MiRNA expression affects survival in patients with obstructive sleep apnea and metastatic colorectal cancer.

Introduction: The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs. Methods: The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients' sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs. Results: The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly. Conclusions: This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.

Tubeimoside-I, an inhibitor of HSPD1, enhances cytotoxicity of oxaliplatin by activating ER stress and MAPK signaling pathways in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Tubeimoside-I (TBM) promotes various cancer cell death by increasing the reactive oxygen species (ROS) production. However, the specific molecular mechanisms of TBM and its impact on oxaliplatin-mediated anti-CRC activity are not yet fully understood. AIM OF THE STUDY: To elucidate the therapeutic effect and underlying molecular mechanism of TBM on oxaliplatin-mediated anti-CRC activity. MATERIALS AND METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing assays and flow cytometry were conducted to investigate the changes in cell phenotypes and ROS generation. Real-time quantitative PCR (qRT-PCR) and western blotting were performed to detect the expressions of related mRNA and proteins. Finally, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with TBM and oxaliplatin. RESULTS: The synergistic enhancement of the anti-tumor effects of oxaliplatin in colon cancer cells by TBM involved in the regulation of ROS-mediated endoplasmic reticulum (ER) stress, C-jun-amino-terminal kinase (JNK), and p38 MAPK signaling pathways. Mechanistically, TBM increased ROS generation in colon cancer cells by inhibiting heat shock protein 60 (HSPD1) expression. Knocking down HSPD1 increased TBM-induced antitumor activity and ROS generation in colon cancer cells. The mouse xenograft tumor models further validated that the combination therapy exhibited stronger anti-tumor effects than monotherapy alone. CONCLUSIONS: Combined therapy with TBM and oxaliplatin might be an effective therapeutic strategy for some CRC patients.

The influence of color vision deficiency on vessel visibility during colorectal endoscopic submucosal dissection and the potential advantage of red dichromatic imaging to achieve color vision barrier-free.

Objectives: Although color information is important in gastrointestinal endoscopy, there are limited studies on how endoscopic images are viewed by people with color vision deficiency. We aimed to investigate the differences in the visibility of blood vessels during endoscopic submucosal dissection (ESD) among people with different color vision characteristics and to examine the effect of red dichromatic imaging (RDI) on blood vessel visibility. Methods: Seventy-seven pairs of endoscopic images of white light imaging (WLI) and RDI of the same site were obtained during colorectal ESD. The original images were set as type C (WLI-C and RDI-C), a common color vision. These images were computationally converted to simulate images perceived by people with color vision deficiency protanope (Type P) or deutanope (Type D) and denoted as WLI-P and RDI-P or WLI-D and RDI-D. Blood vessels and background submucosa that needed to be identified during ESD were selected in each image, and the color differences between these two objects were measured using the color difference (ΔE 00) to assess the visibility of blood vessels. Results: ΔE 00 between a blood vessel and the submucosa was greater under RDI (RDI-C/P/D: 24.05 ± 0.64/22.85 ± 0.66/22.61 ± 0.64) than under WLI (WLI-C/P/D: 22.26 ± 0.60/5.19 ± 0.30/8.62 ± 0.42), regardless of color vision characteristics. This improvement was more pronounced in Type P and Type D and approached Type C in RDI. Conclusions: Color vision characteristics affect the visibility of blood vessels during ESD, and RDI improves blood vessel visibility regardless of color vision characteristics.

Analysis of lens cloudiness during endoscopic submucosal dissection procedures: Effects of a novel lens cleaner.

Objectives: We aimed to identify independent factors for intraoperative endoscopic lens cloudiness during gastric and colorectal endoscopic submucosal dissections, investigate the effectiveness of Cleastay, an endoscope anti-fog solution, and examine factors associated with severe submucosal fat deposition. Methods: A total of 220 patients who underwent gastric or colorectal endoscopic submucosal dissections in two institutions between January 2022 and October 2023 were included. Significant factors related to cloudiness were determined using univariate and multivariate analyses. Patient background and tumor characteristics related to severe submucosal fat deposition were investigated, and the degree of intraoperative endoscopic lens cloudiness and outcomes were compared between the Cleash and Cleastay groups. Results: In the multivariate analysis, factors increasing lens cloudiness included long procedure time (odds ratio [OR], 17.51; 95% confidence interval [CI], 1.52-202.08), stomach (vs. colon; OR, 5.08; 95% CI, 1.99-12.96), and severe submucosal fat deposition (OR, 12.19; 95% CI, 5.02-29.60). Conversely, the use of Cleastay (vs. Cleash; OR, 0.066; 95% CI, 0.021-0.21) was identified as a factor reducing cloudiness. Location analysis revealed that severe submucosal fat deposition was more common in the upper stomach and right colon. Conclusions: It was suggested that Cleastay is more useful for endoscopic submucosal dissection of the upper stomach and right colon, where severe submucosal fat deposition is expected.

Safety and efficacy of low-power pure-cut hot snare polypectomy for small nonpedunculated colorectal polyps compared with conventional resection methods: A propensity score matching analysis.

Objectives: Cold snare polypectomy (CSP) is widely performed for small colorectal polyps. However, small colorectal polyps sometimes include high-grade adenomas or carcinomas that require endoscopic resection with electrocautery. This study aimed to evaluate the efficacy and safety of a novel resection technique, hot snare polypectomy with low-power pure-cut current (LPPC-HSP) for small colorectal polyps, compared with CSP and conventional endoscopic mucosal resection (EMR). Methods: Records of patients who underwent CSP, EMR, or LPPC-HSP for nonpedunculated colorectal polyps less than 10 mm between April 2021 and March 2022 were retrospectively evaluated. We analyzed and compared the treatment outcomes of CSP and EMR with those of LPPC-HSP using propensity score matching. Results: After propensity score matching of 396 pairs, an analysis of CSP and LPPC-HSP indicated that LPPC-HSP had a significantly higher R0 resection rate (84% vs. 68%; p < 0.01). Delayed bleeding was observed in only two cases treated with CSP before matching. Perforation was not observed with either treatment. After propensity score matching of 176 pairs, an analysis of EMR and LPPC-HSP indicated that their en bloc and R0 resection rates were not significantly different (99.4% vs. 100%, p = 1.00; 79% vs. 81%, p = 0.79). Delayed bleeding and perforation were not observed with either treatment. Conclusions: The safety of LPPC-HSP was comparable to that of CSP. The treatment outcomes of LPPC-HSP were comparable to those of conventional EMR for small polyps. These results suggest that this technique is a safe and effective treatment for nonpedunculated polyps less than 10 mm.

Efficacy of texture and color enhancement imaging for the visibility and diagnostic accuracy of non-polypoid colorectal lesions.

Objective: A newly launched endoscopy system (EVIS X1, CV-1500; Olympus) is equipped with texture and color enhancement imaging (TXI). We aimed to investigate the efficacy of TXI for the visibility and diagnostic accuracy of non-polypoid colorectal lesions. Methods: We examined 100 non-polypoid lesions in 42 patients from the same position, angle, and distance of the view in three modes: white light imaging (WLI), narrow-band imaging (NBI), and TXI. The primary outcome was to compare polyp visibility in the three modes using subjective polyp visibility score and objective color difference values. The secondary outcome was to compare the diagnostic accuracy without magnification. Results: Overall, the visibility score of TXI was significantly higher than that of WLI (3.7 ± 1.1 vs. 3.6 ± 1.1; p = 0.008) and lower than that of NBI (3.7 ± 1.1 vs. 3.8 ± 1.1; p = 0.013). Color difference values of TXI were higher than those of WLI (11.5 ± 6.9 vs. 9.1 ± 5.4; p < 0.001) and lower than those of NBI (11.5 ± 6.9 vs. 13.1 ± 7.7; p = 0.002). No significant differences in TXI and NBI (visibility score: 3.7 ± 1.0 vs. 3.8 ± 1.1; p = 0.833, color difference values: 11.6 ± 7.1 vs. 12.9 ± 8.3; p = 0.099) were observed for neoplastic lesions. Moreover, the diagnostic accuracy of TXI was significantly higher than that of NBI (65.5% vs. 57.6%, p = 0.012) for neoplastic lesions. Conclusions: TXI demonstrated higher visibility than that of WLI and lower than that of NBI. Further investigations are warranted to validate the performance of the TXI mode comprehensively.

Self-assembled PROTACs enable protein degradation to reprogram the tumor microenvironment for synergistically enhanced colorectal cancer immunotherapy.

Both ß-catenin and STAT3 drive colorectal cancer (CRC) growth, progression, and immune evasion, and their co-overexpression is strongly associated with a poor prognosis. However, current small molecule inhibitors have limited efficacy due to the reciprocal feedback activation between STAT3 and ß-catenin. Inspired by the PROteolysis TArgeting Chimera (PROTAC), a promising pharmacological modality for the selective degradation of proteins, we developed a strategy of nanoengineered peptide PROTACs (NP-PROTACs) to degrade both ß-catenin and STAT3 effectively. The NP-PROTACs were engineered by coupling the peptide PROTACs with DSPE-PEG via disulfide bonds and self-assembled into nanoparticles. Notably, the dual degradation of ß-catenin and STAT3 mediated by NP-PROTACs led to a synergistic antitumor effect compared to single-target treatment. Moreover, NP-PROTACs treatment enhanced CD103+ dendritic cell infiltration and T-cell cytotoxicity, alleviating the immunosuppressive microenvironment induced by ß-catenin/STAT3 in CRC. These results highlight the potential of NP-PROTACs in facilitating the simultaneous degradation of two pathogenic proteins, thereby providing a novel avenue for cancer therapy.

Genes da instabilidade de microssatélites no câncer colorretal: papel na inflamação e estresse oxidativo / Microsatellite instability genes in colorectal cancer: role in inflammation and oxidative stress

A instabilidade de microssatélites é um fenômeno genético caracterizado pela alteração na repetição de sequências de nucleotídeos conhecidas como microssatélites. Esta instabilidade pode ocorrer devido a defeitos nos genes reparadores de DNA, como os genes MLH1, MSH2, MSH6 e PMS2. A inflamação crônica tem sido associada ao desenvolvimento do câncer colorretal. Os genes da instabilidade de microssatélites estão envolvidos na regulação da resposta inflamatória, podendo influenciar a progressão tumoral. Estudos demonstraram que a presença de instabilidade de microssatélites em tumores colorretais está relacionada a uma maior infiltração de células imunes, como linfócitos T, macrófagos e neutrófilos, que podem modular a resposta inflamatória no microambiente tumoral. O estresse oxidativo é caracterizado pelo desequilíbrio entre a produção de espécies reativas de oxigênio e a capacidade antioxidante do organismo e desempenha um papel importante na carcinogênese. Os genes da instabilidade de microssatélites podem influenciar a resposta ao estresse oxidativo, afetando a capacidade das células tumorais de lidar com o dano oxidativo e promovendo a sobrevivência celular. O objetivo deste trabalho consiste na compreensão dos genes envolvidos na instabilidade de microssatélites no câncer colorretal e como eles contribuem para o desenvolvimento da doença, relacionando com processos inflamatórios e estresse oxidativo nas células tumorais. Justifica-se pela necessidade de compreensão das interconexões entre a instabilidade de microssatélites, inflamação e o estresse oxidativo em pacientes com câncer colorretal.

Microsatellite instability is a genetic phenomenon characterized by changes in the repetition of nucleotide sequences known as microsatellites. This instability may occur due to defects in DNA repair genes, such as the MLH1, MSH2, MSH6 and PMS2 genes. Chronic inflammation has been linked to the development of colorectal cancer. Microsatellite instability genes are involved in regulating the inflammatory response and may influence tumor progression. Studies have shown that the presence of microsatellite instability in colorectal tumors is related to a greater infiltration of immune cells, such as T lymphocytes, macrophages and neutrophils, which can modulate the inflammatory response in the tumor microenvironment. Oxidative stress is characterized by the imbalance between the production of reactive oxygen species and the body's antioxidant capacity and plays an important role in carcinogenesis. Microsatellite instability genes can influence the response to oxidative stress, affecting the ability of tumor cells to deal with oxidative damage and promoting cell survival. The objective of this work is to understand the genes involved in microsatellite instability in colorectal cancer and how they contribute to the development of the disease, relating it to inflammatory processes and oxidative stress in tumor cells. It is justified by the need to understand the interconnections between microsatellite instability, inflammation and oxidative stress in patients with colorectal cancer.

Fostering collaboration: an exploration of knowledge exchange between Rongoa Maori practitioners and surgical clinicians.

BACKGROUND: This research investigates the potential for collaboration of Rongoa Maori, the Indigenous healing practices of Maori, with New Zealand's contemporary healthcare system. It aims to bridge the gap between Rongoa Maori and Western medicine by exploring the perspectives of practitioners from both fields, identifying barriers to integration, and highlighting potential areas for collaboration. METHODS: Qualitative interviews were conducted with both Rongoa practitioners and Western surgeons. The data collected were subjected to thematic analysis to extract key themes related to the integration process, challenges faced, and the potential for mutual recognition and respect between the two healing paradigms. RESULTS: The study reveals a deep respect for Rongoa Maori among Western surgeons but identifies significant systemic barriers that impede its integration. These include bureaucratic challenges and the absence of clear referral pathways. Rongoa practitioners express concerns over being overlooked within the healthcare system and highlight a lack of awareness among healthcare professionals about their practices. Despite these challenges, there is a shared interest in collaborative approaches to healthcare that respect and incorporate Rongoa Maori. CONCLUSIONS: The findings underscore the need for systemic changes to facilitate the integration of Rongoa Maori into mainstream healthcare, including the development of clear referral pathways and initiatives to raise awareness among healthcare professionals. The study highlights the need for a more collaborative healthcare approach that values the contributions of Rongoa Maori, aiming to improve patient care through holistic practices.

Mechanism of Guishao Yigong decoction in treating colorectal cancer based on network pharmacology and experimental validation.

OBJECTIVES: To explore the effective components of Guishao Yigong decoction (GYD) in the treatment of colorectal cancer and reveal its potential mechanism of action. METHODS: Through network pharmacology, the main target and signaling pathway of GYD therapy for colorectal cancer (CRC) were found. Subsequently, the effect of GYD was verified by in vitro cell viability measurements, colony formation, and scratch healing tests. The effects of GYD on metabolic pathways in vivo were found through plasma metabolomics. Finally, flow cytometry and qPCR experiments were used to verify the cycle-blocking effect of GYD on CRC cells. KEY FINDINGS: Based on the network pharmacological analysis and molecular docking technology, it was found that GYD could restrain the growth of CRC cells by affecting lipid metabolic pathways and mitogen-activated protein kinase (MAPK) signaling pathways. A series of cell experiments showed that GYD could inhibit the proliferation, migration and clonogenic ability of CRC cells. Furthermore, the plasma metabolomics results showed that GYD could affect the production of unsaturated fatty acids in mice. Flow cytometry and qPCR experiments further proved that GYD blocked the CRC cells in the G1 phase and modulated the expression of cell cycle-related targets, such as AKT, TP53, CDKN1A, and CDK2. CONCLUSIONS: All the results indicated that GYD could regulate the related metabolism of unsaturated fatty acids. Thus, the cell cycle was blocked and the expressions of the key proteins such as AKT and TP53 were regulated, which achieved the purpose of intervention in colorectal cancer.

Preoperative very low-energy diets for obese patients undergoing intra-abdominal colorectal surgery: a retrospective cohort study (RetroPREPARE).

BACKGROUND: Very low-energy diets (VLEDs) prescribed prior to bariatric surgery have been associated with decreased operative time, technical difficulty, and postoperative morbidity. To date, limited data are available regarding the impact of VLEDs prior to colorectal surgery. We designed this study to determine whether preoperative VLEDs benefit patients with obesity undergoing colorectal surgery. METHODS: This is a single-center retrospective cohort study. Individuals undergoing elective colorectal surgery with a body mass index (BMI) of greater than 30 kg/m2 from 2015 to 2022 were included. The exposure of interest was VLEDs for 2-4 weeks immediately prior to surgery. The control group consisted of patients prior to January 2018 who did not receive preoperative VLED. The primary outcome was 30 day postoperative morbidity. Multivariable logistic regression modeling was used to determine associations with 30 day postoperative morbidity. RESULTS: Overall, 190 patients were included, 89 patients received VLEDs (median age: 66 years; median BMI: 35.9 kg/m2; 48.3% female) and 101 patients did not receive VLEDs (median age: 68 years; median BMI: 32.1 kg/m2; 44.6% female). One-hundred four (54.7%) patients experienced 30 day postoperative morbidity. Multivariable regression analysis identified three variables associated with postoperative morbidity: VLEDs [odds ratio (OR) 0.22, 95% confidence intervals (CI) 0.08-0.61, P < 0.01], Charlson comorbidity index (OR 1.25, 95% CI 1.03-1.52, P = 0.02), and rectal dissections (OR 2.71, 95% CI 1.30-5.65, P < 0.01). CONCLUSIONS: The use of a preoperative VLED was associated with a significant reduction in postoperative morbidity in patients with obesity prior to colorectal surgery. A high-quality randomized controlled trial is required to confirm these findings.

DNA methylation analysis of the SDC2, SEPT9 and VIM genes in fecal DNA for colorectal cancer diagnosis.

BACKGROUND: Colorectal cancer is one of the most common cancers worldwide. DNA methylation sites may serve as a new gene signature for colorectal cancer diagnosis. The search for representative DNA methylation sites is urgently needed. This study aimed to systematically identify a methylation gene panel for colorectal cancer diagnosis via tissue and fecal samples. METHODS: A total of 181 fecal and 50 tumor tissue samples were collected. They were obtained from 83 colorectal cancer patients and 98 healthy subjects. These samples were evaluated for DNA methylation of 9 target genes via quantitative bisulfite next-generation sequencing. We employed the rank-sum test to screen the colorectal cancer-specific methylation sites in the tissue and fecal cohorts. A data model was subsequently constructed and validated via the dedicated validation dataset. RESULTS: Compared with the fecal and negative control samples, the colorectal cancer tissue samples presented significantly higher methylation rates for all the selected gene sites. The methylation rates of the tissue and preoperative fecal samples showed the same high and low rates at the same sites. After screening, a panel of 29 loci in the SDC2, SEPT9, and VIM genes proved to be reliable biomarkers for colorectal cancer diagnosis in fecal samples. Logistic regression models were then constructed and validated using this panel. The sensitivity of the model was 91.43% (95% CI = [89.69, 93.17]), the specificity was 100% (95% CI = [100,100]), and the AUC value is 99.31% (95% CI = [99,99.62]). The diagnostic accuracy of the model for stage I and stage II colorectal cancer was 100% (11/11) and 91.3% (21/23), respectively. Overall, this study confirms that the gene locus panel and the model can be used to diagnose colorectal cancer effectively through feces. CONCLUSIONS: Our study identified a set of key methylation sites for colorectal cancer diagnosis from fecal samples, highlighting the importance of using tissue and fecal samples to accurately assess DNA methylation levels to screen for methylation sites, and developing an effective diagnostic model for colorectal cancer.

Copy number amplification-induced overexpression of lncRNA LOC101927668 facilitates colorectal cancer progression by recruiting hnRNPD to disrupt RBM47/p53/p21 signaling.

BACKGROUND: Somatic copy number alterations (SCNAs) are pivotal in cancer progression and patient prognosis. Dysregulated long non-coding RNAs (lncRNAs), modulated by SCNAs, significantly impact tumorigenesis, including colorectal cancer (CRC). Nonetheless, the functional significance of lncRNAs induced by SCNAs in CRC remains largely unexplored. METHODS: The dysregulated lncRNA LOC101927668, induced by copy number amplification, was identified through comprehensive bioinformatic analyses utilizing multidimensional data. Subsequent in situ hybridization was employed to ascertain the subcellular localization of LOC101927668, and gain- and loss-of-function experiments were conducted to elucidate its role in CRC progression. The downstream targets and signaling pathway influenced by LOC101927668 were identified and validated through a comprehensive approach, encompassing RNA sequencing, RT-qPCR, Western blot analysis, dual-luciferase reporter assay, evaluation of mRNA and protein degradation, and rescue experiments. Analysis of AU-rich elements (AREs) within the mRNA 3' untranslated region (UTR) of the downstream target, along with exploration of putative ARE-binding proteins, was conducted. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and dual-luciferase reporter assays were employed to elucidate potential interacting proteins of LOC101927668 and further delineate the regulatory mechanism between LOC101927668 and its downstream target. Moreover, subcutaneous xenograft and orthotopic liver xenograft tumor models were utilized to evaluate the in vivo impact of LOC101927668 on CRC cells and investigate its correlation with downstream targets. RESULTS: Significantly overexpressed LOC101927668, driven by chr7p22.3-p14.3 amplification, was markedly correlated with unfavorable clinical outcomes in our CRC patient cohort, as well as in TCGA and GEO datasets. Moreover, we demonstrated that enforced expression of LOC101927668 significantly enhanced cell proliferation, migration, and invasion, while its depletion impeded these processes in a p53-dependent manner. Mechanistically, nucleus-localized LOC101927668 recruited hnRNPD and translocated to the cytoplasm, accelerating the destabilization of RBM47 mRNA, a transcription factor of p53. As a nucleocytoplasmic shuttling protein, hnRNPD mediated RBM47 destabilization by binding to the ARE motif within RBM47 3'UTR, thereby suppressing the p53 signaling pathway and facilitating CRC progression. CONCLUSIONS: The overexpression of LOC101927668, driven by SCNAs, facilitates CRC proliferation and metastasis by recruiting hnRNPD, thus perturbing the RBM47/p53/p21 signaling pathway. These findings underscore the pivotal roles of LOC101927668 and highlight its therapeutic potential in anti-CRC interventions.

Who should be screened for colorectal cancer and how can it be prevented more effectively?

In this editorial, we comment on the article published by Agatsuma et al in a recent issue of the World J Gastroenterol (2024; 30: 1368-1376). We firmly concur with Agatsuma et al regarding the vital significance of colorectal cancer (CRC) screening as a public health strategy to diminish disease burden. Individuals exposed to risk factors for CRC, those with comorbid conditions, and those with limited health literacy should undergo screening. However, we believe that more regular screenings should be accompanied by a greater focus on primary prevention (PP) of CRC. CRC remains a significant global health challenge, and its incidence is strongly linked to age, lifestyle, and socioeconomic factors. It is particularly noteworthy that the majority of CRC patients are diagnosed outside of established screening pathways and frequently at an advanced stage of the disease, and the majority of patients possess inadequate or even nonexistent knowledge regarding CRC, which significantly impacts the prognosis and imposes a substantial economic burden. This study revealed that CRC identified during hospital visits for comorbid conditions was typically diagnosed at an earlier stage than detected via symptomatic pathways. Remarkably, early incidental detection of CRC aligns closely with the timing of discovery through routine cancer screenings. This suggests that by adopting more inclusive screening protocols that combine opportunistic testing with traditional screening methods, health care systems can create a more comprehensive safety net for individuals at risk of CRC. However, before maximizing the health benefits of screening programs, it is essential to make additional efforts prior to screening, such as raising awareness via public education, risk assessment, and personalized recommendations, enhancing the knowledge and skills of health care professionals, optimizing the accessibility and convenience of screening processes, ensuring the quality and safety of screening services, strengthening follow-up and support systems, and providing policy support and financial investment. The establishment of a comprehensive screening system often requires substantial investment in human, material, and financial resources, which can be challenging to achieve in regions with limited health care resources. Strengthening PP strategies can reduce the disease burden by targeting the cause, representing a more cost-effective and impactful approach. Establishing a comprehensive cancer PP service platform that integrates authoritative public education on malignant tumor PP, individualized malignant tumor risk assessment, and self-health management assistance accessible to the entire population will significantly enhance the overall effectiveness of CRC PP strategies.

Clinical significance of peripheral blood UL16 and DR-70 for the early diagnosis and prognostic evaluation of colorectal cancer.

BACKGROUND: Early diagnosis of colorectal cancer (CRC) is of great significance to improve the survival rate and quality of life of patients, but early diagnosis of CRC requires more sensitive techniques. Peripheral blood UL16-binding protein 2 (ULBP2) and human fibrinogen degradation products (DR-70) are the main indicators for the diagnosis of malignant tumors. AIM: To assess ULBP2 and DR-70 potential for the early diagnosis and prognostic evaluation of CRC to provide a reference. METHODS: This study involved 60 patients with early-stage CRC (CRC group), 50 patients with benign colorectal tumors (benign group), and 50 healthy patients (control group) enrolled at the Affiliated Hospital of Jiangnan University and Jiangsu Province Official Hospital between January, 2020 and January, 2022. ULBP2 and DR-70 levels in the blood were determined and differences among the three groups and early diagnostic values for CRC were determined. Patients with CRC were divided into the good prognosis and poor prognosis groups, and ULBP2 and DR-70 levels in the blood and diagnostic values were compared. RESULTS: ULBP2 and DR-70 serum levels were significantly higher in the CRC group than in the control and benign groups (P < 0.05); however, no significant differences were observed between the benign and control groups (P > 0.05). Among the 60 patients with CRC followed up for two years, two died (3.33%) and 15 exhibited tumor metastasis, progression, or recurrence (25.00%). ULBP2 and DR-70 serum levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). A receiver operating characteristic curve was plotted. Area under the curve, sensitivity, and specificity of serum ULBP2 with DR-70 for the early diagnosis of CRC were higher than those of the single serum indices (P < 0.05) in both the good and poor prognosis groups. CONCLUSION: ULBP2 and DR-70 serum levels were significantly high in patients with early-stage CRC. They improved the diagnostic rate of early-stage CRC and predicted patient prognosis, thereby showing clinical application potential.

Erythropoietin-induced hepatocyte receptor A2 regulates effect of pyroptosis on gastrointestinal colorectal cancer occurrence and metastasis resistance.

Erythropoietin-induced hepatocyte receptor A2 (EphA2) is a receptor tyrosine kinase that plays a key role in the development and progression of a variety of tumors. This article reviews the expression of EphA2 in gastrointestinal (GI) colorectal cancer (CRC) and its regulation of pyroptosis. Pyroptosis is a form of programmed cell death that plays an important role in tumor suppression. Studies have shown that EphA2 regulates pyrodeath through various signaling pathways, affecting the occurrence, development and metastasis of GI CRC. The overexpression of EphA2 is closely related to the aggressiveness and metastasis of GI CRC, and the inhibition of EphA2 can induce pyrodeath and improve the sensitivity of cancer cells to treatment. In addition, EphA2 regulates intercellular communication and the microenvironment through interactions with other cytokines and receptors, further influencing cancer progression. The role of EphA2 in GI CRC and its underlying mechanisms provide us with new perspectives and potential therapeutic targets, which have important implications for future cancer treatment.

Impact of preoperative inflammatory and nutritional markers on the prognosis of patients with peritoneal metastasis of colorectal cancer.

BACKGROUND: Identifying patients with peritoneal metastasis (PMs) of colorectal cancer (CRC) who will benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is crucial before surgery. Inflammatory and nutritional indicators play essential roles in cancer development and metastasis. AIM: To investigate the association of preoperative inflammatory and nutritional markers with prognosis in patients with CRC-PM. METHODS: We included 133 patients diagnosed with CRC-PM between July 2012 and July 2018. Patients' demographics, overall survival (OS), and preoperative inflammatory and nutritional markers were evaluated. The Kaplan-Meier method and log-rank test were used to estimate differences. RESULTS: Of the 133 patients, 94 (70.6%) had normal hemoglobin (Hb) and 54 (40.6%) had a high neutrophil-to-lymphocyte ratio (NLR). The median OS (mOS) was significantly lower for patients with high NLR (7.9 months) than for those with low NLR (25.4 months; P = 0.002). Similarly, patients with normal Hb had a longer mOS (18.5 months) than those with low Hb (6.3 months; P < 0.001). Multivariate analysis identified age, carbohydrate antigen 199 levels, NLR, Hb, and peritoneal cancer index as independent predictors of OS. Based on these findings, a nomogram was constructed, which demonstrated a good capacity for prediction, with a C-index of 0.715 (95% confidence interval: 0.684-0.740). Furthermore, the 1- and 2-year survival calibration plots showed good agreement between predicted and actual OS rates. The areas under the curve for the 1- and 2-year survival predictions of the nomogram were 0.6238 and 0.6234, respectively. CONCLUSION: High NLR and low Hb were identified as independent predictive risk factors for poor prognosis in patients with CRC-PM. The established nomogram demonstrated high accuracy in predicting OS for patients with CRC-PM, indicating its potential as a valuable prognostic tool for this patient population.

Dyadic effects of perceived stress, relationship satisfaction and distress disclosure on emotional distress in colorectal cancer patients and their family caregivers: An actor-partner interdependence mediation model.

Objective: This study adopted a dyadic analysis method to examine the effect of perceived stress on emotional distress and determine whether relationship satisfaction and distress disclosure act as mediators in colorectal cancer (CRC) enterostomy patient-caregiver dyads. Methods: A total of 312 patient-caregiver dyads completed measures assessing perceived stress, relationship satisfaction, distress disclosure, and emotional distress. The data were analyzed using the actor-partner interdependence mediation model. Results: This study found that the perceived stress of patients and caregivers both had direct and indirect actor effects on emotional distress (through relationship satisfaction). Another important finding is that perceived stress had indirect actor-partner effects (through distress disclosure) on emotional distress. Conclusions: This study highlights that perceived stress, relationship satisfaction, and distress disclosure of patients and their caregivers are key factors that can be considered for improving emotional distress. It also partially confirmed the interdependence of patients with CRC and their caregivers.

Beyond bacteria: Role of non-bacterial gut microbiota species in inflammatory bowel disease and colorectal cancer progression.

This letter emphasizes the need to expand discussions on gut microbiome's role in inflammatory bowel disease (IBD) and colorectal cancer (CRC) by including the often-overlooked non-bacterial components of the human gut flora. It highlights how viral, fungal and archaeal inhabitants of the gut respond towards gut dys-biosis and contribute to disease progression. Viruses such as bacteriophages target certain bacterial species and modulate the immune system. Other viruses found associated include Epstein-Barr virus, human papillomavirus, John Cunningham virus, cytomegalovirus, and human herpes simplex virus type 6. Fungi such as Candida albicans and Malassezia contribute by forming tissue-invasive filaments and producing inflammatory cytokines, respectively. Archaea, mainly metha-nogens are also found altering the microbial fermentation pathways. This corres-pondence, thus underscores the significance of considering the pathological and physiological mechanisms of the entire spectrum of the gut microbiota to develop effective therapeutic interventions for both IBD and CRC.

Colorectal cancer cell dormancy: An insight into pathways.

Cancer cell dormancy (CCD) in colorectal cancer (CRC) poses a significant challenge to effective treatment. In CRC, CCD contributes to tumour recurrence, drug resistance, and amplifying the disease's burden. The molecular mechanisms governing CCD and strategies for eliminating dormant cancer cells remain largely unexplored. Therefore, understanding the molecular mechanisms governing dormancy is crucial for improving patient outcomes and developing targeted therapies. This editorial highlights the complex interplay of signalling pathways and factors involved in colorectal CCD, emphasizing the roles of Hippo/YAP, pluripotent transcription factors such as NANOG, HIF-1α signalling, and Notch signalling pathways. Additionally, ERK/p38α/ß/MAPK pathways, AKT signalling pathway, and Extracellular Matrix Metalloproteinase Inducer, along with some potential less explored pathways such as STAT/p53 switch and canonical and non-canonical Wnt and SMAD signalling, are also involved in promoting colorectal CCD. Highlighting their clinical significance, these findings may offer the potential for identifying key dormancy regulator pathways, improving treatment strategies, surmounting drug resistance, and advancing personalized medicine approaches. Moreover, insights into dormancy mechanisms could lead to the development of predictive biomarkers for identifying patients at risk of recurrence and the tailoring of targeted therapies based on individual dormancy profiles. It is essential to conduct further research into these pathways and their modulation to fully comprehend CRC dormancy mechanisms and enhance patient outcomes.