Outcome In Colon Cancer Patients Research Articles

Development and validation of a prognostic model for colon cancer based on mitotic gene signatures and immune microenvironment analysis

BackgroundMitotic processes play a pivotal role in tumor progression and immune responses. However, the correlation between mitosis-related genes, clinical outcomes, and the tumor microenvironment (TME) in colon cancer remains unclear. This study aims to develop a prognostic and therapeutic significance model for colon cancer based on mitosis-related genes.MethodsRNA expression profiles and clinical data of 453 colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA). Mitosis-related genes were selected from the MsigDb database. The gene model was constructed using differential analysis, univariate and multivariate Cox regression, and Lasso regression analyses. The predictive model was validated using data from the GSE17536, GSE17537, and GSE39582 datasets. Predictive accuracy was evaluated via Receiver Operating Characteristic (ROC) curves, while nomograms were developed by integrating clinical and pathological features. Gene set enrichment analysis explored biological processes and pathways linked to the model. TME was assessed using ESTIMATE, and the proportion and function of immune cells were analyzed through CIBERSORT. Drug sensitivity analysis was conducted using the CTRP database.ResultsA predictive model based on 17 mitosis-related genes (KIFC1, CCNF, EME1, CDC25C, ORC1, CCNJL, ANKRD53, MEIS2, FZD3, TPD52L1, MAPK3, CDKN2A, EDN3, NPM2, PSRC1, INHBA, BIRC5) was created. The model exhibited robust predictive performance across both training and validation cohorts. Nomograms for predicting 3-, 5-, and 7-year survival rates in colon cancer (COAD) patients were generated. The model's correlation with immune cell infiltration and function was highlighted.ConclusionThe mitosis-related gene model serves as a valuable indicator for predicting survival outcomes in colon cancer patients.

The impact of facility type on surgical outcomes in colon cancer patients: analysis of the national cancer database.

The type of facility wherepatients with colon cancer are treated may play a significant role in their outcomes. We aimed to investigate the influence of facility types included in the National Cancer Database (NCDB) on surgical outcomes of colon cancer. Retrospective cohort analysis of all patients with stage I-III colon cancer included in the NCDB database between 2010 and 2019 was performed. Patients were grouped based on facility type: Academic/Research Programs (ARP), Community Cancer Programs (CCP), Comprehensive Community Cancer Programs (CCCP), and Integrated Network Cancer Programs (INCP). Studyoutcomes included overall survival, 30- and 90-day mortality, 30-day readmission and conversion to open surgery. 125,935 patients were included with a median age of 68.7years (50.5% females). Most tumors were in the right colon (50.6%). Patient were distributed among facility types as ARP (n = 34,321, 27%), CCP (n = 12,692, 10%), CCCP (n = 54,356, 43%), and INCP (n = 24,566, 19%). In terms of surgical approach, laparoscopy was more commonly used in ARP (46%) (p < 0.001). Laparotomy was more common in CCP (58.7%) (p < 0.001), and conversely, CCP had the least amount of robotic surgery (3.9%) (p < 0.001). Median overall survival was highest in ARP (129months, 95% CI 127.4-134.1) and lowest in CCP (103.7months, 95% CI 100.1-106.7) (p < 0.001). Conversion rates were comparable between ARP (12%), CCCP (12%) and INCP (11.8%) but were higher in CCP (15.5%) (p < 0.001). 30-day readmission rates and 30-day mortality rates were significantly lower in ARP compared to other facility types (p < 0.001). Our findings display differences in surgical outcomes of colon cancer patients among facility types. The findings suggest better outcomes in terms of operative access and survival at ARP as compared to other facilities. These findings underscore the importance of understanding facility-specific factors that may influence patient outcomes and can guide resource allocation and targeted interventions for improving colon cancer care.

Primary Tumor Sidedness Associated with Clinical Characteristics and Postoperative Outcomes in Colon Cancer Patients: A Propensity Score Matching Analysis.

Background: Recent investigations have suggested that-sidedness is associated with the prognosis of colon cancer patients. However, the role of sidedness in surgical outcome is unclear. In this study, we tried to demonstrate the real role of sidedness in postoperative results for colon cancer patients receiving surgical intervention. Methods: This is a propensity score matching study using the database of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) from 2009 to 2013. Sidedness groups including right-sided and left-sided colon cancer were created according to the associated diagnosis and procedure codes. Postoperative 30-day mortality, morbidity, overall complications, and total length of hospital stay were analyzed after performing propensity score matching. Results: Out of a total of 24,436 colon cancer patients who received associated operations, 15,945 patients had right-sided cancer and 8941 patients had left-sided cancer. Right-sided colon cancer patients were accompanied by more preoperative comorbidities including old age, female sex, hypertension, dyspnea, anemia, hypoalbuminemia, and a high American Society of Anesthesiologists grade (SMD > 0.1). Postoperative mortality, morbidities including re-intubation, bleeding, urinary tract infection and deep vein thrombosis, postoperative overall complications, and total length of hospital stay were significantly associated with right-sided cancer (p < 0.05). After 1:1 propensity score matching, postoperative mortality was not significantly different between right-sided cancer (2.3%) and left-sided cancer (2.4%) patients. The patients with left-sided colon cancer had significantly more postoperative morbidities, more overall complications, and longer total length of hospital stay. Conclusions: Poor clinical characteristics and postoperative outcomes were noted in right-sided cancer patients. After propensity score matching, left-sided cancer patients had worse postoperative outcomes than those with right-sided cancer.

Inactivation of pentraxin 3 suppresses M2-like macrophage activity and immunosuppression in colon cancer

BackgroundThe tumor microenvironment is characterized by inflammation-like and immunosuppression situations. Although cancer-associated fibroblasts (CAFs) are among the major stromal cell types in various solid cancers, including colon cancer, the interactions between CAFs and immune cells remains largely uncharacterized. Pentraxin 3 (PTX3) is responsive to proinflammatory cytokines and modulates immunity and tissue remodeling, but its involvement in tumor progression appears to be context-dependent and is unclear.MethodsOpen-access databases were utilized to examine the association of PTX3 expression and the fibroblast signature in colon cancer. Loss-of-function assays, including studies in tamoxifen-induced Ptx3 knockout mice and treatment with an anti-PTX3 neutralizing antibody (WHC-001), were conducted to assess the involvement of PTX3 in colon cancer progression as well as its immunosuppressive effect. Finally, bioinformatic analyses and in vitro assays were performed to reveal the downstream effectors and decipher the involvement of the CREB1/CEBPB axis in response to PTX3 and PTX3-induced promotion of M2 macrophage polarization.ResultsClinically, higher PTX3 expression was positively correlated with fibroblasts and inflammatory response signatures and associated with a poor survival outcome in colon cancer patients. Blockade of PTX3 significantly reduced stromal cell-mediated tumor development. The decrease of the M2 macrophage population and an increase of the cytotoxic CD8+ T-cell population were observed following PTX3 inactivation in allografted colon tumors. We further revealed that activation of cyclic AMP-responsive element-binding protein 1 (CREB1) mediated the PTX3-induced promotion of M2 macrophage polarization.ConclusionsPTX3 contributes to stromal cell-mediated protumor immunity by increasing M2-like macrophage polarization, and inhibition of PTX3 with WHC-001 is a potential therapeutic strategy for colon cancer.

Effects of First Wave of COVID-19 on Colon Cancer Multi-disciplinary Team Performance: A Two-Year Analysis.

We investigated the effects of COVID-19-related delay on two-year outcomes of colon cancer treatment during the first wave of the pandemic. Ninety-two patients were referred for bowel cancer at our National Health Service (NHS) trust between March and July 2020, and 41 patients were treated for colon cancer and followed up (a two-year) through a multidisciplinary team (MDT). Treatment delays and overall survival (OS) were also assessed. Treatment delays were observed in 48% of patients. The average delay was 31 days beyond the 62-day mark (P0.001). Logistic and binary logistic regression models showed that a comorbid diagnosis of respiratory disease had a significant effect on delays in management and two-year outcomes (P=0.04), but without the likelihood of upstaging or a poorer outcome (P=0.942). The overall survival rate was 81.5%. Eight percent of bowel cancer surgeries could have been avoided if endoscopic visualization and biopsy were available, and 8% more surgeries could have been performed laparoscopically without fear of surrounding aerosols. The findings showed that oncologic care provided minimal disruption to trust during the COVID-19 pandemic owing to a quick association between the NHS site and a green non-NHS site, resulting in acceptable two-year outcomes for colon cancer patients.

Abstract C172: PTX3 blockade restores anti-tumor immunity through suppressing M2-like macrophages phenotypes in colon cancer

Abstract The tumor microenvironment is a chronic inflammatory condition which is composed of various types of stromal cells, immune cells, and cytokines. Cancer-associated fibroblasts and M2-like macrophages are involved in enhancing malignancy of colon cancer progression, such as tumor growth and immunosuppression. Identifying the cross-talk mechanisms among cancer cells, cancer-associated fibroblasts, and M2-like macrophages is important for development of cancer therapy. Pentraxin 3 (PTX3) is a secretory factor that is rapidly responsive to exposure of proinflammatory cytokines. The function of PTX3 is known to regulate innate immunity and tissue remodeling. However, its role in tumor progression appears to be context-dependent and unclear. In this study, we found that PTX3 is silenced in colon cancer cells due to epigenetic regulation but is primarily expressed by fibroblasts in colon tumors. Clinically, higher PTX3 expression is positively correlated with fibroblast and inflammatory response signatures and associated with a poor survival outcome in colon cancer patients. Our results showed that PTX3 had no effect on cellular proliferation of fibroblasts or cancer cells in vitro, but blockade of PTX3 by specific monoclonal antibody significantly reduced stroma cell-mediated tumor growth in vivo. In addition, blockade of PTX3 reduced MC38 tumor growth in immunocompetent mice but had no effect in immunodeficient mice, suggesting the role of PTX3 in regulating tumor-immunity. Indeed, inhibition of PTX3 resulted in reduced numbers of M2-like macrophages and increased numbers of cytotoxic CD8 T cells in MC38 tumors. The expressions of cytotoxic markers in T cells were suppressed under exposure to conditioned media from PTX3-stimulated macrophages in vitro. We further revealed that PTX3 stimulated macrophage polarization toward an M2-like phenotype through activation of CREB/CEBPB axis. These findings suggest that PTX3 is involved in stroma cell-mediated protumoral immunity and targeting PTX3 by monoclonal antibody can be a potential therapeutic strategy in colon cancer treatment. Citation Format: Feng-Wei Chen. PTX3 blockade restores anti-tumor immunity through suppressing M2-like macrophages phenotypes in colon cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C172.

An Activated Dendritic-Cell-Related Gene Signature Indicative of Disease Prognosis and Chemotherapy and Immunotherapy Response in Colon Cancer Patients

Accumulating evidence has underscored the prognostic value of tumor-infiltrating immune cells in the tumor microenvironment of colon cancer (CC). In this retrospective study, based on publicly available transcriptome profiles and clinical data from the Gene Expression Omnibus and The Cancer Genome Atlas databases, we derived and verified an activated dendritic cell (aDC)-related gene signature (aDCRS) for predicting the survival outcomes and chemotherapy and immunotherapy response of CC patients. We quantified the infiltration abundance of 22 immune cell subtypes via the “CIBERSORT” R script. Univariate Cox proportional hazards (PHs) regression was used to identify aDC as the most robust protective cell type for CC prognosis. After selecting differentially expressed genes (DEGs) significantly correlated with aDC infiltration, we performed univariate Cox-PH regression, LASSO regression, and stepwise multivariate Cox-PH regression successively to screen out prognosis-related genes from selected DEGs for constructing the aDCRS. Receiver operating characteristic (ROC) curves and Kaplan–Meier (KM) analysis were employed to assess the discriminatory ability and risk-stratification capacity. The “oncoPredict” package, Cancer Treatment Response gene signature DataBase, and Tumor Immune Dysfunction and Exclusion algorithm were utilized to estimate the practicability of the aDCRS in predicting response to chemotherapy and immune checkpoint blockade. Gene set enrichment analysis and single-cell RNA sequencing analysis were also implemented. Furthermore, an aDCRS-based nomogram was constructed and validated via ROC curves, calibration plots and decision curve analysis. In conclusion, aDCRS and an aDCRS-based nomogram will facilitate precise prognosis prediction and individualized therapeutic interventions, thus improving the survival outcomes of CC patients in the future.

A novel investigation into an E2F transcription factor-related prognostic model with seven signatures for colon cancer patients.

The pathogenesis of colon cancer, a common gastrointestinal tumour, involves complicated factors, especially a series of cell cycle-related genes. E2F transcription factors during the cell cycle play an essential role in the occurrence of colon cancer. It is meaningful to establish an efficient prognostic model of colon cancer targeting cellular E2F-associated genes. This has not been reported previously. The authors first aimed to explore the links of E2F genes with the clinical outcomes of colon cancer patients by integrating data from the TCGA-COAD (n=521), GSE17536 (n=177) and GSE39582 (n=585) cohorts. The Cox regression and Lasso modelling approach to identify a novel colon cancer prognostic model involving several hub genes (CDKN2A, GSPT1, PNN, POLD3, PPP1R8, PTTG1 and RFC1) were utilised. Moreover, an E2F-related nomogram that efficiently predicted the survival rates of colon cancer patients was created. Additionally, the authors first identified two E2F tumour clusters, which showed distinct prognostic features. Interestingly, the potential links of E2F-based classification and 'protein secretion' issues of multiorgans and tumour infiltration of 'T-cell regulatory (Tregs)' and 'CD56dim natural killer cell' were detected. The authors' findings are of potential clinical significance for the prognosis assessment and mechanistic exploration of colon cancer.

Prognostic modelling of colorectal cancer based on oxidative stress-related genes.

Colon cancer is one of the most prevalent cancers of the digestive tract. There is mounting evidence that genes associated with oxidative stress might affect the tumour immune microenvironment during tumour growth, maintenance, and treatment response. However, how oxidative stress-related genes affect prognostic importance, tumour microenvironment features, and treatment outcomes in colon cancer patients has not been fully elucidated. The Cancer Genome Atlas (TCGA) dataset was used to construct a signature model and nomogram using step and Cox regression approaches to investigate how gene expression affected immunological responses to colon cancer, including the degree of immune infiltration, MSI, and drug sensitivity. The nomogram and the signature model had strong prognostic potential for colon cancer, with gene expression highly correlated with multiple immune cells. The first signature model and nomogram including oxidative stress-related genes were constructed for use in clinical decision-making. In addition, SRD5A1, GSR, TXN, TRAF2 and TRAP1 were identified as potential biomarkers for colon cancer diagnosis and indicators for immunotherapy.

New scoring system combining computed tomography body composition analysis and inflammatory-nutritional indicators to predict postoperative complications in stage II-III colon cancer.

Postoperative complications are important clinical outcomes for colon cancer patients. This study aimed to investigate the predictive value of inflammatory-nutritional indicators combined with computed tomography body composition on postoperative complications in patients with stage II-III colon cancer. We retrospectively collected data from patients with stage II-III colon cancer admitted to our hospital from 2017 to 2021, including 198 patients in the training cohort and 50 patients in the validation cohort. Inflammatory-nutritional indicators and body composition were included in the univariate and multivariate analyses. Binary regression was used to develop a nomogram and evaluate its predictive value. In the multivariate analysis, the monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), nutritional risk score (NRS), skeletal muscle index (SMI), and visceral fat index (VFI) were independent risk factors for postoperative complications of stage II-III colon cancer. In the training cohort, the area under the receiver operating characteristic curve of the predictive model was 0.825 (95% confidence interval [CI] 0.764-0.886). In the validation cohort, it was 0.901 (95% CI 0.816-0.986). The calibration curve showed that the prediction results were in good agreement with the observational results. Decision curve analysis showed that colon cancer patients could benefit from the predictive model. A nomogram combining MLR, SII, NRS, SMI, and VFI with good accuracy and reliability in predicting postoperative complications in patients with stage II-III colon cancer was established, which can help guide treatment decisions.

Alterations in Natural Killer Cells in Colorectal Cancer Patients with Stroma AReactive Invasion Front Areas (SARIFA).

Recently, our group introduced Stroma AReactive Invasion Front Areas (SARIFA) as an independent prognostic predictor for a poorer outcome in colon cancer patients, which is probably based on immunologic alterations combined with a direct tumor-adipocyte interaction: the two together reflecting a distinct tumor biology. Considering it is already known that peripheral immune cells are altered in colorectal cancer (CRC) patients, this study aims to investigate the changes in lymphocyte subsets in SARIFA-positive cases and correlate these changes with the local immune response. Flow cytometry was performed to analyze B, T, and natural killer (NK) cells in the peripheral blood (PB) of 45 CRC patients. Consecutively, lymphocytes in PB, tumor-infiltrating lymphocytes (TILs), and CD56+ and CD57+ lymphocytes at the invasion front and the tumor center were compared between patients with SARIFA-positive and SARIFA-negative CRCs. Whereas no differences could be observed regarding most PB lymphocyte populations as well as TILs, NK cells were dramatically reduced in the PB of SARIFA-positive cases. Moreover, CD56 and CD57 immunohistochemistry suggested SARIFA-status-dependent changes regarding NK cells and NK-like lymphocytes in the tumor microenvironment. This study proves that our newly introduced biomarker, SARIFA, comes along with distinct immunologic alterations, especially regarding NK cells.

Omics sciences and precision medicine in colon cancer.

Colon cancer presents a complex pathophysiological landscape, which poses a significant challenge to the precise prediction of patient prognosis and treatment response. However, the emergence of omics sciences such as genomics, transcriptomics, proteomics, and metabolomics has provided powerful tools to identify molecular alterations and pathways involved in colon cancer development and progression. To address the lack of literature exploring the intersection of omics sciences, precision medicine, and colon cancer, we conducted a comprehensive search in ScienceDirect and PubMed databases. We included systematic reviews, reviews, case studies, clinical studies, and randomized controlled trials that were published between 2015-2023. To refine our search, we excluded abstracts and non-English studies. This review provides a comprehensive summary of the current understanding of the latest developments in precision medicine and omics sciences in the context of colon cancer. Studies have identified molecular subtypes of colon cancer based on genomic and transcrip-tomic profiles, which have implications for prognosis and treatment selection. Furthermore, precision medicine (which involves tailoring treatments, based on the unique molecular characteristics of each patient's tumor) has shown promise in improving outcomes for colon cancer patients. Omics sciences and precision medicine hold great promise for identifying new therapeutic targets and developing more effective treatments for colon cancer. Although not strictly designed as a systematic review, this review provides a readily accessible and up-to-date summary of the latest developments in the field, highlighting the challenges and opportunities for future research.

The usefulness of indocyanine green fluorescence imaging for intestinal perfusion assessment of intracorporeal anastomosis in laparoscopic colon cancer surgery.

The purpose of this study was to clarify the usefulness of indocyanine green fluorescence imaging (ICG-FI) in the assessment of intestinal vascular perfusion in patients who receive intracorporeal anastomosis (IA) in colon cancer surgery. This was a single-center, retrospective study using propensity score matching. We compared the surgical outcomes of colon cancer patients who underwent laparoscopic colonic resection with IA or external anastomosis (EA) with the intraoperative evaluation of anastomotic perfusion using ICG-FI from January 2019 to July 2021. The detection rate of poor anastomotic perfusion by ICG-FI was examined. A total of 223 patients were enrolled. After matching, 69 patients each were classified into the IA and EA groups. There were no significant differences in age, sex, body mass index, tumor localization, or progression between the two groups. The operation time was similar (172min vs. 171min, p = 0.62) and the amount of bleeding was significantly lower (0ml vs. 2ml, p = 0.0023) in the IA group. The complication rates (grade ≥ 2) of the two groups were similar (14.5% vs. 11.6%, p = 0.59). ICG-FI identified four patients (5.8%) with poor anastomotic perfusion in the IA group, but none in the EA group (p = 0.046). All four patients with poor perfusion in the IA group underwent additional resection; none of these patients developed postoperative complications. Poor anastomotic perfusion was detected in 5.8% of cases who underwent laparoscopic colon cancer surgery with IA. ICG-FI is useful for evaluating anastomotic perfusion in IA in order to prevent AL.

Oncological outcomes of elective versus emergency surgery for colon cancer: A tertiary academic center experience.

In this study, we aimed to identify the oncological outcomes in colon cancer patients who underwent elective versus emergency curative resection. All patients who underwent curative resection for colon cancer between July 2015 and December 2019 were retrospectively reviewed and analyzed. Patients were divided into two groups based on the presentation into elective and emergency groups. A total of 215 patients with colon cancer were admitted and underwent curative surgical resection. Of those, 145 patients (67.4%) were elective cases, and 70 (32.5%) were emergency cases. Family history of malignancy was positive in 44 patients (20.5%) and significantly more common in the emergency group (P = 0.016). The emergency group had higher T and TNM stages (P = 0.001). The 3-year survival rate was 60.9% and significantly less in the emergency group (P = 0.026). The mean duration from surgery to recurrence, 3-year disease-free survival, and overall survival were 1.19, 2.81, and 3.11, respectively. Elective group was associated with better 3-year survival, longer overall, and 3-year disease-free survival compared to the emergency group. The disease recurrence rate was comparable in both groups, mainly in the first two years after curative resection.

SJLA_2024_A3: Oncological Outcomes of Elective versus Emergency Surgery for Colon Cancer: A Tertiary Academic Center Experience

Background: In this study, we aimed to identify the oncological outcomes in colon cancer patients who underwent elective versus emergency curative resection. Methods: All patients who underwent curative resection for colon cancer between July 2015 and December 2019 were retrospectively reviewed and analyzed. Patients were divided into two groups based on the presentation into elective and emergency groups. Results: A total of 215 patients with colon cancer were admitted and underwent curative surgical resection. Of those, 145 patients (67.4%) were elective cases, and 70 (32.5%) were emergency cases. Family history of malignancy was positive in 44 patients (20.5%) and significantly more common in the emergency group (P = 0.016). The emergency group had higher T and TNM stages (P = 0.001). The 3-year survival rate was 60.9% and significantly less in the emergency group (P = 0.026). The mean duration from surgery to recurrence, 3-year disease-free survival, and overall survival were 1.19, 2.81, and 3.11, respectively. Conclusion: The elective group was associated with better 3-year survival, longer overall, and 3-year disease-free survival compared to the emergency group. The disease recurrence rate was comparable in both groups, mainly in the first 2 years after curative resection.

Incidence, predictors and prognostic implications of positive circumferential resection margin in colon cancer: A retrospective study in a Chinese high-volume cancer center.

Positive circumferential resection margin (CRM) was associated with a higher recurrence rate and worse survival in rectal cancer. Predictors of CRM in rectal cancer have widely been investigated. Our study aims to determine the incidence, predictors and prognostic implications of positive CRM following colon cancer (CC) surgery in a Chinese high-volume cancer center. The clinicopathological features and oncological outcomes of CC patients undergoing surgery between January 2008 and December 2018 were identified from Fudan University Shanghai Cancer Center database. Positive CRM was defined as resection margin ≤1 mm. A total of 5268 stage I-IV CC patients were identified in our study, 108 (2.05%) of whom had positive CRM. Multivariate logistic analysis found that advanced N stage, distant metastases and poorly differentiated tumor had increased risk of positive CRM. After propensity score matching, the 5-year overall survival rates of the patients with positive and negative CRM were 33.2% and 39.8% (P=0.005), respectively. Multivariable COX regression model showed that positive CRM was an independent prognostic factor for OS in CC patients. The overall rate of positive CRM in our center is lower than that in western population. Several adverse pathological parameters deserve more attention to identify CC patients at a high risk of positive CRM. Adoption of appropriate surgical techniques and multidisciplinary treatment planning are expected to improve oncological outcomes for high selected CC patients with “high-risk” CRM involvement.

Integration of Bulk and Single-Cell RNA-Seq Data to Construct a Prognostic Model of Membrane Tension-Related Genes for Colon Cancer.

Background: The plasma membrane provides a highly dynamic barrier for cancer cells to interact with their surrounding microenvironment. Membrane tension, a pivotal physical property of the plasma membrane, has attracted widespread attention since it plays a role in the progression of various cancers. This study aimed to identify a prognostic signature in colon cancer from membrane tension-related genes (MTRGs) and explore its implications for the disease. Methods: Bulk RNA-seq data were obtained from The Cancer Genome Atlas (TCGA) database, and then applied to the differentially expressed gene analysis. By implementing a univariate Cox regression and a LASSO-Cox regression, we developed a prognostic model based on four MTRGs. The prognostic efficacy of this model was evaluated in combination with a Kaplan–Meier analysis and receiver operating characteristic (ROC) curve analysis. Moreover, the relationships between the signature and immune cell infiltration, immune status, and somatic mutation were further explored. Lastly, by utilizing single-cell RNA-seq data, cell type annotation, pseudo-time analysis, drug sensitivity, and molecular docking were implemented. Results: We constructed a 4-MTRG signature. The risk score derived from the model was further validated as an independent variable for survival prediction. Two risk groups were divided based on the risk score calculated by the 4-MTRG signature. In addition, we observed a significant difference in immune cell infiltration, such as subsets of CD4 T cells and macrophages, between the high- and low-risk groups. Moreover, in the pseudo-time analysis, TIMP1 was found to be more highly expressed with the progression of time. Finally, three small molecule drugs, elesclomol, shikonin, and bryostatin-1, exhibited a binding potential to TIMP-1. Conclusions: The novel 4-MTRG signature is a promising biomarker in predicting clinical outcomes for colon cancer patients, and TIMP1, a member of the signature, may be a sensitive regulator of the progression of colon cancer.

The impact of a multispecialty operative team on colorectal cancer surgery: A retrospective study from a would-be medical center in Taiwan.

Some studies showed that when distant metastasis or locally advanced tumors were observed, the participation of 2 or more operating surgeons (combined surgery) in the operation could improve the prognosis of patients. The multispecialty operative team would perform combined surgery in colon cancer patients with some complications since 2015.The goal of this study is to confirm performing combined surgery would improve the outcomes of colon cancer patients.A retrospective observational study was conducted, which involved all colon cancer patients between November 2015 and December 2019 at one would-be medical center. Patients were divided into 3 cohorts: those with complicated cases and had combined surgery (C_2S), those with complicated cases and had surgery performed by a single surgeon (C_1S), and those with uncomplicated cases and had surgery performed by a single surgeon (NC_1S). Overall survival and disease-free survival were compared among the 3 groups.A total of 296 colon cancer patients during the study period. Among them, 35 were C_2S, 87 were C_1S, and 174 were NC_1S. Patients in the NC_1S group had significantly higher 12-, 24-, and 36-month OS rates compared to those in the C_1S group (P < .01). In contrast, there was no significant difference in overall survival among patients in the NC_1S and C_2S group (P =.15).The quality of surgery must be impact the prognosis, especially in the individual who was complicated case, the survival in patients who had surgery performed by multispecialty operative team would be improved.

A Systematic Framework for Identifying Prognostic Genes in the Tumor Microenvironment of Colon Cancer.

As one of the most common cancers of the digestive system, colon cancer is a predominant cause of cancer-related deaths worldwide. To investigate prognostic genes in the tumor microenvironment of colon cancer, we collected 461 colon adenocarcinoma (COAD) and 172 rectal adenocarcinoma (READ) samples from The Cancer Genome Atlas (TCGA) database, and calculated the stromal and immune scores of each sample. We demonstrated that stromal and immune scores were significantly associated with colon cancer stages. By analyzing differentially expressed genes (DEGs) between two stromal and immune score groups, we identified 952 common DEGs. The significantly enriched Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for these DEGs were associated with T-cell activation, immune receptor activity, and cytokine–cytokine receptor interaction. Through univariate Cox regression analysis, we identified 22 prognostic genes. Furthermore, nine key prognostic genes, namely, HOXC8, SRPX, CCL22, CD72, IGLON5, SERPING1, PCOLCE2, FABP4, and ARL4C, were identified using the LASSO Cox regression analysis. The risk score of each sample was calculated using the gene expression of the nine genes. Patients with high-risk scores had a poorer prognosis than those with low-risk scores. The prognostic model established with the nine-gene signature was able to effectively predict the outcome of colon cancer patients. Our findings may help in the clinical decisions and improve the prognosis for colon cancer.

Surgical Outcomes in Patients With Preoperative Anemia Undergoing Colectomy for Colon Cancer.

Preoperative anemia is relatively common in colon cancer patients; however, its impact on short-term surgical outcomes is not well established. The aim of our study was to evaluate short-term surgical outcomes in colon cancer patients with preoperative anemia undergoing colectomy. We performed a 4-year analysis of the ACS-NSQIP and included all adult patients who underwent colectomy for colon cancer. Patients were stratified into two groups based on preoperative anemia (Preop Anemia, No Preop Anemia). Our outcome measures were 30-day complications, 30-day unplanned readmissions, and 30-day mortality. A total of 35,243 colon cancer patients who underwent colectomy were included in the analysis, of whom 50.4% had preoperative anemia. The mean age was 65±13years and the mean hemoglobin level was 12±2g/dL. Patients in the anemia group were more likely to be African American, have higher ASA class ≥3, and were more likely to receive at least 1 unit of packed red blood cells preoperatively (7.1% versus 0.3%, P<0.01). Patients in the anemia group had higher rates of 30-day complications (34.5% versus 16.6%, P<0.01), 30-day readmission related to the principal procedure (11.7% versus 8.7%, P<0.01), and 30-day mortality (3.1% versus 1%, P<0.01). On regression analysis, preoperative anemia was independently associated with higher odds of 30-day complications (P<0.01), but not 30-day readmission, or 30-day mortality (P=0.464 and P=0.362 respectively). Preoperative anemia appears to be associated with postoperative complications. Preoperatively optimizing hemoglobin levels may lead to improved outcomes.