Aims/Background: This investigation sought to establish a possible correlation between thrombin measurement levels and the risk of developing colon adenocarcinoma (COAD). Methods: Thrombin measurement levels were sourced from a study by Pietzner M (2020, PMID: 33328453) and integrated into the IEU database. Data on COAD were obtained from the FinnGen database (2021, C3_COLON_ADENO). Various analytical methods were used to assess the relationship, including inverse variance weighting (IVW), mendelian randomization-Egger (MR-Egger) regression, as well as weighted median and mode techniques. Sensitivity analyses were performed, including Cochran\'s Q test, MR-Egger intercept test, mendelian randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), along with leave-one-out analysis, to ensure the robustness of the results. Results: The IVW analysis indicated a significant inverse association between elevated thrombin levels and the risk of COAD (odds ratio (OR) = 0.76, 95% CI = 0.66-0.88, p = 0.0003). These findings were supported by the weighted median analysis (OR = 0.78, 95% CI = 0.68-0.90, p = 0.0006) and the weighted mode analysis (OR = 0.78, 95% CI = 0.68-0.88, p = 0.0017). Conclusion: This research identified an inverse causal relationship between thrombin measurement levels and the incidence of COAD, suggesting that higher thrombin levels are associated with a reduced risk of developing COAD.

Colon adenocarcinoma (COAD) is the predominant type of colorectal cancer. Early diagnosis and treatment can significantly improve the prognosis of COAD patients. Anoctamin 7 (ANO7), an anion channel protein, has been implicated in prostate cancer and other types of cancer. In this study, we analyzed the expression of ANO7 and its correlation with clinicopathological characteristics among COAD patients using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and the University of Alabama at Birmingham CANcer (UALCAN) databases. The GEPIA2, Kaplan-Meier plotter, and the Survival Genie platform were employed for survival analysis. The co-expression network and potential function of ANO7 in COAD were analyzed using GeneFriends, the Database for Annotation, Visualization and Integrated Discovery (DAVID), GeneMANIA, and Pathway Studio. Our data analysis revealed a significant reduction in ANO7 expression levels within COAD tissues compared to normal tissues. Additionally, ANO7 expression was found to be associated with race and histological subtype. The COAD patients exhibiting low ANO7 expression had lower survival rates compared to those with high ANO7 expression. The genes correlated with ANO7 were significantly enriched in proteolysis and mucin type O-glycan biosynthesis pathway. Furthermore, ANO7 demonstrated a direct interaction and a positive co-expression correlation with mucin 2 (MUC2). In conclusion, our findings suggest that ANO7 might serve as a potential prognostic biomarker and potentially plays a role in proteolysis and mucin biosynthesis in the context of COAD.

BACKGROUND: The existence of amino acid metabolic reprogramming in tumor cells is well established. However, the potential correlation between blood amino acids and the risk of colon adenocarcinoma remains largely unexplored.
METHODS: We utilized Mendelian randomization (MR) analysis to examine the association between 20 amino acids in the blood and the risk of colon adenocarcinoma. Additionally, reverse MR analysis was employed to identify the presence of reverse causality. A two-step MR analysis was conducted to ascertain the potential mediating effect. Lastly, the alanine detection data from colon adenocarcinoma patients in our hospital were utilized to investigate the differences in alanine levels among healthy individuals and patients with colon cancer, as well as among patients with different stages and locations of colon cancer. Furthermore, a Kaplan-Meier curve was employed to examine the correlation between alanine and overall survival, followed by the implementation of COX univariate analysis.
RESULTS: The results of our study indicate that there is an inverse correlation between alanine and the risk of colon adenocarcinoma. Additionally, we found no significant evidence to support a causal relationship between colon adenocarcinoma and alanine. Furthermore, our analysis revealed that alanine aminotransferase (ALT) and blood glucose do not act as mediators in this causal pathway. Moreover, individuals diagnosed with colon adenocarcinoma exhibited a significant decrease in alanine levels, particularly in cases of stage IV colon adenocarcinoma with distant metastasis. Additionally, elevated alanine levels were associated with improved overall survival rates among colon adenocarcinoma patients.
CONCLUSIONS: The results of this study indicate that alanine exhibits protective characteristics against the onset of colon adenocarcinoma and may play a role in promoting a more favorable disease prognosis. Consequently, dietary interventions aimed at increasing alanine intake may serve as a potential strategy for the prevention and treatment of colon adenocarcinoma.

The potential mechanism underlying the association between Homologous recombination deficiency (HRD) and immunotherapy in colon cancer has not been investigated.
The exon sequencing data and transcriptome data of 456 colon adenocarcinoma (COAD) patients were obtained from the TCGA database. Pathway activity score was calculated by GSVA methods and engaged in further survival analysis. The prognostic value of the candidate pathways was validated in an external GEO cohort and an immunotherapy cohort.
Patients with high HRD were associated with poor prognosis, lower tumor mutation burden and microsatellite instability, higher fraction genome alteration, and less sensitivity to immunotherapy in COAD. And then, the neuroactive ligand-receptor interaction pathway was over-activated in high-HRD tumors and associated with immunosuppression in colon cancer with high HRD. Besides, the pathway was associated with prognosis and immunotherapy response in COAD. Moreover, genes in this pathway such as LTB4R2 can be used as a novel target for therapy development in colon cancer.
Our study not only revealed the potential mechanism of HRD and the function of the neuroactive ligand-receptor interaction pathway in colon cancer but also provided new clues for the improvement of immunotherapy response in colon cancer.

OBJECTIVE: To evaluate DNA ploidy and S-phase fraction (SPF) in non-Lynch colonic adenocarcinoma, ulcerative colitis (UC), Crohn disease (CD) which are known as risk factors, and colitis. We correlated ploidy and SPF with tumor grading, staging and BRAF expression.
METHODS: All studied adenocarcinomas have intact mismatch repair genes as proved by immunohistochemistry. All were assessed for ploidy by automated image-based DNA cytometry and histograms were drawn. Immunostaining by anti-BRAF V600E was performed. Diagnostic laparoscopy (DL) was done as a preliminary step for staging GI cancers.
RESULTS: there is significant difference in DNA ploidy between groups; 77.5% and 17.5% of aneuploid cases are adenocarcinoma and UC. Groups are compared in terms of 2C, 4C, above 4C DNA content and SPF and significant difference is principally found between adenocarcinoma group and others. In adenocarcinomas, DNA ploidy is significantly correlated with tumor staging and grading. Regarding BRAF expression, there is significant difference between groups; all adenocarcinomas, 83.33% of UC were positive, while all cases of colitis, bilharzial colitis, CD were negative. There is significant relation between BRAF and SPF among all diploid cases including adenocarcinoma, and among non-neoplastic diploid cases. There is direct significant relation between BRAF intensity and adenocarcinoma staging. There is no significant difference between BRAF and ploidy among UC cases, although 75% of aneuploid UC are positive. DL helps in GI cancer staging. Routine laparoscopy before laparotomy, especially in cancers which have equivocal operability helps to avoid unnecessary laparotomies.
CONCLUSIONS: Based on significant difference in ploidy between adenocarcinoma and UC and between SPF and ploidy, assessment of ploidy by DNA cytometry for UC and other colitis could therefore predict impending malignant transformation before development of colonic dysplasia. Also measuring SPF in adenocarcinoma helps to select patients who could greatly benefit from chemotherapy. DL has vital role in staging GI cancers.

Opioid-induced immunomodulation may be important in colon adenocarcinoma, where tumour DNA mismatch repair (MMR) can determine the level of immune activation with consequences for therapeutic response and prognosis. We evaluated the relationship between intraoperative opioid exposure, MMR subtype, and oncological outcomes after surgery for colon adenocarcinoma.
Intraoperative opioid use (standardised by calculating morphine milligram equivalents) during stage I-III colon adenocarcinoma resection was reviewed retrospectively. Tumours were classified as DNA mismatch repair deficient (dMMR) or proficient (pMMR) by immunohistochemistry. The primary outcome was local tumour recurrence, distant tumour recurrence, or both (multivariable analysis). The exposures of interest were intraoperative analgesia and tumour subtype. Opioid-related gene expression was analysed using The Cancer Genome Atlas Colon Adenocarcinoma transcriptomic data.
Clinical and pathological data were analysed from 1157 subjects (median age, 60 [51-70] yr; 49% female) who underwent curative resection for stage I-III colon adenocarcinoma. Higher intraoperative opioid doses were associated with reduced risk of tumour recurrence (hazard ratio=0.92 per 10 morphine milligram equivalents; 95% confidence interval [95% CI], 0.87-0.98; P=0.007), but not with overall survival. In tumours deficient in DNA MMR, tumour recurrence was less likely (HR=0.38; 95% CI, 0.21-0.68; P=0.001), with higher opioid dose associated with eightfold lower recurrence rates. Gene expression related to opioid signalling was different between dMMR and pMMR tumours.
Higher intraoperative opioid dose was associated with a lower risk of tumour recurrence after surgery for stage I-III colon adenocarcinoma, but particularly so in tumours in which DNA MMR was deficient.

UNASSIGNED: Previous studies reported that dysregulation of RNA-binding proteins (RBPs) is significantly associated with the development of cancer. However, there are few studies to date on the role of RBPs in colon adenocarcinoma (COAD).
UNASSIGNED: RNA sequencing and clinical data for COAD patients were downloaded from The Cancer Genome Atlas (TCGA) database to identify differentially expressed (DE) RBPs between COAD tissue and normal colon tissue, and then the expression and prognostic significance of these RBPs were investigated in detail by systematic bioinformatics analysis. qRT-PCR was used to validate the expressions of prognosis-related RBP-encoding genes.
UNASSIGNED: Seven RBPs (RPL10L, ERI1, POP1, CAPRIN2, TDRD7, SNIP1 and PPARGC1A) were identified as hub genes associated with prognosis by a series of regression analyses, and were then used to construct a prognostic model. Further analysis based on this model indicated that the overall survival (OS) of the high-risk groups was lower than that of the low-risk groups. In this prognostic model, the area under the ROC curve (AUC) was 0.694, 0.709 and 0.665 for the TCGA cohort at 1, 3 and 5 years, respectively, while the AUC was 0.671, 0.633 and 0.601 for the GEO combined cohort at 1, 3 and 5 years, respectively, indicating the good predictive ability of the model. We also built a nomogram based on the 7 RBPs in the TCGA cohort, and the model showed good discriminatory ability for COAD.
UNASSIGNED: We screened seven prognosis-related genes in COAD patients based on RBP-related genes, validated the expressions of the seven prognosis-related RBP-encoding genes by qRT-PCR and constructed a prognosis-related nomogram for patients with COAD.

BACKGROUND: Visual information is crucial for performing laparoscopic surgery. While surgeons lose depth perception and spatial orientation in conventional 2D laparoscopy, the 4th generation 3D system gives a better depth perception.
OBJECTIVE: In this sstudy, we aimed to investigate the feasibility, safety, and short-term efficacy of 4th generation 3D-HD visualization technology applied in laparoscopic colon cancer surgery.
METHODS: One hundred and twenty patients with colon adenocarcinoma were recruited in this study. Patients were randomized on the day of surgery by a random computer-generated allocation list to undergo either a 3D-HD display or 2D-HD imaging system laparoscopic colon cancer surgery. In total, 60 patients underwent laparoscopic colon resection by 3D-HD laparoscope (3D group) and 60 patients underwent 2D-HD laparoscope (2D group). After the insertion of the access ports, both surgical procedures were divided in component tasks, and the execution times were compared. Data analysis was done using SPSS (version 15.0). Quantitative and qualitative variables were compared applying Student t test and Pearson\'s chi-square test.
RESULTS: Two groups were homogenous in terms of demographic data. Operation time was significantly shorter for the 3D group than for the 2D group (123.2±34.2 min vs. 142.2±23.5 min, P=0.018). There was no statistically significant difference between two groups in terms of intraoperative blood loss, the number of retrieved lymph nodes, postoperative recovery, and postoperative complications (P>0.05).
CONCLUSIONS: The 4th generation 3D-HD vision system reduced the operating time compared to 2D-HD vision system. It seems that use of the 3D-HD technology can significantly enhance the possibility of achieving better intraoperative results. 
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As a well-known herb used in the treatment of colon adenocarcinoma (COAD), Spica Prunellae (SP) shows favorable clinical effect and safety in China for many years, but its active ingredients and therapeutic mechanisms against COAD remain poorly understood. Therefore, this study aims to uncover active ingredients and mechanisms of SP in the treatment of COAD using a combined approach of network pharmacology and bioinformatics.
A comprehensive approach mainly comprised of target prediction, network construction, pathway and functional enrichment analysis, and hub genes verification was adopted in the current study.
We collected 102 compounds-related genes and 3549 differently expressed genes (DEGs) following treatment with SP, and 64 disease-drug target genes between them were recognized. In addition, a total of 25 active ingredients in SP were identified. Pathway and functional enrichment analyses suggested that the mechanisms of SP against COAD might be to induce apoptosis of colon cancer cells by regulating PI3K-Akt and TNF signaling pathways. Recognition of hub genes and core functional modules was performed by constructing protein-protein interaction (PPI) network, from which TP53, MYC, MAPK8 and CASP3 were found as the hub target genes that might play an important part in therapy for COAD. Subsequently we further compared the differential expression level and assessed the prognostic value of these four hub genes. These result of verification suggested that SP exerted therapeutic effects against COAD via a PPI network involving TP53, MYC, MAPK8 and CASP3.
In this study, active ingredients and mechanisms of SP in the treatment of COAD were systematically discussed, which provided the foundation for further experimental studies and might act to promote its appropriate clinical application.

Objective: We conducted this propensity score (PS)-matched, nationwide, population-based cohort study to estimate the effects of adjuvant oral or intravenous (IV) fluoropyrimidine in patients with high-risk stage II or III colon adenocarcinoma. Design: Using PS matching, we minimized the confounding effects on adjuvant oral or IV fluoropyrimidine outcomes in patients with high-risk stage II or III resectable colon adenocarcinoma. Setting: We selected patients from the Taiwan Cancer Registry database receiving adjuvant fluoropyrimidine monotherapy and divided them into those receiving IV fluoropyrimidine (IV group) and those receiving oral fluoropyrimidine (oral group). Results: In both univariate and multivariate Cox regression analyses, the adjusted hazard ratio (aHR) derived for the oral group was 1.34 (95% CI: 1.19-1.51) compared with the IV group. Moreover, in both univariate and multivariate analyses, aHR derived for significant independent prognostic risk factors for poor overall survival were male sex, age ≥ 60 years old, pathologic stage III, right-sided colon cancer, low income, and high Charlson comorbidity index. However, intergroup differences were not significant among female patients or patients < 60 years old on multivariate analysis, including no difference in overall survival. Conclusions: Adjuvant IV fluoropyrimidine is more suitable than adjuvant oral fluoropyrimidine for patients with stage II colon adenocarcinoma who have high-risk pathologic features or stage III colon adenocarcinoma.