning rising incidence among younger adults. This trend may highlight potential links between diet, gut microbiome, and CRC risk. Novel therapeutic options have been increasingly based on the understanding of molecular mechanisms and pathways. The PI3K/AKT/mTOR pathway, a crucial cell growth regulator, offers a promising target for CRC therapy. mTOR, a key component within this pathway, controls cell growth, survival, and metabolism. Understanding the specific roles of defensins, particularly human β-Defensin 1 (HBD-1), in CRC is crucial. HBD-1 exhibits potent antimicrobial activity and may influence CRC development. Deciphering defensin expression patterns in CRC holds the promise of improved understanding of tumorigenesis, which may pave the way for improved diagnostics and therapies. This article reviews recent advances in understanding regarding how HBD-1 influences CRC initiation and progression, highlighting the molecular mechanisms by which it impacts CRC. Further, we describe the interaction between defensins and mTOR pathway in CRC.

Identification of the M2 Macrophage-associated Gene THBS2 as a Predictive Marker for Inflammatory Cancer Transformation.

Ulcerative colitis (UC)-induced colitis-associated colorectal cancer (CAC) has a worse prognosis than sporadic colorectal cancer. And with the incidence of ulcerative colitis on the rise, it is critical to identify new therapeutic targets in time to stop the progression of inflammation to cancer. Through immunohistochemistry (IHC) and Gene Expression Omnibus (GEO) database analysis, we acquired the gene M2DEG, which is differentially expressed in M2 macrophages. The impact of M2DEG on the immune environment and clinical variables was confirmed through various data sets and actual tissue samples. Our findings indicate that patients with UC exhibiting reduced M2 macrophage infiltration tend to have more widespread disease, elevated endoscopic Mayo scores, and a higher probability of developing CAC. Through examining the string of M2DEG between UC and CAC, THBS2 emerged as a key marker. Elevated levels of THBS2 were notably linked to reduced overall survival (OS) and progression-free survival (RFS), and this heightened THBS2 expression played a crucial role in the spread of tumors, as verified by immunohistochemical studies. To sum up, patients with UC exhibiting reduced M2 macrophage infiltration have a higher propensity for CAC development, making THBS2 a crucial focus for converting UC into CAC. Furthermore, identifying antibody analogues targeting THBS2 could potentially lower the likelihood of CAC transformation in patients with UC.

Retracted] Circular RNA NOX4 promotes the development of colorectal cancer via the microRNA‑485‑5p/CKS1B axis.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that there appeared to be a matching data panel comparing between one of the Transwell invasion assay experiments (the 'SW620/si‑NC' data panel) shown in Fig. 2F and Fig 6D in the following paper, written by different authors at different research institutes, that had already been published at the time of this paper's submission: Wang D, Yang T, Liu J, Liu Y, Xing N, He J, Yang J and Ai Y: Propofol inhibits the migration and invasion of glioma cells by blocking the PI3K/AKT pathway through miR‑206/ROCK1 axis. Onco Targets Ther 13: 361‑370, 2020. In addition, a potential problem regarding the design of the experiment was noted with the selection of the primers for the amplification of the miRNA miR‑485‑5p. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 44: 2009‑2020, 2020; DOI: 10.3892/or.2020.7758].

The Role and Therapeutic Potential of Pyroptosis in Colorectal Cancer: A Review.

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. The unlimited proliferation of tumor cells is one of the key features resulting in the malignant development and progression of CRC. Consequently, understanding the potential proliferation and growth molecular mechanisms and developing effective therapeutic strategies have become key in CRC treatment. Pyroptosis is an emerging type of regulated cell death (RCD) that has a significant role in cells proliferation and growth. For the last few years, numerous studies have indicated a close correlation between pyroptosis and the occurrence, progression, and treatment of many malignancies, including CRC. The development of effective therapeutic strategies to inhibit tumor growth and proliferation has become a key area in CRC treatment. Thus, this review mainly summarized the different pyroptosis pathways and mechanisms, the anti-tumor (tumor suppressor) and protective roles of pyroptosis in CRC, and the clinical and prognostic value of pyroptosis in CRC, which may contribute to exploring new therapeutic strategies for CRC.

Mechanistic exploration of 6-shogaol’s preventive effects on azoxymethane and dextran sulfate sodium -induced colorectal cancer: involvement of cell proliferation, apoptosis, carcinoembryonic antigen, wingless-related integration site signaling, and oxido-inflammation

Colorectal cancer (CRC) poses a significant global health burden, being the third most prevalent cancer and the second most significant contributor to cancer-related deaths worldwide. Preventive strategies are crucial to combat this rising incidence. 6-shogaol, derived from ginger, has shown promise in preventing and treating various cancers. This study investigated the preventive effects of 6-shogaol on azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC in mice. Forty male BALB/c mice were randomly divided into control, 6-shogaol, AOM + DSS, and 6-shogaol + AOM + DSS. Mice in the control group received corn oil for 16 weeks, while those in the 6-Shogaol group were administered 20 mg/kg of 6-shogaol for 16 weeks. The AOM + DSS group received a single intraperitoneal dose (ip) of 10 mg/kg of AOM, followed by three cycles of 2.5% DSS in drinking water. The 6-shogaol + AOM + DSS group received both 6-shogaol for 16 weeks and a single ip of 10 mg/kg of AOM, followed by three cycles of 2.5% DSS in drinking water. The AOM + DSS-treated mice exhibited reduced food consumption, colon weight, and colon length, along with increased tumor formation. Co-administration of 6-shogaol effectively reversed these changes, inhibiting CRC development. Histopathological analysis revealed protective effects of 6-shogaol against colonic insults and modulation of inflammatory responses. 6-shogaol significantly reduced Carcinoembryonic antigen and Kiel 67 levels, indicating inhibition of tumor cell proliferation. Mechanistically, 6-shogaol promoted apoptosis by upregulating protein 53 and caspase-3 expression, and it effectively restored the balance of the Wingless-related integration site signaling pathway by regulating β-catenin and adenomatous polyposis coli levels. Moreover, 6-shogaol demonstrated anti-inflammatory effects, reducing myeloperoxidase, Tumor necrosis factor alpha, and cyclooxygenase-2 levels in AOM/DSS-treated mice. Additionally, 6-shogaol restored redox homeostasis by reducing lipid peroxidation and nitrosative stress and enhancing antioxidant enzyme activities. The findings suggest that 6-shogaol inhibits cell proliferation, induces apoptosis, regulates Wnt signaling, suppresses inflammation, and restores redox homeostasis, providing comprehensive insights into its potential therapeutic benefits for CRC.

Gut Microbiota Signatures in Colorectal Cancer as a Potential Diagnostic Biomarker in the Future: A Systematic Review.

The gut microbiota has acquired significant attention in recent years for its potential as a diagnostic biomarker for colorectal cancer (CRC). In this literature review, we looked at the studies exploring alterations in gut microbiota composition associated with CRC, the potential mechanisms linking gut dysbiosis to CRC development, and the diagnostic approaches utilizing gut microbiota analysis. Our research has led to the conclusion that individuals with CRC often display alterations in their gut microbiota composition compared to healthy individuals. These alterations can include changes in the diversity, abundance, and type of bacteria present in the gut. While the use of gut microbiota as a diagnostic biomarker for CRC holds promise, further research is needed to validate its effectiveness and standardize testing protocols. Additionally, considerations such as variability in the microbiota composition among individuals and potential factors must be addressed before microbiota-based tests can be widely implemented in clinical practice.