Chemoresistance represents a major issue affecting cancer therapy efficacy. Because microRNAs (miRNAs) regulate gene expression on multiple levels, their role in chemoresistance development is reasonably certain. In our previous study, miR-122-5p and miR-142-5p were identified as diagnostic, prognostic, and predictive biomarkers for primary and metastatic rectal cancer. The aim of the present study was to investigate whether these miRNAs can also reflect the disease course of patients with colon cancer (CC). Further, we focused on a deeper understanding of their involvement in 5-fluorouracil (5-FU) chemoresistance development.

Among the 152,810 estimated new cases of adenocarcinoma of the colon (COAD) and the rectum (READ) in 2024, the rates of colorectal cancer (CRC) are increasing in young adults (age < 55 years) [...].

Colorectal proliferative lesions are not common in dogs. However, recently we have observed an increase in the number of diagnosed cases and a lack of publications providing current epidemiological data on lesions of the large intestine in dogs. The aim of this study was a retrospective analysis of 217 canine colorectal non-neoplastic and neoplastic nodular lesions, and assessment of the frequency of occurrence of individual lesions and whether there is a risk of their occurrence depending on age, sex, or dog breed.

Half of the cases (52.5%) were malignant tumours with a significant predominance of adenocarcinoma (42.9%). In the group of malignant non-epithelial lesions, lymphoma and sarcomas predominated (4.1% and 4.1%, respectively) followed by three cases of plasmacytoma. Benign neoplastic tumours constituted almost one-third of all cases (26.7%) with obvious dominance of adenoma (24.0%). Benign mesenchymal tumours were represented only by leiomyoma (2.8%). The non-neoplastic lesions were represented by a heterogeneous group of polyps (20.3%) with a slight advantage of hyperplastic type (9.7%) and less numerous inflammatory, fibroblastic, lymphoid, and hamartomatous polyps. One case of ganglioneuromatosis in hamartomatous polyp was diagnosed. The vast majority of lesions, both non-neoplastic and neoplastic, were found in the rectum. French Bulldogs were the most numerous breeds in our study, especially among adenomas. Furthermore, benign tumours were diagnosed in younger animals than malignant tumours.

The results of our research provided new data expanding knowledge about the epidemiology of colorectal neoplastic and non-neoplastic proliferative lesions in dogs. Our results indicate that the majority of colorectal proliferative lesions in dogs are malignant, which is alarming. French Bulldogs could possibly be predisposed to proliferative lesions of the large intestine, and this predisposition was statistically confirmed in adenomas. Moreover, benign tumours may occur in animals as young as 1-2 years old.

Whether HCV infection is associated with colorectal cancer (CRC) development remains inconclusive.

A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database was conducted.

From 2003 to 2012, 1:2:2 propensity score-matched HCV-treated [interferon-based therapy ≥ 6 months, surveys for CRC (n = 9017), colon cancer (CC) (n = 9,022) and rectal cancer (RC) (n = 9,033), HCV-untreated and HCV-uninfected cohorts CRC (n = 18034), CC (n = 18,044) and RC (n = 18,066) were enrolled. The HCV-uninfected cohort had the lowest cumulative incidence of CRC (0.117%; 95% CI: 0.062%-0.207%), whereas the HCV-treated (0.966%; 0.375-2.122%) and HCV-untreated (0.807%; 0.485%-1.280%) cohorts had similar incidences (P = .0662); HCV infection [reference: HCV-untreated cohort, HCV-treated: hazard ratio (HR): 0.598; 95% CI HR: 0.337-1.059; HCV-uninfected: 0.250; 0.138-0.456] and age ≥ 49 years (3.128;1.751-5.59) were associated with CRC development. The HCV-untreated cohort had the highest cumulative incidence of CC (0.883%; 0.371-1.839%), while HCV-treated (0.478%; 0.110-1.518%) and HCV-uninfected cohorts (0.147%; 0.071-0.284%) had similar incidences (P = .4853); HCV infection (HCV-treated: 0.474; 0.232-0.971; HCV-uninfected: 0.338; 0.184-0.62), male sex (2.18; 1.301-3.654), age≥ 49 years (4.818; 2.123-10.936) and diabetes (1.983; 1.205-3.262) were associated with CC development. A higher RC cumulative incidence was noted in the HCV-untreated cohort (0.332%; 0.151-0.664%) than in the HCV-uninfected cohort (0.116%; 0.054-0.232%) (P = .0352); HCV infection (HCV-treated: 0.691; 0.295-1.617; HCV-uninfected: 0.424; 0.207-0.867), age ≥ 49 years (3.745, 1.576-8.898) and stroke (3.162; 1.366-7.322) were associated with RC development.

The baseline associations were HCV infection and age ≥ 49 years with CRC; male sex and diabetes with CC; and stroke with RC. Anti-HCV therapy might reverse the risk of HCV-related CC but not RC.

Background: A strong body of evidence exists demonstrating deleterious relationships between abnormal body composition (BC) and outcomes in non-complex colorectal cancer. Complex rectal cancer (RC) includes locally advanced and locally recurrent tumours. This scoping review aims to summarise the current evidence examining BC in complex RC. Methods: A literature search was performed on Ovid MEDLINE, EMBASE, and Cochrane databases. Original studies examining BC in adult patients with complex RC were included. Two authors undertook screening and full-text reviews. Results: Thirty-five studies were included. Muscle quantity was the most commonly studied BC metric, with sarcopenia appearing to predict mortality, recurrence, neoadjuvant therapy outcomes, and postoperative complications. In particular, 10 studies examined relationships between BC and neoadjuvant therapy response, with six showing a significant association with sarcopenia. Only one study examined interventions for improving BC in patients with complex RC, and only one study specifically examined patients undergoing pelvic exenteration. Marked variation was also observed in terms of how BC was quantified, both in terms of anatomical location and how cut-off values were defined. Conclusions: Sarcopenia appears to predict mortality and recurrence in complex RC. An opportunity exists for a meta-analysis examining poorer BC and neoadjuvant therapy outcomes. There is a paucity of studies examining interventions for poor BC. Further research examining BC specifically in patients undergoing pelvic exenteration surgery is also lacking. Pitfalls identified include variances in how BC is measured on computed tomography and whether external cut-off values for muscle and adipose tissue are appropriate for a particular study population.

Low-density lipoprotein cholesterol (LDL) is associated with the occurrence of colorectal cancer (CRC). This study aims to investigate its prognostic role and associated clinicopathological factors in the metastatic setting.

Patients with newly diagnosed synchronous metastatic CRC were included. Patients were grouped according to the serum LDL levels at the diagnosis (≤ 130 mg/dL: Normal-LDL, > 130 mg/dL: High-LDL). LDL-associated clinicopathological factors, progression-free survival (PFS), and overall survival (OS) were assessed.

A total of 90 patients were included. 44.4% (n = 40) was in the normal-LDL and 56.6% (n = 50) in the high-LDL group. Colonic localization of the primary tumor was more frequent in the high-LDL group (90% vs. 67.5%, p = 0.009). The high-LDL group more frequently had local treatments [metastasectomy (26% vs. 2.5%, p = 0.002) and embolization-ablation (38% vs. 17.5%, p = 0.033)]. Despite higher curative intent with local treatments in the high-LDL group, PFS [10.03 months (95% Confidence Interval (CI):6.97-14.77) vs 9.63 mo. (95% CI: 7.93-14.00), p = 0.872] and OS [20.87 mo. (95% CI: 14.87-36.47) vs. 17.63 mo. (95% CI: 14.30-43.03), p = 0.925] did not differ from the normal-LDL. Among patients treated without any curative intent, high LDL was associated with significantly worse PFS [4.97 mo. (95% CI: 3.00-7.73) vs. 8.43 mo. (95% CI: 6.10-9.90), p = 0.048].

This study suggests that serum LDL is associated with colonic primary localization in synchronous metastatic CRC. Levels > 130 mg/dL at diagnosis may be associated with worse survival and may be further investigated as a biomarker. Larger, multicenter and prospective studies are needed.

Verifying patients' position and internal anatomical changes are important steps in the radiotherapy of rectal cancer. Cone Beam Computed Tomography (CBCT) is an advanced imaging method that allows for the quantification of these modifications, ensuring the delivery of radiation dose to the tumor volume, while protecting surrounding organs at risk. The aim of this review is to discuss and analyze the benefits offered by this method of imaging on board the linear accelerator. In view of this, a systematic search of the scientific literature in the Medline/PubMed database was performed for publications over the last decade, with 20 articles found to be relevant for this study. To highlight the benefits of this imaging technique in rectal cancer, the frequency of CBCT use, identification of tumor volume and organs at risk on CBCT images, quantification of the movement of these organs and tumor volume, analysis of positioning errors as well as evaluation of dosimetric parameters were analyzed.

Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States, with recurrence being a frequent cause of mortality. Approaches to improve disease-free survival (DFS) are urgently needed. The gut microbiome, reflected in fecal samples, is likely mechanistically linked to CRC progression and may serve as a non-invasive biomarker. Accordingly, we leveraged baseline fecal samples from N = 166 stage I-III CRC patients in the ColoCare Study, a prospective cohort of newly diagnosed CRC patients. We sequenced the V3 and V4 regions of the 16S rRNA gene to characterize fecal bacteria. We calculated estimates of alpha diversity, beta diversity, and a priori- and exploratory-selected bacterial presence/absence and relative abundance. Associations of microbial metrics with DFS were estimated using multivariable Cox proportional hazards models. We found that alpha diversity was strongly associated with improved DFS, most strongly among rectal cancer patients (Shannon HRrectum = 0.40 95% CI = 0.19, 0.87; p = .02). Overall microbiome composition differences (beta diversity), as characterized by principal coordinate axes, were statistically significantly associated with DFS. Peptostreptococcus was statistically significantly associated with worse DFS (HR = 1.62, 95% CI = 1.13, 2.31; p = .01 per 1-SD) and Order Clostridiales was associated with improved DFS (HR = 0.62, 95% CI = 0.43-0.88; p = .01 per 1-SD). In exploratory analyses, Coprococcus and Roseburia were strongly associated with improved DFS. Overall, higher bacterial diversity and multiple bacteria were strongly associated with DFS. Metagenomic sequencing to elucidate species, gene, and functional level details among larger, diverse patient populations are critically needed to support the microbiome as a biomarker of CRC outcomes.

Rectal cancer accounts for over 35% of the worldwide colorectal cancer burden representing a distinctive subset of cancers from those arising in the colon. Colorectal cancers exhibit a continuum of traits that differ with their location in the large intestine. Due to anatomical and molecular differences, rectal cancer is treated differently from colon cancer, with neoadjuvant chemoradiotherapy playing a pivotal role in the control of the locally advanced disease. However, radioresistance remains a major obstacle often correlated with poor prognosis. Multifunctional nanomedicines offer a promising approach to improve radiotherapy response rates, as well as to increase the intratumoral concentration of chemotherapeutic agents, such as 5-Fluorouracil. Here, we revise the main molecular differences between rectal and colon tumors, exploring the complex orchestration beyond rectal cancer radioresistance and the most promising nanomedicines reported in the literature to improve neoadjuvant therapy response rates.

Type II diabetes mellitus (T2DM) has been associated with increased risk of colon cancer (CC) and worse prognosis in patients with metastases. The effects of T2DM on postoperative chemoresistance rate (CRR) and long-term disease-free survival (DFS) and overall survival (OS) in patients with stage III CC who receive curative resection remain controversial.

To investigate whether T2DM or glycemic control is associated with worse postoperative survival outcomes in stage III CC.

This retrospective cohort study included 278 patients aged 40-75 years who underwent surgery for stage III CC from 2018 to 2021. Based on preoperative T2DM history, the patients were categorized into non-DM (n = 160) and DM groups (n = 118). The latter was further divided into well-controlled (n = 73) and poorly controlled (n = 45) groups depending on the status of glycemic control. DFS, OS, and CRR were compared between the groups and Cox regression analysis was used to identify risk factors.

Patients in the DM and non-DM groups demonstrated similar DFS, OS, and CRR (DFS: 72.03% vs 78.75%, P = 0.178; OS: 81.36% vs 83.12%, P = 0.638; CRR: 14.41% vs 7.5%, P = 0.063). Poorly controlled DM was associated with a significantly worse prognosis and higher CRR than well-controlled DM (DFS: 62.22% vs 78.07%, P = 0.021; OS: 71.11% vs 87.67%, P = 0.011; CRR: 24.40% vs 8.22%, P = 0.015). High preoperative fasting plasma glucose [DFS: Hazard ratio (HR) = 2.684, P < 0.001; OS: HR = 2.105, P = 0.019; CRR: HR = 2.214, P = 0.005] and glycosylated hemoglobin levels (DFS: HR = 2.344, P = 0.006; OS: HR = 2.119, P = 0.021; CRR: HR = 2.449, P = 0.009) indicated significantly poor prognosis and high CRR, while T2DM history did not (DFS: HR = 1.178, P = 0.327; OS: HR = 0.933, P = 0.739; CRR: HR = 0.997, P = 0.581).

Increased preoperative fasting plasma glucose and glycosylated hemoglobin levels, but not T2DM history, were identified as risk factors associated with poor postoperative outcomes and high CRR in patients with stage III CC.

In 2022, colorectal cancer (CCR) had the second-highest incidence in Europe, preceded only by breast cancer [...].

To improve local disease control, the use of preoperative radiotherapy either alone or combined with chemotherapy has become standard practice in rectal cancer, but it is unclear how these treatments modify the antitumoral immune response. We aimed to evaluate tumor histopathologic features and the prognostic effect of host immune response in rectal cancer with variable treatment modalities. Ninety-five rectal cancers with short-course radiotherapy (SRT), 97 with long-course chemoradiotherapy (CRT), and 154 without preoperative treatments, were evaluated for histopathologic features including Crohn's-like reaction (CLR). CD3+ and CD8+ immunohistochemistry and tumor cells were analyzed from tumor tissue microarray samples to calculate T-cell densities and G-cross function values to estimate cancer cell-T-cell co-localization (proximity score). We found that lymphocyte densities were diminished after SRT, but CLR was scarcer after CRT. Proximity score and CLR density were prognostic for survival in cancer without preoperative treatments and could be combined into an enhanced prognostic score (immune grade). In the irradiated tumors, CLR density remained prognostic while the impact of T-cell infiltration was insufficient alone. In multivariable analysis, the immune grade proved to be an independent prognostic factor for survival. In conclusion, the immune contexture of rectal cancer harbors prognostic significance even after preoperative radiotherapy.

This study aims to investigate the correlation between the chondroitin sulfate proteoglycan 4 pseudogene 12 (CSPG4P12) polymorphism and the risk of colorectal cancer (CRC). This case-control study involved 850 patients with CRC and 850 health controls. The genotypes of CSPG4P12 (rs2880765, rs6496932, and rs8040855) were determined by the TaqMan-MGB probe method. Logistic regression model was employed to evaluate the association of CSPG4P12 single-nucleotide polymorphisms (SNPs) with the risk of CRC by calculating the odds ratio (OR) and 95% confidence interval (CI). The CSPG4P12 exhibited lower expression in CRC tissues. Our data showed that the rs6496932 variant increased CRC risk (CA vs. CC: p = 0.006; CA + AA vs. CC: p = 0.005). In contrast, the rs8040855 variant reduced the risk of CRC (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001). Stratification by gender and age revealed that the rs8040855 variant decreased CRC risk; however, the rs6496932 variant increased CRC risk among males (CA vs. CC: p = 0.024; CA + AA vs. CC: p = 0.014) and younger individuals (CA vs. CC: p = 0.004; CA + AA vs. CC: p = 0.010). When stratified by smoking and drinking status, the rs8040855 variant decreased CRC risk among nonsmokers (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001) and nondrinkers (CA vs. CC: p = 0.002; CA + AA vs. CC: p = 0.004). The rs6496932 variant increased CRC risk among nonsmokers (CA vs. CC: p = 0.016; CA + AA vs. CC: p = 0.036) and nondrinkers (CG vs. CC: p < 0.001; CG + GG vs. CC: p < 0.001). Haplotype analysis showed that the CSPG4P12 Trs2880765Crs6496932Grs8040855 haplotype reduced the risk of CRC compared with the reference haplotype (CSPG4P12 Ars2880765Crs6496932Crs8040855) (OR = 0.46, 95% CI = 0.26-0.82, p = 0.049). These findings highlight the potential of these genetic variants as biomarkers for CRC susceptibility, offering insights into personalized prevention strategies.

Early-onset colorectal cancer (EOCRC), recognized as a distinct subgroup with an increased incidence over the past two decades, characterized by its aggressive nature and potentially unique molecular factors that differentiate it from traditional colorectal cancer (CRC). In this study, we investigated differentially expressed genes in a young-CRC patient using paired-end mRNA-sequencing. Validation of target genes through qRT-PCR highlighted a significant increase in SERPINA3 levels in EOCRC, representing a novel finding. Epithelial expression of SERPINA3 demonstrated a strong association with disease progression, whereas stromal expression showed a negative correlation. Our findings reveal the distinct expression patterns and potential involvement of SERPINA3 in both the initiation and progression of CRC, suggesting that SERPINA3 could serve as a marker for distinguishing early-onset from late-onset cases.

This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: Primary objectives To identify and estimate the prognostic value of molecular biomarkers as predictors of pathological complete response to neoadjuvant chemoradiotherapy in people with locally advanced rectal cancer. summarises the review question in population, index prognostic factor, comparator prognostic factor(s), outcome, timing, and setting (PICOTS) format. [Table: see text] [Figure: see text] Secondary objectives To explore the following biomarker measurement, treatment, and study design factors as possible sources of heterogeneity in the association between the prognostic factor and pathological response: type of assay/measurement method, biomarker positivity criteria or cut-off point, chemotherapy regimen, and radiotherapy regimen.

The incidence of colorectal cancer (CRC) is increasing in the population under 50 years of age, with more than 10% of cases occurring in young adults. Fertility preservation counseling has therefore received increased attention in this younger patient population. The treatment of CRC is often based on multimodal therapies, including surgery, radiotherapy, chemotherapy, and, more recently, immunotherapy, which makes it difficult to estimate the expected effect of treatment on fertility. We, therefore, systematically analyzed the published literature on the gonadotoxic effects of CRC treatments to better advise patients on the risk of infertility and the need for fertility preservation measures. This systematic review and meta-analysis are part of the FertiTOX project, which aims to reduce the data gap regarding the gonadotoxicity of oncological therapies.

The aim of this review and meta-analysis is to evaluate the potential impact of CRC therapies on gonadal function to allow more accurate counseling regarding the risk of clinically relevant gonadotoxicity and the need for fertility preservation measures before oncological treatment.

A systematic literature search was conducted in Medline, Embase, the Cochrane database of systematic reviews, and CENTRAL in March 2024. A total of 22 out of 4420 studies were included in the review. Outcomes were defined as clinically relevant gonadotoxicity, indicated by elevated follicle-stimulating hormone (FSH) and/or undetectable anti-Müllerian hormone (AMH) levels and/or the need for hormone replacement therapy in women and azoo-/oligozoospermia and/or low inhibin B levels in men. Studies with fewer than nine patients were excluded from the meta-analysis.

The qualitative analysis included 22 studies with 1634 subjects (775 women, 859 men). Treatment consisted of active surveillance after surgery (37.7%), chemotherapy (12.7%), radiation (0.2%), or radiochemotherapy (53.9%). In 0.5%, the therapy was not clearly described. The meta-analysis included ten studies and showed an overall prevalence of clinically relevant gonadotoxicity of 23% (95% CI: 13-37%). In women, the prevalence was 27% (95% CI: 11-54%), and in men, 18% (95% CI: 13-26%). A subanalysis by type of CRC was only possible for rectal cancer, with a prevalence of relevant gonadotoxicity of 39% (95% CI: 20-64%). In patients undergoing chemotherapy exclusively, the prevalence was 4% (95% CI: 2-10%). In those receiving only radiotherapy, the prevalence was 23% (95% CI: 10-44%); in contrast, it reached 68% (95% CI: 40-87%) in patients who received radiochemotherapy.

This first meta-analysis of the clinically relevant gonadotoxicity of CRC therapies provides a basis for counseling on the risk of infertility and the need for fertility preservation measures. Despite the low prevalence of gonadotoxicity in cases receiving chemotherapy alone, fertility preservation is still recommended due to the uncertainty of subsequent therapy and the lack of large longitudinal data on individual treatment effects. Further prospective studies are needed to investigate the impact of CRC treatment on gonadal function and estimate the effect of new treatment modalities, such as immunotherapies.

Although charge-converting nanoparticles (NPs) potentially penetrate tumours deeply, conventional charge conversion strategies possess limitations, including low selectivity and slow, inconsistent conversion rate within the tumour microenvironment. In this study, we synthesized a zwitterionic near-infrared cyclodextrin derivative of heptamethine cyanine and complexed it with pheophorbide-conjugated ferrocene to produce multifunctional theranostic nanotherapeutics. Our NPs demonstrated enhanced tumour-targeting ability, enabling the highly specific imaging of rectal tumours, with tumour-to-rectum signal ratios reaching up to 7.8. The zwitterionic surface charge of the NPs was rapidly converted to a cationic charge within the tumours on 880 nm near-infrared laser irradiation, promoting the tumoural penetration of NPs via transcytosis. After penetration, photodynamic/chemodynamic therapy was initiated using a 660 nm laser. Our NPs eradicated clinically relevant-sized heterotopic tumours (~250 mm3) and orthotopic rectal tumours, displaying their potential as theranostic nanoplatforms for targeting rectal cancer.

Diesel exhaust exposure and cancer other than the lungs have been limitedly investigated.

To conduct a systematic review and meta-analysis on the association between occupational exposure to diesel exhaust and gastrointestinal cancers.

Two researchers performed a systematic literature review to identify all cohort studies on occupational exposure to diesel exhaust and risk of cancers other than lung. Of the 30 retained studies, 10 reported risk estimates for oesophageal, 18 on gastric, 15 on colon and 14 on rectal cancer. We performed random-effects meta-analyses to calculate summary relative risks (RRs) and 95% confidence intervals (CIs) for ever-exposure to diesel exhaust.

We calculated summary RR = 1.08 (95% CI 0.97-1.21, P heterogeneity = 0.06) for oesophageal, 1.06 (95% CI 0.99-1.14, P < 0.001) for gastric, 0.98 (95% CI 0.96-1.00, P = 0.453) for colon, and RR = 1.04 (95% CI 0.97-1.11, P = 0.013) for rectal cancer. Drivers showed an association with oesophageal (RR = 1.26, 95% CI 0.99-1.62), gastric (RR = 1.20, 95% CI 0.91-1.59) and rectal cancer (RR = 1.41, 95% CI 1.13-1.75); machine operators with oesophageal (RR = 1.09, 95% CI 1.00-1.20) and gastric (RR = 1.15, 95% CI 1.10-1.20) and handlers with oesophageal cancer (RR = 1.95, 95% CI 1.23-3.09). Studies from Europe revealed an association with gastric cancer while those from North America did not (P < 0.05). No difference was found by quality score except for gastric cancer, where high-quality studies but not low-quality ones showed increased risk (P heterogeneity = 0.04). There was no evidence of publication bias.

An increased but insignificant risk of oesophageal, gastric and rectal, but not colon cancer, was suggested in workers exposed to diesel exhaust. Residual confounding cannot be excluded.

Physical activity reduces colorectal cancer risk, yet the diurnal timing of physical activity in colorectal cancer etiology remains unclear.

This study used 24-h accelerometry time series from UK Biobank participants aged 42 to 79 years to derive circadian physical activity patterns using functional principal component analysis. Multivariable Cox proportional hazard models were used to examine associations with colorectal cancer risk.

Among 86,252 participants (56% women), 529 colorectal cancer cases occurred during a median 5.3-year follow-up. We identified four physical activity patterns that explained almost 100% of the data variability during the day. A pattern of continuous day-long activity was inversely associated with colorectal cancer risk (hazard ratio (HR) = 0.94, 95% confidence interval (CI) = 0.89-0.99). A second pattern of late-day activity was suggestively inversely related to risk (HR = 0.93, 95% CI = 0.85-1.02). A third pattern of early- plus late-day activity was associated with decreased risk (HR = 0.89, 95% CI = 0.80-0.99). A fourth pattern of mid-day plus night-time activity showed no relation (HR = 1.02, 95% CI = 0.88-1.19). Our results were consistent across various sensitivity analyses, including the restriction to never smokers, the exclusion of the first 2 years of follow-up, and the adjustment for shift work.

A pattern of early- plus late-day activity is related to reduced colorectal cancer risk, beyond the benefits of overall activity. Further research is needed to confirm the role of activity timing in colorectal cancer prevention.

Rectal cancer accounts for approximately one-third of colorectal cancers, with over 340,000 deaths globally in 2022. Despite advancements in treatment, the five-year overall survival for locally advanced rectal cancer (LARC) remains at 74%, with significant morbidity. B7H3 (CD276), an immune checkpoint protein, plays a role in tumor progression and resistance to therapy, and correlates with poor prognosis in various cancers, including colorectal cancer. This study aims to evaluate the expression of B7H3 in LARC and its impact on overall complete response (oCR) rates to neoadjuvant therapy.

A retrospective study was conducted on 60 patients with LARC who received neoadjuvant chemoradiation (nCRT) followed by total mesorectal excision (TME). B7H3 expression was assessed using immunohistochemistry on surgical specimens. Expression levels were categorized as high or low based on a composite score, and their association with oCR rates was analyzed.

High B7H3 expression was observed in 60% of patients, with 73.5% showing expression in more than 50% of tumor cells. Patients who achieved oCR had significantly lower B7H3 expression compared to those with residual disease (p < 0.001). No nuclear expression of B7H3 was detected. No significant correlation was found between B7H3 expression and other clinicopathological variables, except for a higher likelihood of non-restorative surgery in patients with elevated B7H3 levels (p = 0.049). Mucinous adenocarcinoma had high expression of B7H3.

Elevated B7H3 expression is associated with reduced oCR rates in LARC, highlighting its potential role as a prognostic biomarker. Further studies with larger cohorts are warranted to validate these findings and explore B7H3-targeted therapies as a treatment strategy for LARC.

We previously demonstrated that intake of low-fat dairy, but not high-fat dairy, was associated with a decreased colorectal cancer (CRC) recurrence risk. These risks, however, may differ by sex, primary tumour location, and disease stage. Combining data from two similar prospective cohort studies of people with stage I-III CRC enabled these subgroup analyses. Participants completed a food frequency questionnaire at diagnosis (n = 2283). We examined associations between low- and high-fat dairy intake and recurrence risk using multivariable Cox proportional hazard models, stratified by sex, and primary tumour location (colon and rectum), and disease stage (I/II and III). Upper quartiles were compared to lower quartiles of intake, and recurrence was defined as a locoregional recurrence and/or metastasis. During a median follow-up of 5.0 years, 331 recurrences were detected. A higher intake of low-fat dairy was associated with a reduced risk of recurrence (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.43-0.83), which seemed more pronounced in men (HR: 0.51, 95% CI: 0.34-0.77) than in women (HR: 0.84, 95% CI: 0.47-1.49). A higher intake of high-fat dairy was associated with an increased risk of recurrence in participants with colon cancer (HR: 1.60, 95% CI: 1.03-2.50), but not rectal cancer (HR: 0.88, 95% CI: 0.54-1.45). No differences in associations were observed between strata of disease stage. Concluding, our findings imply that dietary advice regarding low-fat dairy intake may be especially important for men with CRC, and that dietary advice regarding high-fat dairy intake may be specifically important in people with colon cancer.

Long-term outcomes in patients undergoing emergency versus elective resection for colorectal cancer (CRC) remain controversial. This study aims to assess short- and long-term outcomes of emergency versus elective CRC surgery.

In this single-center retrospective cohort study, patients undergoing emergency or elective colonic resections for CRC from January 2013 to December 2017 were included. Primary outcome was long-term survival. As secondary outcomes, we sought to analyze potential differences on postoperative morbidity and concerning the oncological standard of surgical resection. The Kaplan-Meier curves and Cox proportional hazard model were used to compare survival between the groups.

Overall, 225 CRC patients were included. Of these 192 (85.3%) had an elective and 33 (14.7%) an emergency operation. Emergency indications were due to obstruction, perforation, or bleeding. Patients in the emergency group had higher ASA score (p = 0.023), higher Charlsson comorbidity index (CCI, p = 0.012), and were older than those in the elective group, with median age 70 (IQR 63-79) years and 78 (IQR 68-83) years, for elective and emergency, respectively (p = 0.020). No other preoperative differences were observed. Patients in the emergency group experienced significantly more major complications (12.1% vs. 3.6%, p = 0.037), more anastomotic leakage (12.1% vs. 1.6%, p = 0.001), need for reoperation (12.1% vs. 3.1%, p = 0.021), and postoperative mortality (2 patients vs. 0, p < 0.001). No differences in terms of final pathological stage, nor in accuracy of lymphadenectomy were observed. Overall survival was significantly worse in case of emergency operation, with estimated median 41 months vs. not reached in elective cases (p < 0.001). At the multivariate analysis, emergency operation was confirmed as independent unfavorable determinant of survival (with hazard rate HR = 1.97, p = 0.028), together with age (HR = 1.05, p < 0.001), postoperative major morbidity (HR = 3.18, p = 0.012), advanced stage (HR = 5.85, p < 0.001), and need for transfusion (HR = 2.10, p = 0.049).

Postoperative morbidity and mortality were increased in emergency versus elective CRC resections. Despite no significant differences in terms of accuracy of resection and pathological stages, overall survival was significantly worse in patients who underwent emergency procedure, and independent of other determinants of survival.

Glioma-associated oncogene homolog-1 (GLI1) is amplified in human glioblastoma, and there is growing evidence suggesting its significant role in tumor development and metastasis. Our aim was to investigate the role of the GLI-1 gene in the progression of colorectal cancer (CRC) and its correlation with various clinicopathological features. Additionally, we examined the impact of the GLI-1 gene and other factors on the prognosis of CRC.

We analyzed a total of 98 confirmed CRC cases and adjacent normal tissue controls. Patients suspected of having colon cancer underwent a colonoscopy and targeted biopsy, while those with rectal cancer underwent CT scans and MRI. GLI1 expression was detected using real-time PCR assay, Western blotting, and immunohistochemistry.

The GLI1 gene was observed to be overexpressed in tumor tissues at both the protein and mRNA levels (p < 0.05). In addition, GLI1 overexpression was significantly associated with various factors such as tumor invasion (T3/T4), presence of lymph nodes, lymph node metastasis (LNM), stage (III/IV), tumor site (colon), tumor size (≥ 3 cm), localization (nucleocytoplasmic), strong staining intensity and recurrence (p < 0.05). The results of survival analysis showed that the patients with overexpression of GLI1 had a significantly lower DFS rate which was 21 months compared to those with normal expression who had 31 months (p < 0.05). Moreover, individuals with early onset disease (15 months) were more likely to have cytoplasmic localization of the GLI1 gene as opposed to nucleo-cytoplasmic localization of GLI1 which presented late-onset disease( 23 months) (p < 0.05). Finally, Stage and PNI (p < 0.05) were found to independently affect outcomes of CRC according to Cox regression analysis.

High expression of GLI-1 in CRC is associated with adverse pathology and poor prognosis for patients. The correlation between cytoplasmic localization of GLI-1 and reduced disease-free survival holds potential for guiding prognosis and treatment. Further research is needed to develop strategies targeting GLI-1 for improved outcomes.

Background: Colorectal cancer (CRC) is a gastrointestinal disease linked with GIT microbial dysbiosis. The present study has targeted the comparative analysis of virulent factor FadA from gut-associated bacteria of CRC patients (F. nucleatum) and healthy individuals (E. cloacae). Methods: For this purpose, FadA protein sequences of fifteen strains of F. nucleatum and four strains of E. cloacae, were retrieved from the UniProt database. These sequences were analysed through VirulentPred, PSLpred, ProtParam, PFP-FunDSeqE, PROTEUS Structure Prediction Server, SWISS-MODEL, SAVES validation server, MEME suite 5.5.0, CAVER Web tool, Webserver VaxinPAD, HPEPDOCK and HDOCK servers. Results: FadA protein from F. nucleatum was found to exhibit significant differences as compared to E. nucleatum i.e. it exhibited helical configuration, cytoplasmic, periplasmic, outer-membrane and extracellular localisation, 2D structure comprising of 70-96% helix, 0% beta-sheet, 4-30% coils and 17-20 signal peptide residues, hydrophilicity, strongly acidic character and smaller number of antigenic epitopes. In contrast, FadA protein from E. nucleatum was found to have globular 3D configuration, cytoplasmic localisation, 2D structure (30-56% helix, 12-21% beta-sheet, 33-50% coils and 43 signal peptide residues), highly hydrophobic, slightly acidic and more number of antigenic epitopes. Docking analyses of virulent factors revealed their high binding affinities with previously reported inhibitory peptide and FAD-approved drug COX2. Conclusion: The wide range of differences not only provided us the reason for the role of FadA protein as a virulent factor in F. nucleatum but also might help us in designing virulent FadA protein inhibiting strategies including peptide-based vaccine adjuvants and drugs designing, modification of tunnels and catalytic pockets to reduce substrate binding and FAD approved drugs selection. Inhibition of this virulent factor in CRC patients' gut bacteria might result in oncogenesis regression and reduced death rate.

β-site amyloid precursor protein (APP) cleaving enzyme 2 (BACE2) cleaves APP which is ubiquitously expressed in a variety of cell types including cancer cells. BACE2 can process APP in several ways and appears to be involved in the pathogenesis of cancer. Our purpose was to assess the association of mRNA expression and genetic polymorphism of BACE2 in colorectal cancer (CRC) susceptibility and its association to clinicopathological factors in Swedish patients with CRC.

A total of 720 CRC patients and 470 healthy controls were genotyped for BACE2 gene polymorphism rs2012050, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction. Reverse transcription quantitative PCR was used to investigate the BACE2 gene expression in 192 CRC tissue and 181 paired normal tissue.

Assessing clinicopathological factors, we noted that carrying of T allele in C/T and C/T+T/T was significantly associated with a protective role against disseminated cancer and higher lymph node status. Moreover, individuals carrying T/T genotype were significantly more likely to have poorly differentiated cancer. Follow-up data for patients in poorly differentiated cancer and the Kaplan-Meier analysis showed that the cancer-specific survival curves differed between C/C and C/T+T/T for the BACE2 gene polymorphism and that the carriers of the genotype C/C were associated with more favorable prognosis. We found no significant differences in the genotypic frequencies between the patients and healthy controls. BACE2 mRNA level was significantly 2.2-fold upregulated in CRC tissue when compared to noncancerous tissue. A higher BACE2 mRNA level was observed in smaller tumors and in rectal cancer when compared to colon cancer.

In patients with CRC, our results indicate BACE2 rs2012050 as a useful potential predictor of poor differentiation, disseminated cancer and lymph node status and that the BACE2 mRNA expression is associated to tumor size and cancer location.

LARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection.

Sequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome.

Our study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer.

Our study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance.

Gut bacterial dysbiosis has been linked to several gastrointestinal diseases, including deadly colorectal cancer (CRC), a leading cause of mortality in cancer patients. However, perturbation in gut bacteriome during colon cancer (CC, devoid of colorectal malignancy) remains poorly explored. Here, 16S rRNA gene amplicon sequencing was carried out for fecal DNA samples targeted to hypervariable V3-V4 region by employing MiSeq platform to explore the gut bacterial community shift in CC patients. While alpha diversity indices predicted high species richness and diversity, beta diversity showed marked gut bacterial compositional dissimilarity in CC versus healthy controls (HC, n = 10 each). We observed a significant (p < 0.05, Wilcoxon Rank-Sum test) emergence of low-abundant anaerobic taxa, including Parvimonas and Peptostreptococcus, in addition to Subdoligranulum, Coprococcus, Holdemanella, Solobacterium, Bilophila, Blautia, Dorea, Moryella and several unidentified taxa, mainly affiliated to Firmicutes, in CC patients. In addition, we also traced the emergence of putative probiotic taxon Slackia, belonging to Actinomycetota, in CC patients. The emergence of anaerobic Firmicutes in CC is accompanied by a significant (p < 0.05) decline in the Klebsiella, as determined through linear discriminant analysis effect size (LEfSe) and heat tree analyses. Shifts in core microbiome and variation in network correlation were also witnessed. Taken together, this study highlighted a significant and consistent emergence of rare anaerobic Firmicutes suggesting possible anaerobiosis driving gut microbial community shift, which could be exploited in designing diagnostic and therapeutic tools targeted to CC.

Estrogen is a group of hormones that collaborate with the nervous system to impact the overall well-being of all genders. It influences many processes, including those occurring in the central nervous system, affecting learning and memory, and playing roles in neurodegenerative diseases and mental disorders. The hormone's action is mediated by specific receptors. Significant roles of classical estrogen receptors, ERα and ERβ, in various diseases were known since many years, but after identifying a structurally and locationally distinct receptor, the G protein-coupled estrogen receptor (GPER), its role in human physiology and pathophysiology was investigated. This review compiles GPER-related information, highlighting its impact on homeostasis and diseases, while putting special attention on functions and dysfunctions of this receptor in neurobiology and biobehavioral processes. Understanding the receptor modulation possibilities is essential for therapy, as disruptions in receptors can lead to diseases or disorders, irrespective of correct estrogen levels. We conclude that studies on the GPER receptor have the potential to develop therapies that regulate estrogen and positively impact human health.

Copper-mediated cell death presents distinct pathways from established apoptosis processes, suggesting alternative therapeutic approaches for colon cancer. Our research aims to develop a predictive framework utilizing long-noncoding RNAs (lncRNAs) related to cuproptosis to predict colon cancer outcomes while examining immune interactions and intercellular signaling. We obtained colon cancer-related human mRNA expression profiles and clinical information from the Cancer Genome Atlas repository. To isolate lncRNAs involved in cuproptosis, we applied Cox proportional hazards modeling alongside the least absolute shrinkage and selection operator technique. We elucidated the underlying mechanisms by examining the tumor mutational burden, the extent of immune cell penetration, and intercellular communication dynamics. Based on the model, drugs were predicted and validated with cytological experiments. A 13 lncRNA-cuproptosis-associated risk model was constructed. Two colon cancer cell lines were used to validate the predicted representative mRNAs with high correlation coefficients with copper-induced cell death. Survival enhancement in the low-risk cohort was evidenced by the trends in Kaplan-Meier survival estimates. Analysis of immune cell infiltration suggested that survival was induced by the increased infiltration of naïve CD4+ T cells and a reduction of M2 macrophages within the low-risk faction. Decreased infiltration of naïve B cells, resting NK cells, and M0 macrophages was significantly associated with better overall survival. Combined single-cell analysis suggested that CCL5-ACKR1, CCL2-ACKR1, and CCL5-CCR1 pathways play key roles in mediating intercellular dialogues among immune constituents within the neoplastic microhabitat. We identified three drugs with a high sensitivity in the high-risk group. In summary, this discovery establishes the possibility of using 13 cuproptosis-associated lncRNAs as a risk model to assess the prognosis, unravel the immune mechanisms and cell communication, and improve treatment options, which may provide a new idea for treating colon cancer.

Conventional screening options for colorectal cancer (CRC) detection are mainly direct visualization and invasive methods including colonoscopy and flexible sigmoidoscopy, which must be performed in a clinical setting and may be linked to adverse effects for some patients. Non-invasive CRC diagnostic tests such as computed tomography colonography and stool tests are either too costly or less reliable than invasive ones. On the other hand, volatile organic compounds (VOCs) are potentially ideal non-invasive biomarkers for CRC detection and monitoring. The present review is a comprehensive presentation of the current state-of-the-art VOC-based CRC diagnostics, with a specific focus on recent advancements in biosensor design and application. Among them, breath-based chromatography pattern analysis and sampling techniques are overviewed, along with nanoparticle-based optical and electrochemical biosensor approaches. Limitations of the currently available technologies are also discussed with an outlook for improvement in combination with big data analytics and advanced instrumentation, as well as expanding the scope and specificity of CRC-related volatile biomarkers.

Matrix metalloproteinase 13 (MMP13) has been reported to be involved in tumor development and progression, including of colorectal cancer (CRC). This study aimed at evaluating whether the MMP13 rs2252070 gene polymorphism is associated with clinicopathological factors and its influence on long-term survival in Swedish patients with CRC.

A total of 723 patients with CRC were genotyped using TaqMan single nucleotide polymorphism assays based on polymerase chain reaction.

Assessing clinicopathological factors, we demonstrated that having the G/G genotype for MMP13 rs2252070 was significantly associated with poor differentiation, higher serum level of carcinoembryonic antigen and higher lymph node status. Moreover, the presence of a G allele was significantly related to larger tumor size in rectal cancer but had a significantly protective role against mucinous cancer, perineural invasion and lymphovascular invasion. Kaplan-Meier analysis showed no difference between genotypes regarding cancer-specific survival.

Our findings highlight the potential of MMP13 rs2252070 polymorphism as a useful predictor of poor differentiation, serum level of carcinoembryonic antigen, lymph node status, tumor size, mucinous cancer, perineural invasion and lymphovascular invasion in patients with CRC.

The NFκB pathway, known as the central regulator of inflammation, has a well-established role in colorectal cancer (CRC) initiation, progression, and therapy resistance. Due to the pathway's overarching roles in CRC, there have been efforts to characterise NFκB family members and target the pathway for therapeutic intervention. Initial research illustrated that the canonical NFκB pathway, driven by central kinase IKKβ, was a promising target for drug intervention. However, dose limiting toxicities and specificity concerns have resulted in failure of IKKβ inhibitors in clinical trials. The field has turned to look at targeting the less dominant kinase, IKKα, which along with NFκB inducing kinase (NIK), drives the lesser researched non-canonical NFκB pathway. However prognostic studies of the non-canonical pathway have produced conflicting results. There is emerging evidence that IKKα is involved in other signalling pathways, which lie outside of canonical and non-canonical NFκB signalling. Evidence suggests that some of these alternative pathways involve a truncated form of IKKα, and this may drive poor cancer-specific survival in CRC. This review aims to explore the multiple components of NFκB signalling, highlighting that NIK may be the central kinase for non-canonical NFκB signalling, and that IKKα is involved in novel pathways which promote CRC.

Historical external beam radiation therapy (EBRT) for rectosigmoid cancer (RCa) predisposed patients to an increased risk of secondary bladder cancer (BCa). However, no contemporary radiotherapy studies are available. We addressed this knowledge gap.

Within the Surveillance, Epidemiology, and End Results database (2000-2020), we identified non-metastatic RCa patients who either underwent radiotherapy (EBRT+) or did not (EBRT-). Cumulative incidence plots and multivariable competing risk regression models (CRR) were fitted to address rates of BCa after RCa. In the subgroup of BCa patients, the same methodology addressed BCa-specific mortality (BCSM) according to EBRT exposure status.

Of the 188,658 non-metastatic RCa patients, 54,562 (29%) were EBRT+ vs. 134,096 (73%) who were EBRT-. In the cumulative incidence plots, the ten-year BCa rates were 0.7% in EBRT+ vs. 0.7% in EBRT- patients (p = 0.8). In the CRR, EBRT+ status was unrelated to BCa rates (multivariable HR: 1.1, p = 0.8). In the subgroup of 1416 patients with BCa after RCa, 443 (31%) were EBRT+ vs. 973 (69%) who were EBRT-. In the cumulative incidence plots, the ten-year BCSM rates were 10.6% in EBRT+ vs. 12.1% in EBRT- patients (p = 0.7). In the CRR, EBRT+ status was unrelated to subsequent BCSM rates (multivariable HR: 0.9, p = 0.9).

Although historical EBRT for RCa predisposed patients to higher BCa rates, contemporary EBRT for RCa is not associated with increased subsequent BCa risk. Moreover, in patients with BCa after RCa, exposure to EBRT does not affect BCSM.

The ability to predict or detect colorectal cancer (CRC) recurrence early after surgery enables physicians to apply appropriate treatment plans and different follow-up strategies to improve patient survival. Overall, 30-50% of CRC patients experience cancer recurrence after radical surgery, but current surveillance tools have limitations in the precise and early detection of cancer recurrence. Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor and enter the bloodstream. These can provide real-time information on disease status. CTCs might become novel markers for predicting CRC recurrence and, more importantly, for making decisions about additional adjuvant chemotherapy. In this review, the clinical application of CTCs as a therapeutic marker for stage II CRC is described. It then discusses the utility of CTCs for monitoring cancer recurrence in advanced rectal cancer patients who undergo neoadjuvant chemoradiotherapy. Finally, it discusses the roles of CTC subtypes and CTCs combined with clinicopathological factors in establishing a multimarker model for predicting CRC recurrence.

Objectives: The COVID-19 pandemic and its associated restrictions have resulted in delayed diagnoses across various tumor entities, including rectal cancer. Our hypothesis was based on the expectation of a reduced number of primary operations due to higher tumor stages compared to the control group. Methods: In a single-center retrospective study conducted from 1 March 2018 to 1 March 2022, we analyzed 120 patients with an initial diagnosis of rectal cancer. Among them, 65 patients were part of the control group (pre-COVID-19), while 55 patients were included in the study group (during the COVID-19 pandemic). We compared tumor stages, treatment methods, and complications, presenting data as absolute numbers or mean values. Results: Fewer primary tumor resections during the COVID-19 pandemic (p = 0.010), as well as a significantly lower overall number of tumor resections (p = 0.025) were seen compared to the control group. Twenty percent of patients in the COVID-19 group received their diagnosis during lockdown periods. These patients presented significantly higher tumor stages (T4b: 27.3% vs. 6.2%, p = 0.025) compared to the control group prior to the pandemic. In addition, more patients with angiolymphatic invasion (ALI) were identified in the COVID-19 group following neoadjuvant treatment compared to the control group (p = 0.027). No differences were noted between the groups regarding complications, stoma placement, or conversion rates. Conclusions: The COVID-19 pandemic, particularly during lockdown, appears to have contributed to delayed diagnoses, resulting in higher tumor stages and a decreased number of surgeries. The quality of rectal cancer treatment can be maintained under pandemic conditions.

Metformin, utilized to manage hyperglycemia, has been linked to a reduced risk of colorectal cancer (CRC) among individuals with diabetes. However, evidence is lacking for non-Hispanic Black individuals and those with lower socioeconomic status (SES), who face elevated risk for both diabetes and CRC. In this study, we investigated the association between metformin use and incident CRC risk within the Southern Community Cohort Study (SCCS), a racially- and SES-diverse prospective cohort.

Participants reported their diabetes diagnosis and medications, including metformin, upon enrollment (2002-2009) and during follow-up surveys approximately every five years. Incident cases of CRC were identified through state cancer registries and the National Death Index. Proportional hazards models were employed to explore the relationship between metformin use and CRC risk, adjusted for cancer risk factors.

A total of 25,992 participants with diabetes were included in the analysis, among whom 10,095 were taking metformin. Of these participants, 76% identified as non-Hispanic Black, and 60% reported household incomes <$15,000/year. Metformin use was associated with a significantly lower CRC risk (HR [95% CI]: 0.71 [0.55-0.93]), with consistent results for both colon (0.80 [0.59-1.07]) and rectal cancers (0.49 [0.28-0.86]). The protective association appeared to be stronger among non-Hispanic White individuals (0.51 [0.31-0.85]) compared to non-Hispanic Black participants (0.80 [0.59-1.08], p-interaction =.13). Additionally, a protective association was observed among obese individuals (BMI ≥30 kg/m2, 0.59 [0.43-0.82] but not among non-obese participants (0.99 [0.65-1.51], p-interaction =.05) CONCLUSION: Our findings indicate that metformin use is associated with a reduced risk of CRC in individuals with diabetes, including among those from predominantly low SES backgrounds. These results support previous epidemiological findings, and demonstrate that the protective association for metformin in relation to incident CRC likely generalizes to populations with higher underlying risk.

Although colon (COAD) and rectal adenocarcinoma (READ) combined to refer to colorectal cancer (CRC), substantial clinical evidence urged that CRC should be treated as two different cancers due to compared with READ, COAD showed higher morbidity and worse 5-year survival.

This study has tried to screen for the crucial gene that caused the worse prognosis and investigate its mechanism for mediating tumor growth and metastases in COAD. Meanwhile, the potential anti-COAD compound implicated in this mechanism was identified and testified from 1,855 food-borne chemical kits. This study aims to bring a new perspective to the development of new anti-COAD drugs and personalized medicine for patients with COAD.

The survival-related hub genes in COAD and READ were screened out from The Cancer Genome Atlas (TCGA) database and the results showed that HIGD1A, lower expressed in COAD than in READ, was associated with poor prognosis in COAD patients, but not in READ. Over-expressed HIGD1A suppressed CRC cell proliferation, invasion, and migration in vitro and in vivo. Meanwhile, the different expressed microRNA profiles between COAD and READ showed that miR-501-3p was highly expressed in COAD and inhibited HIGD1A expression by targeting 3'UTR of HIGD1A. MiR-501-3p mimics promoted cell proliferation and metastasis in CRC cells. In addition, Procyanidin C1 (PCC1), a kind of natural polyphenol has been verified as a potential miR-501-3p inhibitor. In vitro and in vivo, PCC1 promoted HIGD1A expression by suppressing miR-501-3p and resulted in inhibited tumor growth and metastasis.

The present study verified that miR-501-3p/HIGD1A axis mediated tumor growth and metastasis in COAD. PCC1, a flavonoid that riched in food exerts anti-COAD effects by inhibiting miR-501-3p and results in the latter losing the ability to suppress HIGD1A expression. Subsequently, unfettered HIGD1A inhibited tumor growth and metastasis in COAD.