Colon Cancer Outcomes Research Articles

A novel m7G-related miRNA prognostic signature for predicting clinical outcome and immune microenvironment in colon cancer.

Background: Colon cancer (CC) is a highly prevalent malignancy worldwide, characterized by elevated mortality rates and poor prognosis. N7-methylguanosine (m7G) methylation is an emerging RNA modification type and involved in the development of many tumors. Despite this, the correlation between m7G-related miRNAs and CC remains to be elucidated. This research aimed to investigate the clinical significance of m7G-related miRNAs in predicting both the prognosis and tumor microenvironment (TME) of CC. Method: We retrieved transcriptome data and associated clinical information from a publicly accessible database. Using univariate Cox and LASSO regression analyses, we established a signature of m7G-related miRNAs. Additionally, we used CIBERSORT and ssGSEA algorithms to explore the association between the prognostic risk score and the TME in CC patients. By considering the risk signature and immune infiltration, we identified differentially expressed genes that contribute to the prognosis of CC. Finally, the expression patterns of prognostic miRNAs were verified using quantitative reverse transcriptase PCR (qRT-PCR) in cell lines. Results: We constructed a prognostic risk signature based on seven m7G-related miRNAs (miR-136-5p, miR-6887-3p, miR-195-5p, miR-149-3p, miR-4433a-5p, miR-31-5p, and miR-129-2-3p). Subsequently, we observed remarkable differences in patient outcomes between the high- and low-risk groups. The area under the curve (AUC) for 1-, 3-, and 5-year survivals in the ROC curve were 0.735, 0.707, and 0.632, respectively. Furthermore, our results showed that the risk score can serve as an independent prognostic biomarker for overall survival prediction. In terms of immune analysis, the results revealed a significant association between the risk signature and immune infiltration, as well as immune checkpoint expression. Finally, our study showed that CCDC160 and RLN3 is the gene most relevant to immune cells and function in CC. Conclusion: Our study conducted a comprehensive and systematic analysis of m7G-associated miRNAs to construct prognostic profiles of CC. We developed a prognostic risk model based on m7G-miRNAs, with the resulting risk scores demonstrating considerable potential as prognostic biomarkers. These findings provide substantial evidence for the critical role of m7G-related miRNAs in colon cancer and may offer new immunotherapeutic targets for patients with this disease.

Metabolic Heterogeneity of Tumor Cells and its Impact on Colon Cancer Metastasis: Insights from Single-Cell and Bulk Transcriptome Analyses.

Background: Metabolic reprogramming plays a crucial role in the development of colorectal cancer (CRC), influencing tumor heterogeneity, the tumor microenvironment, and metastasis. While the interaction between metabolism and CRC is critical for developing personalized treatments, gaps remain in understanding how tumor cell metabolism affects prognosis. Our study introduces novel insights by integrating single-cell and bulk transcriptome analyses to explore the metabolic landscape within CRC cells and its mechanisms influencing disease progression. This approach allows us to uncover metabolic heterogeneity and identify specific metabolic genes impacting metastasis, which have not been thoroughly examined in previous studies. Methods: We sourced microarray and single-cell RNA sequencing datasets from the Gene Expression Omnibus (GEO) and bulk sequencing data for CRC from The Cancer Genome Atlas (TCGA). We employed Gene Set Variation Analysis (GSVA) to assess metabolic pathway activity, consensus clustering to identify CRC-specific transcriptome subtypes in bulkseq, and rigorous quality controls, including the exclusion of cells with high mitochondrial gene expression in scRNA seq. Advanced analyses such as AUCcell, infercnvCNV, Non-negative Matrix Factorization (NMF), and CytoTRACE were utilized to dissect the cellular landscape and evaluate pathway activities and tumor cell stemness. The hdWGCNA algorithm helped identify prognosis-related hub genes, integrating these findings using a random forest machine learning model. Results: Kaplan-Meier survival curves identified 21 significant metabolic pathways linked to prognosis, with consensus clustering defining three CRC subtypes (C3, C2, C1) based on metabolic activity, which correlated with distinct clinical outcomes. The metabolic activity of the 13 cell subpopulations, particularly the epithelial cell subpopulation with active metabolic levels, was evaluated using AUCcell in scRNA seq. To further analyze tumor cells using infercnv, NMF disaggregated these cells into 10 cellular subpopulations. Among these, the C2 subpopulation exhibited higher stemness and tended to have a poorer prognosis compared to C6 and C0. Conversely, the C8, C3, and C1 subpopulations demonstrated a higher level of the five metabolic pathways, and the C3 and C8 subpopulations tended to have a more favorable prognosis. hdWGCNA identified 20 modules, from which we selected modules primarily expressed in high metabolic tumor subgroups and highly correlated with clinical information, including blue and cyan. By applying variable downscaling of RF to a total of 50 hub genes, seven gene signatures were obtained. Furthermore, molecules that were validated to be protective in GEO were screened alongside related molecules, resulting in the identification of prognostically relevant molecules such as UQCRFS1 and GRSF1. Additionally, the expression of GRSF1 was examined in colon cancer cell lines using qPCR and phenotypically verified by in vitro experiments. Conclusion: Our findings emphasize that high activity in specific metabolic pathways, including pyruvate metabolism and the tricarboxylic acid cycle, correlates with improved colon cancer outcomes, presenting new avenues for metabolic-based therapies. The identification of hub genes like GRSF1 and UQCRFS1 and their link to favorable metabolic profiles offers novel insights into tumor neovascularization and metastasis, with significant clinical implications for targeting metabolic pathways in CRC therapy.

Risk factors that impact long-term outcomes in sigmoid colon cancer with urinary bladder involvement.

This study aimed to identify the risk factors impacting long-term outcomes in patients diagnosed with sigmoid colon cancer with urinary bladder involvement. A comprehensive analysis was conducted on a retrospective cohort of 118 patients who underwent multivisceral resection for sigmoid colon cancer with urinary bladder involvement between June 2002 and May 2017. Univariate and multivariate analyses were employed to identify risk factors associated with long-term outcomes. Among the included patients, 10 (8.5%) experienced grade III-IV complications according to Clavien-Dindo classification, with 4 (3.4%) presenting anastomotic leaks. The postoperative mortality was 0.8%. R0 resection was achieved in 108 (91.6%) patients. Adjuvant chemotherapy was administrated to only 31 patient (26.3%). Local recurrence was observed in 8 (6.8%) cases. Risk factors for local recurrence-free survival and disease-free survival were CCI>3, grade III-IV postoperative complications according to Clavien-Dindo classification, positive resection margins, stage III of the disease, additional resected organs (excluding colon and bladder) and the absence of adjuvant chemotherapy. The same risk factors, with the exception of CCI, were associated with overall survival. This study highlights that negative resection margins, a postoperative period without grade III-IV complications, and the implementation of adjuvant chemotherapy are crucial factors contributing to improve overall, disease-free and local recurrence-free survival in patients with sigmoid colon cancer with urinary bladder involvement.

ASO Author Reflections: Disparities in Colon Cancer Outcomes Exist Irrespective of Hospital Performance-System-Wide Changes Are Needed to Help Close the Gap.

ASO Author Reflections: Disparities in Colon Cancer Outcomes Exist Irrespective of Hospital Performance-System-Wide Changes Are Needed to Help Close the Gap.

Investigating the Diagnostic and Therapeutic Potential of SREBF2-Related Lipid Metabolism Genes in Colon Cancer.

Colon cancer is one of the leading causes of death worldwide, and screening of effective molecular markers for the diagnosis is prioritised for prevention and treatment. This study aimed to investigate the diagnostic and predictive potential of genes related to the lipid metabolism pathway, regulated by a protein called sterol-regulatory element-binding transcription Factor 2 (SREBF2), for colon cancer and patient outcomes. We used machine-learning algorithms to identify key genes associated with SREBF2 in colon cancer based on a public database. A nomogram was created to assess the diagnostic value of these genes and validated in the Cancer Genome Atlas. We also analysed the relationship between these genes and the immune microenvironment of colon tumours, as well as the correlation between gene expression and clinicopathological characteristics and prognosis in the China Medical University (CMU) clinical cohort. Three genes, 7-dehydrocholesterol reductase (DHCR7), hydroxysteroid 11-beta dehydrogenase 2 (HSD11B2), and Ral guanine nucleotide dissociation stimulator-like 1 (RGL1), were identified as hub genes related to SREBF2 and colon cancer. Using the TCGA dataset, receiver operating characteristic curve analysis showed the area under the curve values of 0.943, 0.976, and 0.868 for DHCR7, HSD11B2, and RGL1, respectively. In the CMU cohort, SREBF2 and DHCR7 expression levels were correlated with TNM stage and tumour invasion depth (P < 0.05), and high DHCR7 expression was related to poor prognosis of colon cancer (P < 0.05). Furthermore, DHCR7 gene expression was positively correlated with the abundance of M0 and M1 macrophages and inversely correlated with the abundance of M2 macrophages, suggesting that the immune microenvironment may play a role in colon cancer surveillance. There was a correlation between SREBF2 and DHCR7 expression across cancers in the TCGA database. This study highlights the potential of DHCR7 as a diagnostic marker and therapeutic target for colon cancer.

Integrative analysis of co-expression pattern of solute carrier transporters reveals molecular subtypes associated with tumor microenvironment hallmarks and clinical outcomes in colon cancer

Recent findings have suggested that solute carrier (SLC) transporters play an important role in tumor development and progression, and alterations in the expression of individual SLC genes are critical for fulfilling the heightened metabolic requirements of cancerous cells. However, the global influence of the co-expression pattern of SLC transporters on the clinical stratification and characteristics of the tumor microenvironment (TME) remains unexplored. In this study, we identified five SLC gene subtypes based on transcriptome co-expression patterns of 187 SLC transporters by consensus clustering analysis. These subtypes, which were characterized by distinct TME and biological characteristics, were successfully employed for prognostic and chemotherapy response prediction in colon cancer patients, as well as demonstrated associations with immunotherapy benefits. Then, we generated an SLC score model comprising 113 genes to quantify SLC gene co-expression patterns and validated it as an independent prognostic factor and drug response predictor in several independent colon cancer cohorts. Patients with a high SLC score possessed distinct characteristics of copy number variation, genomic mutations, DNA methylation, and indicated an SLC-S2 subtype, which was characterized by strong stromal cell infiltration, stromal pathway activation, poor prognosis, and low predicted fluorouracil and immunotherapeutic responses. Furthermore, the analysis of the Cancer Therapeutics Response Portal database revealed that inhibitors targeting PI3K catalytic subunits could serve as promising chemosensitizing agents for individuals exhibiting high SLC scores. In conclusion, the co-expression patterns of SLC transporters aided the disease classification, and the SLC score proved to be a reliable tool for distinguishing SLC gene subtypes and guiding precise treatment in patients with colon cancer.

YTE-17 inhibits colonic carcinogenesis by resetting antitumor immune response via Wnt5a/JNK mediated metabolic signaling

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer. Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis (YTE-17), attributing these effects to the regulation of multiple signaling pathways. However, knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited. In this study, we conducted isobaric tags for relative and absolute quantification (iTRAQ) analysis on intestinal epithelial cells (IECs) exposed YTE-17, both in vitro and invivo, revealing a significant inhibition of the Wnt family member 5a (Wnt5a)/c-Jun N-terminal kinase (JNK) signaling pathway. Subsequently, we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment (TME), specifically focusing on macrophage-mediated T helper 17 (Th17) cell induction in a colitis-associated cancer (CAC) model with Wnt5a deletion. Additionally, we performed the single-cell RNA sequencing (scRNA-seq) on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition, lineage, and functional status of immune mesenchymal cells during different stages of colorectal cancer (CRC) progression. Remarkably, our findings demonstrate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17, leading to the restoration of regulatory T (Treg)/Th17 cell balance in azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Furthermore, we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages. Notably, our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo. Specifically, we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME, involving macrophages and T cells. In summary, our study undergoes the potential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment, thereby mitigating the risk of malignancies.

KRAS mutations and their associations with clinicopathological features and survival in Vietnamese non‑polyp colon cancer patients.

The aim of the present study was to determine Kirsten Ras sarcoma virus (KRAS) mutations and the associations of KRAS mutations with clinicopathological features and treatment outcomes in Vietnamese non-polyp colon cancer (NPCC) patients. The data in the present study covered 194 patients with non-polyp colon cancers at stages II or III, according to the 8th edition of the American Joint Committee on Cancer staging system, in northern Vietnam from January 2016 to August 2020. All patients underwent radical surgery and adjuvant therapy with FOLFOX4 or XELOX. Subsequently, the recruited patients were followed-up with scheduled hospital exams for diagnosing recurrence. Genomic DNA samples were prepared from dissected tumors and specific sequences of the KRAS gene were amplified by polymerase chain reactions (PCR). The mutations at codons 12, 13, 59, 60, 61, 117 and 146 of the gene were determined. Possible associations of the KRAS mutations with clinicopathological properties and the survival of patients were analysed. The KRAS mutation rate was 47.9% in Vietnamese patients with NPCC, of those, mutations in exon 2 accounted for 91.4% of all detected mutations. The mutated-KRAS patients exhibited a significantly higher rate of anemia. Moreover, the KRAS mutation rate was higher in females (57.1%) than in males (39.8%). The KRAS mutation rate was also higher in patients with right colon cancers. Furthermore, KRAS mutations were an independent prognosis for poor disease-free survival (DFS) and overall survival (OS) in stage II patients. Among left-sided colon patients, mutated KRAS was a significant predictive factor for poor DFS but not for OS. The present study revealed a very high mutation rate of KRAS in Vietnamese patients with NPCC. The data of the present study indicated that the mutation status was associated with female patients and right-sided tumors. The KRAS mutations were a negative factor for the survival of patients with stage II NPCC and patients with left-sided colon cancer.

The impact of laparoscopic, open, extended right, and left colectomy on clinical outcomes of splenic flexure colon cancer: A meta-analysis.

Surgical intervention is the recommended line for the management of colon cancer. The aim of this study was to evaluate the impact of different surgical techniques (laparoscopic, open, extended right, and left colectomy) on clinical outcomes such as mortality, postoperative complications, operation and hospitalization time, and oncological factors. A total of 15 studies have been included in the current study. The outcomes of these studies were analyzed using a random-effect model and it was used to calculate the mean difference with 95% confidence intervals to quantify the impact of open, laparoscopic, extended right, and left colectomy. Inclusion criteria included studies in which subjects undergo splenic flexure colon cancer surgery with 2 comparable different surgical techniques. Laparoscopic splenic flexure colon cancer surgery showed a significant beneficial impact on the length of hospital stay (P < .001), the volume of blood loss during surgery (P < .001), postoperative complications (P < .001), and time to an oral diet (P < .001). On the other hand, there was no significance regarding anastomotic leakage, infection of the surgical site, and operation time. Regarding the comparison between extended right colectomy (ERC) and lift colectomy (LC), analysis findings showed a significant (P = .001) higher efficacy of ERC in harvested number of lymph nodes compared with LC. On the other hand, there was no significant difference for the rest of the parameters. The neoadjuvant therapy as an influencing factor on postoperative outcome showed a beneficial impact regarding the overall survival rate. Laparoscopic splenic flexure colon cancer surgery showed a significant beneficial impact compared with open surgery as proved by clinical outcomes. On the other hand, ERC and LC resulted in similar findings except for harvested lymph nodes, results were in favor of ERC.

Chemotherapy Treatment Costs and Clinical Outcomes of Colon Cancer in the U.S. Military Health System's Direct and Private Sector Care Settings.

Identifying low-value cancer care may be an important step in containing costs associated with treatment. Low-value care occurs when the medical services, tests, or treatments rendered do not result in clinical benefit. These may be impacted by care setting and patients' access to care and health insurance. We aimed to study chemotherapy treatment and the cost paid by the Department of Defense (DoD) for treatment in relation to clinical outcomes among patients with colon cancer treated within the U.S. Military Health System's direct and private sector care settings to better understand the value of cancer care. A cohort of patients aged 18 to 64 years with primary colon cancer diagnosed between January 1, 1999, and December 31, 2014, were identified in the Military Cancer Epidemiology database. Multivariable time-dependent Cox proportional hazards regression models were used to assess the relationship between chemotherapy treatment and the cost paid by the DoD (in quartiles, Q) and the outcomes of cancer progression, cancer recurrence, and all-cause death modeled as adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). The Military Cancer Epidemiology data were approved for research by the Uniformed Services University of the Health Sciences' Institutional Review Board. The study included 673 patients using direct care and 431 patients using private sector care. The median per patient chemotherapy costs in direct care ($111,202) were lower than in private sector care ($350,283). In direct care, higher chemotherapy costs were associated with an increased risk of any outcome but not with all-cause death. In private sector care, higher chemotherapy costs were associated with a higher risk of any outcome and with all-cause death (aHR, 2.67; 95% CI, 1.20-5.92 for Q4 vs. Q1). The findings in the private sector may indicate low-value care in terms of the cost paid by the DoD for chemotherapy treatment and achieving desirable survival outcomes for patients with colon cancer in civilian health care. Comprehensive evaluations of value-based care among patients treated for other tumor types may be warranted.

Association between Ki67 expression and therapeutic outcome in colon cancer.

Ki67 is a commonly used proliferation marker in pathological diagnosis of tumors; however, its prognostic value in colon cancer is controversial. A total of 312 consecutive patients with stage I-III colon cancer who underwent radical surgery with or without adjuvant chemotherapy were included in the present study. Ki67 expression was assessed using immunohistochemistry and was classified according to 25% intervals. The association between Ki67 expression and clinicopathological features was analyzed. Long-term postoperative survival, including disease-free survival (DFS) and overall survival, was calculated, and its association with Ki67 was analyzed. High Ki67 expression (>50%) was associated with improved DFS in patients treated with adjuvant chemotherapy postoperatively, but not in patients who received surgery alone (P=0.138). Ki67 expression was significantly associated with histological differentiation of the tumor (P=0.01), while it was not associated with other clinicopathological factors. Multivariate analysis demonstrated that pathological T and N stage were independent prognostic factors. In conclusion, high Ki67 expression was associated with a good therapeutic outcome in patients receiving adjuvant chemotherapy in colon cancer.

Exploring the complexity and spectrum of racial/ethnic disparities in colon cancer management

BackgroundColorectal cancer is a leading cause of morbidity and mortality across U.S. racial/ethnic groups. Existing studies often focus on a particular race/ethnicity or single domain within the care continuum. Granular exploration of disparities among different racial/ethnic groups across the entire colon cancer care continuum is needed. We aimed to characterize differences in colon cancer outcomes by race/ethnicity across each stage of the care continuum.MethodsWe used the 2010–2017 National Cancer Database to examine differences in outcomes by race/ethnicity across six domains: clinical stage at presentation; timing of surgery; access to minimally invasive surgery; post-operative outcomes; utilization of chemotherapy; and cumulative incidence of death. Analysis was via multivariable logistic or median regression, with select demographics, hospital factors, and treatment details as covariates.Results326,003 patients (49.6% female, 24.0% non-White, including 12.7% Black, 6.1% Hispanic/Spanish, 1.3% East Asian, 0.9% Southeast Asian, 0.4% South Asian, 0.3% AIAE, and 0.2% NHOPI) met inclusion criteria. Relative to non-Hispanic White patients: Southeast Asian (OR 1.39, p < 0.01), Hispanic/Spanish (OR 1.11 p < 0.01), and Black (OR 1.09, p < 0.01) patients had increased odds of presenting with advanced clinical stage. Southeast Asian (OR 1.37, p < 0.01), East Asian (OR 1.27, p = 0.05), Hispanic/Spanish (OR 1.05 p = 0.02), and Black (OR 1.05, p < 0.01) patients had increased odds of advanced pathologic stage. Black patients had increased odds of experiencing a surgical delay (OR 1.33, p < 0.01); receiving non-robotic surgery (OR 1.12, p < 0.01); having post-surgical complications (OR 1.29, p < 0.01); initiating chemotherapy more than 90 days post-surgery (OR 1.24, p < 0.01); and omitting chemotherapy altogether (OR 1.12, p = 0.05). Black patients had significantly higher cumulative incidence of death at every pathologic stage relative to non-Hispanic White patients when adjusting for non-modifiable patient factors (p < 0.05, all stages), but these differences were no longer statistically significant when also adjusting for modifiable factors such as insurance status and income.ConclusionsNon-White patients disproportionately experience advanced stage at presentation. Disparities for Black patients are seen across the entire colon cancer care continuum. Targeted interventions may be appropriate for some groups; however, major system-level transformation is needed to address disparities experienced by Black patients.

Ten-Year Recurrence Outcomes in Early Stage and Early Onset Colon Cancer and the Expression Profiles of MicroRNAs and Cancer Stem Cell Markers in These Tumors

Objective: We hypothesized that microRNAs (miRNAs) might be involved in tumor development by critically regulating cancer stem cell (CSC) markers in the early stages of colon cancer (eCC). This study aimed to determine the expression profiles of miRNAs in CSC-positive eCC patients and examine their associations with recurrence. Materials and Methods: We analyzed CD133, LGR5 and SOX2 expression profiles to determine CSC status in 30 eCC specimens. Then, using the results of RT2 miRNA PCR custom arrays, we evaluated the expression profiles of 38 miRNAs in CSC-positive eCC patients. Results: Recurrence occurred in 5 patients within ten years after surgery. We determined down-regulation of miR-125b and up-regulation of miR-135b were significant in CSC-positive eCC patients (p=0.021, p=0.001, respectively). We found that low expression of miR-125b was associated with recurrence in eCC (p=0.0022). Conclusions: We suggest that recurrence might be prevented by increasing the expression of miR-125b in eCC.

Artificial intelligence to investigate predictors and prognostic impact of time to surgery in colon cancer.

The role of time to surgery (TTS) for long-term outcomes in colon cancer (CC) remains ill-defined. We sought to utilize artificial intelligence (AI) to characterize the drivers of TTS and its prognostic impact. The National Cancer Database was utilized to identify patients diagnosed with non-metastatic CC between 2004 and 2018. AImodels were employed to rank the importance of several sociodemographic, facility, and tumor characteristics in determining TTS, and postoperative survival. Among 518 983 patients, 137 902 (26.6%) received intraoperative diagnosis of CC (TTS = 0), while 381 081 (74.4%) underwent elective surgery (TTS > 0) with median TTS of 19.0 days (interquartile range[IQR]: 7.0-33.0). An AI model, identified tumor stage, receipt of adequate lymphadenectomy, histologic grade, lymphovascular invasion, and insurance status as the most important variables associated with TTS = 0. Conversely, the type and location of treating facility and receipt of adjuvant therapy were among the most important variables for TTS > 0. Notably, TTS was among the most important variables associated with survival, and TTS > 3 weeks was associated with anincremental increase in mortality risk. The identification of factors associated with TTS can help stratify patients most likely to suffer poor outcomes due to prolonged TTS, aswellas guide quality improvement initiatives relatedto timely surgical care.

Clinical outcomes and healthcare utilization among young adults with colon cancer on Medicaid vs private insurance.

22 Background: The incidence of colon cancer in young adults has been increasing. The role of insurance on the outcomes of young adults diagnosed with colon cancer is unclear. In this study we sought to study the impact of Private insurance vs Medicaid on the outcomes of colon cancer in young adults (&lt;50 years). Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) 2016-2019 was queried to identify young adult patients (Age &lt;50 years) admitted for colon cancer using the ICD-10 (International Classification of Diseases) codes. Study population was stratified based on the insurance (private vs Medicaid). Primary outcomes included mortality, length of stay (LOS), and total hospitalization charges (THC). Secondary outcomes included prevalence of pulmonary embolism (PE), ICU admission, acute kidney injury (AKI), acute respiratory failure (ARF), blood transfusion, and sepsis. Statistics were performed using multivariate linear and logistic regression using STATA v17. Results: 59,065 young adult admissions were identified with a principal diagnosis of colon cancer between 2016-2019. Among them 36,765 (62.2%) were on private insurance while 13,480 (22.8%) were on Medicaid. Medicaid patients were significantly younger, female, Black and Hispanic with a higher Charlson comorbidity index (p&lt;0.05). Of the 870 (1.5%) patients that died during the admission, 46.5% (N= 405) had private insurance whereas 26.4% (N= 230) had Medicaid. There was no significant difference in the odds of mortality between private insurance and Medicaid (adjusted OR 1.07, 95% CI 0.69-1.67; p=0.77). The LOS was increased by 1.5 days for Medicaid patients compared to private insurance (95% CI 1.15-1.90; p&lt;0.001). There was no significant difference in total hospitalization charges among both groups. Medicaid patients had higher odds of sepsis (OR 1.5, 95% CI 1.09-1.94; p=0.012), requiring blood transfusion (OR 1.6, 95% CI 1.32-1.83; p&lt;0.000) and less likely to undergo colectomy (OR 0.61, 95% CI 0.55-0.67; p&lt;0.000). There were no significant differences in ICU admission, AKI and ARF. Conclusions: Compared to private insurance, Medicaid patients had similar healthcare outcomes and hospital charges despite a longer LOS. In an era where the country explores options for healthcare reform including single payor system, our study provides insight into similar effectiveness of Medicaid in caring for young colon cancer patients compared to Private Insurance despite higher comorbidities in Medicaid patients.

A Novel Prognostic Index for Metastatic Colon Cancer: The Prognostic Immune Nutritional Index.

Objective Systemic inflammation and nutrition are associated with survival outcomes in metastatic colon cancer (mCC) patients. A new and strong prognostic marker named the Prognostic Immune Nutritional Index (PINI) was proposed as the best marker for outcomes in metastatic colon cancer patients. This study aimed to evaluate the prognostic significance of PINI in mCC patients. Methods The data of 190 patients who were admitted to our center and diagnosed with mCC between 2010 and 2020 abiding by our inclusion criteria were reviewed retrospectively. Receiver operating characteristic (ROC) analysis was used to identify the optimum cutoff value of PINI for overall survival (OS). Results The mean age of the participants was 62.64±11.99 years. The median follow-up time was 25.81 months. According to PINI, the median OS in patients who had PINI<3 was 22.70 months (95% confidence interval (CI): 16.05-29.35), and the median OS in patients who had PINI≥3 was 38.83 months (95% CI: 26.98-37.01) (p<0.001). PINI score lower than 3 was an independent prognostic indicator in multivariate analysis. Conclusions PINI was discovered to be an independent prognostic factor in metastatic colorectal cancer. We believe that PINI, which can be calculated using a simple formula, will provide clinicians with important clues when deciding on individual treatment.

Comparing the techniques and outcomes of laparoscopic transverse colectomy to laparoscopic hemicolectomy in mid-transverse colon cancer resection.

The mid-transverse colon cancer is relatively uncommon in all colon cancers and the optimal surgical approach of mid-transverse colon cancer remains debatable. Our study aimed to depict the techniques and outcomes of laparoscopic transverse colectomy in one single clinical center and compare this surgical approach to traditional laparoscopic right hemicolectomy and laparoscopic left hemicolectomy. This was a retrospective cohort study of patients with mid-transverse colon cancer in one single clinical center from February 2012 to October 2020. The enrolled patients were divided into two groups undergoing laparoscopic transverse colectomy and laparoscopic right/left hemicolectomy, respectively. The intraoperative, postoperative complications, oncological outcomes and functional outcomes were compared between the two groups. The primary endpoint was disease free survival (DFS). The study enrolled 70 patients with 40 patients undergoing laparoscopic transverse colectomy and 30 patients undergoing laparoscopic hemicolectomy. The intraoperative accidental hemorrhage and multiple organ resection occurred similarly in the two groups. In transverse colectomy, caudal-to-cephalic approach was likely to harvest more lymph nodes although require more operation time than cephalic-to-caudal approach (23.1 ± 14.3 vs. 13.4 ± 5.4 lymph nodes, P = 0.004; 184.3 ± 37.1 min vs. 146.3 ± 44.4 min, P = 0.012). The laparoscopic transverse colectomy was marginally associated with lower incidence of overall postoperative complications and shorter postoperative hospital stay although without statistical significance (8(20.0%) vs. 12(40.0%), P = 0.067; 7(5-12) vs. 7(5-18), P = 0.060). The 3-year DFS showed no significant difference (3-year DFS 89.7% in transverse colectomy vs. 89.9% in hemicolectomy, P = 0.688) between the two groups. The alternating consistency of defecation occurred significantly less after laparoscopic transverse colectomy than laparoscopic hemicolectomy (15(51.7%) vs. 20(80.0%), P = 0.030). The laparoscopic transverse colectomy is technically feasible with satisfactory oncological and functional outcomes for mid-transverse colon cancer. Performing the caudal-to-cephalic approach might be more advantageous in lymphadenectomy.

Computed Tomography-based Radiomics Nomogram for the Preoperative Prediction of Tumor Deposits and Clinical Outcomes in Colon Cancer: a Multicenter Study

To develop and validate a computed tomography (CT)-based radiomics nomogram for the preoperative prediction of tumor deposits (TDs) and clinical outcomes in patients with colon cancer. This retrospective study included 383 consecutive patients with colon cancer from two centers. Radiomics features were extracted from portal venous phase CT images. Least absolute shrinkage and selection operator regression was applied for feature selection and radiomics signature construction. The multivariate logistic regression model was used to establish a radiomics nomogram. The performance of the nomogram was assessed by using receiver operating characteristic curves, calibration curves and decision curve analysis. Kaplan‒Meier survival analysis was used to assess the difference of the overall survival (OS) in the TDs-positive and TDs-negative groups. The radiomics signature was composed of 11 TDs status related features. The AUCs of the radiomics model in the training cohort, internal validation and external validation cohorts were 0.82, 0.78 and 0.78, respectively. The radiomics nomogram that incorporated the radiomics signature and clinical independent predictors (CT-N, CEA and CA199) showed good calibration and discrimination with AUCs of 0.88, 0.80 and 0.81 in the training cohort, internal validation and external validation cohorts, respectively. The radiomics nomogram-predicted high-risk groups had a worse OS than the low-risk groups (p < 0.001). The radiomics nomogram-predicted TDs was an independent preoperative predictor of OS. The radiomics nomogram based on CT radiomics features and clinical independent predictors could effectively predict the preoperative TDs status and OS of colon cancer. CT-based radiomics nomogram may be applied in the individual preoperative prediction of TDs status in colon cancer. Additionally, there was a significant difference in OS between the high-risk and low-risk groups defined by the radiomics nomogram, in which patients with high-risk TDs had a significantly worse OS, compared with those with low-risk TDs.

Mutant RIG-I enhances cancer-related inflammation through activation of circRIG-I signaling

RIG-I/DDX58 plays a key role in host innate immunity. However, its therapeutic potential for inflammation-related cancers remains to be explored. Here we identify frameshift germline mutations of RIG-I occurring in patients with colon cancer. Accordingly, Rig-ifs/fs mice bearing a frameshift mutant Rig-i exhibit increased susceptibility to colitis-related colon cancer as well as enhanced inflammatory response to chemical, virus or bacteria. In addition to interruption of Rig-i mRNA translation, the Rig-i mutation changes the secondary structure of Rig-i pre-mRNA and impairs its association with DHX9, consequently inducing a circular RNA generation from Rig-i transcript, thereby, designated as circRIG-I. CircRIG-I is frequently upregulated in colon cancers and its upregulation predicts poor outcome of colon cancer. Mechanistically, circRIG-I interacts with DDX3X, which in turn stimulates MAVS/TRAF5/TBK1 signaling cascade, eventually activating IRF3-mediated type I IFN transcription and aggravating inflammatory damage. Reciprocally, all-trans retinoic acid acts as a DHX9 agonist, ameliorates immunopathology through suppression of circRIG-I biogenesis. Collectively, our results provide insight into mutant RIG-I action and propose a potential strategy for the treatment of colon cancer.

64P Clinical profile and treatment outcome of patients with non-metastatic colon cancer: A single institutional study from India

Colo rectal cancer is the third most common cancer in the world. Clinical data on localized colon cancer and treatment outcome is scarce in the literature. This is a real-world study of the clinical profile and treatment patterns and outcomes of patients with nonmetastatic colon cancer from India. Here we report our experience in this patient population.