Indicator In Colorectal Cancer Research Articles

Role of Verhoeff’s Elastic Stain to Detect Venous Invasion in Colorectal Adenocarcinoma

Background: Venous invasion is not only an important prognostic indicator in colorectal cancer, but also an important factor of deciding treatment plan for adjuvant therapy. Vascular invasion is usually assessed using hematoxylin and eosin (H & E). But the accuracy of detection of venous invasion using H & E is debatable. Verhoeff's elastic stain is a staining protocol used to demonstrate normal or pathologic elastic fibers, which can be used to improve the detection of venous invasion. Objectives: To evaluate the role of Verhoeff’s elastic stain to detect venous invasion in colorectal adenocarcinoma. Methods: This was a cross-sectional study carried out among 91 cases of colorectal adenocarcinoma. The duration for this study was from March, 2020 to February, 2022. Demographic and histopathological variables were assessed. Venous invasion with both H& E and Verhoeff’s stains were evaluated. Results: Mean age was 51.7 ± 10.9 years. The majority of the patients were males (61.5%). The most common site of the tumor was colon (74.7%). Tumors having size ≥5 cm in diameter (71.4%) were more common. Majority (78.0%) were found to be moderately differentiated neoplasm by histological grading. The rate of venous invasion detection was higher with Verhoeff’s elastic stain compared to H & E stain. Positive results for venous invasion were observed in 21 (23.1%) and 40 (44.0%) cases stained with H & E and Verhoeff’s elastic stain, respectively. Conclusion: This study found that Verhoeff's elastic stain is better at detecting venous invasion in colorectal adenocarcinoma than H&E stain. Therefore, Verhoeff's elastic stain can be routinely employed to detect venous invasion in resected samples of colorectal carcinoma.

Exploring prognostic biomarkers in pathological images of colorectal cancer patients via deep learning.

Hematoxylin and eosin (H&E) whole slide images provide valuable information for predicting prognostic outcomes in colorectal cancer (CRC) patients. However, extracting prognostic indicators from pathological images is challenging due to the subtle complexities of phenotypic information. We trained a weakly supervised deep learning model on data from 640 CRC patients in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial dataset and validated it using data from 522 CRC patients in the cancer genome atlas (TCGA) dataset. We created the colorectal cancer risk score (CRCRS) to assess patient prognosis, visualized the pathological phenotype of the risk score using Grad-CAM, and employed multiomics data from the TCGA CRC cohort to investigate the potential biological mechanisms underlying the risk score. The overall survival analysis revealed that the CRCRS served as an independent prognostic indicator for both the PLCO cohort (p < 0.001) and the TCGA cohort (p < 0.001), with its predictive efficacy remaining unaffected by the clinical staging system. Additionally, satisfactory chemotherapeutic benefits were observed in stage II/III CRC patients with high CRCRS but not in those with low CRCRS. A pathomics nomogram constructed by integrating the CRCRS with the tumor-node-metastasis (TNM) staging system enhanced prognostic prediction accuracy compared with using the TNM staging system alone. Noteworthy features of the risk score were identified, such as immature tumor mesenchyme, disorganized gland structures, small clusters of cancer cells associated with unfavorable prognosis, and infiltrating inflammatory cells associated with favorable prognosis. The TCGA multiomics data revealed potential correlations between the CRCRS and the activation of energy production and metabolic pathways, the tumor immune microenvironment, and genetic mutations in APC, SMAD2, EEF1AKMT4, EPG5, and TANC1. In summary, our deep learning algorithm identified the CRCRS as a prognostic indicator in CRC, providing a significant approach for prognostic risk stratification and tailoring precise treatment strategies for individual patients.

Clinicopathological and molecular differences between stage IV screen-detected and interval colorectal cancers in the Flemish screening program.

Interval cancer (IC) is an important quality indicator in colorectal cancer (CRC) screening. Previously, we found that fecal immunochemical test (FIT) ICs are more common in women, older age, right-sided tumors, and advanced stage. Here, we extended our existing stage IV patient cohort with clinicopathological and molecular characteristics, to identify factors associated with FIT-IC. Logistic regression models were fit to identify variables associated with the odds of having a stage IV FIT-IC. Multivariate models were corrected for gender, age, and location. A total of 292 screen-detected (SD) CRCs and 215 FIT-IC CRCs were included. FIT-IC CRC had 5 fold higher odds to be a neuroendocrine (NET) tumor and 2.5 fold higher odds to have lymphovascular invasion. Interestingly, some variables lost significance upon accounting for location. Thus, tumor location is a critical covariate that should always be included when evaluating factors related to FIT-IC. We identified NETs and lymphovascular invasion as factors associated with increased odds of having a stage IV FIT-IC. Moreover, we highlight the importance of tumor location as a covariate in evaluating FIT-IC related factors. More research across all stages is needed to clarify how these insights might help to optimize the Flemish CRC screening program.

Establishing Criteria for Tumor Necrosis as Prognostic Indicator in Colorectal Cancer.

Tumor necrosis has been reported to represent an independent prognostic factor in colorectal cancer, but its evaluation methods have not been described in sufficient detail to introduce tumor necrosis evaluation into clinical use. To study the potential of tumor necrosis as a prognostic indicator in colorectal cancer, criteria for 3 methods for its evaluation were defined: the average percentage method (tumor necrosis percentage of the whole tumor), the hotspot method (tumor necrosis percentage in a single hotspot), and the linear method (the diameter of the single largest necrotic focus). Cox regression models were used to calculate cancer-specific mortality hazard ratios (HRs) for tumor necrosis categories in 2 colorectal cancer cohorts with more than 1800 cases. For reproducibility assessment, 30 cases were evaluated by 9 investigators, and Spearman's rank correlation coefficients and Cohen's kappa coefficients were calculated. We found that all 3 methods predicted colorectal cancer-specific survival independent of other prognostic parameters, including disease stage, lymphovascular invasion, and tumor budding. The greatest multivariable HRs were observed for the average percentage method (cohort 1: HR for ≥ 40% vs. <3% 3.03, 95% CI, 1.93-4.78; cohort 2: HR for ≥ 40% vs. < 3% 2.97; 95% CI, 1.63-5.40). All 3 methods had high reproducibility, with the linear method showing the highest mean Spearman's correlation coefficient (0.91) and Cohen's kappa (0.70). In conclusion, detailed criteria for tumor necrosis evaluation were established. All 3 methods showed good reproducibility and predictive ability. The findings pave the way for the use of tumor necrosis as a prognostic factor in colorectal cancer.

Assessment of ID family proteins expression in colorectal cancer of Iraqi patients.

Colorectal cancer (CRC) is the second most deathly worldwide and third most common cancer, CRC is a very heterogeneous disease where tumors can form by both environmental and genetic risk factors and includes epigenetic and genetic alternations. Inhibitors of DNA binding proteins (ID) are a class of helix-loop-helix transcription regulatory factors; these proteins are considered a family of four highly preserved transcriptional regulators (ID1-4), shown to play significant roles in many processes that are associated with tumor development. ID family plays as negatively dominant antagonists of other essential HLH proteins, concluding the creation of non-functional heterodimers and regulation of the transcription process. 120 Fresh tissue and blood samples Forty (40) samples of fresh tissue and blood were collected from patients diagnosed with CRC, twenty (20) samples were collected from a patient diagnosed as healthy. The (qRT-PCR) method is a sensitive technique for the quantifying of steady-state mRNA levels that used to evaluation the expression levels of ID (1-4) gene. The findings indicate downregulation in ID1 in tissue with a highly significant change between patients and control groups, where upregulation in the ID1 gene is shown in blood samples.ID2 gene also demonstrated high significant change where show upregulation in tissue and downregulation in blood sample. ID3 and ID4 genes show downregulation in tissue and blood samples with a significant change in ID3 blood samples between patient and blood groups. Because of the regulation function of the ID family in many processes, the up or down regulation of IDs genes in tumors Proves how important its tumor development, and therefore those proteins can be used as an indicator for CRC.

Colorectal cancer and association with anaerobic bacteraemia: A Danish nationwide population-based cohort study

We aimed to identify specific anaerobic bacteria causing bacteraemia and a subsequent diagnosis of colorectal cancer. A nationwide population-based cohort study, which included all episodes of defined specific anaerobic bacteraemia from 2010 (5,534,738 inhabitants) through 2020 (5,822,763 inhabitants) and all cases of colorectal cancer diagnosed from 2010 through 2021 in Denmark. We calculated the incidence and risk of colorectal cancer after bacteraemia with specific anaerobic bacteria using Escherichia coli bacteraemia as reference. Nationwide data on colorectal cancer and specific anaerobic bacteraemia (100% complete, representing 11,124 episodes). The frequencies of colorectal cancer within one year following anaerobic bacteraemia were higher for species, which almost exclusively reside in the colon, such as Phocaeicola vulgatus/dorei (5.5%), Clostridium septicum (24.2%), and Ruminococcus gnavus (4.6%) compared to 0.6% in 50,650 E. coli bacteraemia episodes. Bacteroides spp. had a subhazard ratio for colorectal cancer of 3.9 (95% confidence interval [CI], 3.0 to 5.1) and for Clostridium spp. it was 8.9 (95% CI, 6.7 to 11.8, with C. septicum 50.0 [95% CI, 36.0 to 69.5]) compared to E. coli (reference). This nationwide study identified specific colorectal cancer-associated anaerobic bacteria, which almost exclusively reside in the colon. Bacteraemia with these bacteria could be an indicator of colorectal cancer.

LncRNA FAM30A Predicts Adverse Prognosis and Regulates Cellular Processes in Colorectal Cancer via Modulating miR-21-3p.

Colorectal cancer (CRC) is a prevalent gastrointestinal cancer with high incidence and mortality rate. lncRNAs could regulate the expression of miRNAs and further affect cancer development. Previous research has suggested that FAM30A is involved in various cancer. We aimed to investigate the function of FAM30A in the prognosis of CRC and its underlying molecular mechanisms. Matched tissues were collected from 107 CRC patients. FAM30A was measured by quantitative real-time transcription polymerase chain reaction and its clinical significance was evaluated by its correlation with patients' prognosis and clinicopathological features. Furthermore, the dual luciferase reporter assays were employed to assess the interactions between FAM30A and miR-21-3p and to evaluate the role of miR-21-3p in regulating the tumor suppressor effects of FAM30A. Cell proliferation and metastasis were evaluated by the Transwell assay and cell counting kit-8 assay. FAM30A level was markedly decreased in CRC tissues (P <.001). A prominent association was observed in FAM30A with tumor- node-metastasis stage (P = .022), carcinoembryonic antigen (P = .027), and differentiation (P = .043) of CRC patients. The lower the FAM30A level was associated with the lower the survival rate of the CRC patients (log rank P = .034). FAM30A could negatively modulate miR-21-3p (P <.001), and the overexpression of FAM30A significantly suppressed CRC cell proliferation and metastasis (P <.001). The suppressive function of FAM30A overexpression was mediated by miR-21-3p. FAM30A can be considered a poor prognostic indicator in CRC. Decreased FAM30A can promote the proliferation and metastasis of CRC cells by negatively regulating miR-21-3p.

Prognostic scoring system based on indicators reflecting the tumor glandular differentiation and microenvironment for patients with colorectal cancer

Prognostic stratification is an urgent concern for patients with colorectal cancer (CRC). The desmoplastic reaction (DR) is speculated to mirror the tumor microenvironment. DR types are considered independent prognostic indicators in CRC, but have not been incorporated in previous prognostic nomograms. We aimed to assess the prognostic significance of a novel approach incorporating histopathological indicators reflecting tumor glandular differentiation and microenvironment. We evaluated 329 consecutive patients with CRC who underwent surgical resection at Kansai Medical University. Histological glandular differentiation was scored as 2 (0 point), 3 (1 point), or 4 (2 points). Tumor buddings (TBs) were classified as TB1 (0 point), TB2 (1 point), or TB3 (2 points). pT1 or 2 was considered as 0 point, pT3 or 4 + DR non-immature type as 1 point, and pT3 or 4 + DR immature type as 2 points. Lymph node metastasis was classified as pN0 (0 point), pN1 (1 point), or pN2 (2 points). The preoperative carcinoembryonic antigen levels were categorized as < 5.0 ng/mL (0 point) and ≧5.0 (1 point). Considering these factors, the following D&M (tumor differentiation and microenvironment) scoring system was applied: I (0–2 points), II (3–4 points), III (5–6 points), and IV (7–9 points). Kaplan–Meier curves showed significant differences in disease-specific survival and recurrence-free survival among the assigned scores, highlighting their enhanced utility compared with the American Joint Committee on Cancer 8th edition staging system. The D&M scoring system was valuable as the initial prognostic nomogram, including DR.

HTRA1 interacts with SLC7A11 to modulate colorectal cancer chemosensitivity by inhibiting ferroptosis

Chemotherapy is an important therapuetic strategy for colorectal cancer (CRC), but chemoresistance severely affects its efficacy, and the underlying mechanism has not been fully elucidated. Increasing evidence suggests that lipid peroxidation imbalance-mediated ferroptosis is closely associated with chemoresistance. Hence, targeting ferroptosis pathways or modulating the tolerance to oxidative stress might be an effective strategy to reverse tumor chemoresistance. HtrA serine protease 1 (HTRA1) was screened out as a CRC progression- and chemoresistance-related gene. It is highly expressed in CRC cells and negatively correlated with the prognosis of CRC patients. Gain- and loss-of-function analyses demonstrated a stimulatory role of HTRA1 on the proliferation of CRC cells. The enrichment analysis of HTRA1-interacting proteins indicated the involvement of ferroptosis in the HTRA1-mediated chemoresistance. Moreover, electron microscope analysis, as well as the ROS and MDA levels in CRC cells also confirmed the effect of HTRA1 on ferroptosis. We also verified that HTRA1 could interact with SLC7A11 through its Kazal structural domain and up-regulate the expression of SLC7A11, which in turn inhibited the ferroptosis and leaded to the chemoresistance of CRC cells to 5-FU/L-OHP. Hence, we propose that HTRA1 may be a potential therapeutic target and a prognostic indicator in CRC.

Abstract 276: Artificial intelligence-powered analysis of tumor-stroma ratio and fibroblast density as prognostic indicators in colorectal cancer

Abstract Introduction: The tumor microenvironment (TME) plays a critical role in cancer prognosis. In colorectal cancer (CRC), the tumor-stroma ratio (TSR) and cancer-associated fibroblast (CAF) density are emerging as prognostic markers. However, accurately quantifying them remains challenging. Recent studies have shown that artificial intelligence (AI)-powered analyzers can quantify features in the TME including these. Methods: Lunit SCOPE IO, an AI-powered H&amp;E whole-slide image analyzer that detects fibroblasts and segments cancer area and stromal area, was applied to evaluate TSR and CAF density in treatment-naive, stage II or III CRC surgical specimens (N = 207) from Severance Hospital. TSR was calculated as the ratio of the area of the cancer area (CA) to the sum of the CA and the cancer stromal area (CS) within a slide. CAF density was evaluated as the fibroblast density within the CA or CS, or the ratio between them. Cox survival analysis determined the hazard ratios (HRs) in progression-free survival (PFS) between the high/low TSR/CAF groups, defining high/low groups based on optimized hazard ratio (HR) cutoffs. Results: The study found a mean TSR of 0.481±0.126 and CAF densities of 69.96±37.53/mm² (cancer area) and 1844.29±440.31/mm² (stromal area). Higher TSR, lower CAF density in CA, and higher CAF density in CS were linked to better prognosis (Table 1). The mean CAF ratio (CAF density of CS divided by CAF density of CA) was 33.92±25.35, and a group with high values showed a favorable prognosis. Dividing patients based on TSR and CAF ratio, we found that high levels in either or both metrics predicted better outcomes compared to low levels in both. Table 1. Prognosis by tumor-stroma ratio (TSR) and cancer-associated fibroblast (CAF) density Factor Group Hazard ratio (95% confidence interval) Mean progression-free survival (months) p-value TSR (cutoff: 0.351) Low (N = 34) Reference 43.7 &amp;lt;0.001 High (N = 173) 0.32 (0.19 - 0.56) 67.2 CAF density of cancer area (CA) (cutoff: 46.8) Low (N = 62) Reference 69.3 0.056 High (N = 145) 1.86 (0.98 - 3.50) 60.7 CAF density of cancer stromal area (CS) (cutoff:1,901) Low (N = 116) Reference 58.2 0.015 High (N = 91) 0.50 (0.29 - 0.88) 69.9 The ratio of CAF density of CS to CA (CAF ratio) (cutoff: 53.1) Low (N = 187) Reference 61.5 0.043 High (N = 20) 0.13 (0.02 - 0.94) 80.9 Combination of TSR and CAF ratio Both low (N = 32) Reference 41.2 &amp;lt;0.001 TSR high, CAF ratio low (N = 155) 0.32 (0.19 - 0.56) 65.8 TSR low, CAF ratio high (N = 2) 0.00 (0.00 - ∞) 83.4 Both high (N = 18) 0.06 (0.01 - 0.45) 80.2 Conclusions: In this study, we found a favorable prognosis in the group with higher TSR or higher density of CAF in CS compared to CA. This result suggests that AI-enhanced analysis of TSR and CAF can effectively predict prognosis in CRC, highlighting the potential roles of these markers in cancer prognosis. Citation Format: Minsun Jung, Jun Yong Kim, Mingu Kang, Jinhee Lee, Sanghoon Song, Taebum Lee, Wonkyung Jung, Soo Ick Cho. Artificial intelligence-powered analysis of tumor-stroma ratio and fibroblast density as prognostic indicators in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 276.

Incorporating Novel Technologies in Precision Oncology for Colorectal Cancer: Advancing Personalized Medicine

Colorectal cancer (CRC) is one of the most heterogeneous and deadly diseases, with a global incidence of 1.5 million cases per year. Genomics has revolutionized the clinical management of CRC by enabling comprehensive molecular profiling of cancer. However, a deeper understanding of the molecular factors is needed to identify new prognostic and predictive markers that can assist in designing more effective therapeutic regimens for the improved management of CRC. Recent breakthroughs in single-cell analysis have identified new cell subtypes that play a critical role in tumor progression and could serve as potential therapeutic targets. Spatial analysis of the transcriptome and proteome holds the key to unlocking pathogenic cellular interactions, while liquid biopsy profiling of molecular variables from serum holds great potential for monitoring therapy resistance. Furthermore, gene expression signatures from various pathways have emerged as promising prognostic indicators in colorectal cancer and have the potential to enhance the development of equitable medicine. The advancement of these technologies for identifying new markers, particularly in the domain of predictive and personalized medicine, has the potential to improve the management of patients with CRC. Further investigations utilizing similar methods could uncover molecular subtypes specific to emerging therapies, potentially strengthening the development of personalized medicine for CRC patients.

MiR-373 promotes invasion and metastasis of colorectal cancer cells via activating ERK/MAPK pathway

To explore the relationship between miR-373 and the occurrence and development of colorectal cancer. Additionally, it aims to predict the potential cellular signaling pathways and regulatory mechanisms in which miR-373 may be involved and provides a theoretical basis and experimental evidence for the clinical application of miR-373 as a potential biomarker, molecular target, and prognostic indicator in colorectal cancer. Real-time quantitative PCR is used to analyze the expression of miR-373 in human colorectal cancer cell lines and normal human colonic epithelial cells. Further validation of the differential expression of miR-373 in colorectal cancer cell lines is being performed. Biological functions such as cell proliferation, invasion and apoptosis are being detected by MTT, CCK-8, transwell, cell cycle analysis, and flow cytometry experiments to verify the changes in the biological behavior of colon cancer cells after overexpression and interference of miR-373 in SW-480 cells and to explore the effects of miR-373 on cell proliferation, invasion, and apoptosis in colon cancer cells. Proteomic analysis is being conducted on proteins extracted from miR-373 overexpressing SW480 cells, and mass spectrometry is used for protein identification. GO, KEGG, and enrichment analysis are being employed to analyze the significantly differentially expressed proteins. The expression levels of pathway-related proteins are being verified using Western blot. Overexpression of miR-373 increased the invasive and metastatic ability of SW-480 cells; knockdown of miR-373 decreased the invasive and metastatic ability of SW-480 cells. However, there was no statistically significant effect on cell proliferation and apoptosis in SW-480 cells. Proteomic analysis identified 78 differentially expressed proteins based on fold change (FC) > 1.2 and P < 0.05. Annotation of differentially changed proteins revealed that the MAPK signaling pathway, PI3K-Akt signaling pathway, and FAK signaling pathway may play crucial roles in the migration and invasion of colorectal cancer. Western blot analysis showed that overexpression of miR-373 significantly increased the levels of p-ERK1/2 in SW480 cells. miR-373 may activate the ERK/MAPK signaling pathway to promote the invasion and migration of colorectal cancer cells.

Comprehensive analysis of disulfidptosis-related lncRNA features for prognosis and immune landscape prediction in colorectal cancer.

Disulfidptosis is a novel mechanism underlying actin-cytoskeleton-associated cell death, but its function in colorectal cancer (CRC) is still elusive. In this study, we investigated the potential role of Disulfidptosis-Related Long Non-Coding RNAs (DRLs) as prognostic indicators in CRC. Through transcriptome data from TCGA CRC cases, we identified 44 prognosis-correlated DRLs by Univariate Cox Regression Analysis and observed a differential expression pattern of these DRLs between CRC and normal tissues. Consensus clustering analysis based on DRL expression led to subgroup classification of CRC patients with distinct molecular fingerprints, accompanied by a superior survival outcome in cluster 2. We are encouraged to develop a score model incorporating 12 key DRLs to predict patient outcomes. Notably, this model displayed more reliable accuracy than other predictive indicators since DRLs are intimately related to tumor immune cell infiltration, suggesting a considerable potential of our DRL-score model for tumor therapy. Our data offered a valuable insight into the prognostic significance of DRLs in CRC and broke a new avenue for tumor prognosis prediction.

Long non-coding RNA FENDRR suppresses cancer-associated fibroblasts and serves as a prognostic indicator in colorectal cancer

Genetically abnormal fibroblasts are notably more prevalent in colorectal cancer (CRC) than in adjacent normal tissue, emphasizing their significance in driving the heterogeneity of the tumor microenvironment. Functioning as a significant regulatory gene in the context of fibrosis, FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) has exhibited abnormal expression in colorectal cancer and interstitial localization in our experiments. However, current research on the role of FENDRR in cancer has focused solely on its impact on cancer cells. Its crucial role in the tumor stroma is yet to be explored. The goal of this study was to understand the relationship between atypical FENDRR expression, its distinct localization, and genetically abnormal fibroblasts in CRC. We aimed to establish the function of FENDRR within the stromal compartment of patients through bioinformatics. Our study confirmed that FENDRR suppresses cancer-associated fibroblasts by inhibiting their activation and collagen generation in CRC. Furthermore, our findings suggest that low FENDRR expression indicates a poor prognosis. Therefore, we propose that FENDRR is a promising therapeutic target for future studies in CRC.

Cuproptosis-related miRNAs signature and immune infiltration characteristics in colorectal cancer.

A novel form of cell death termed cuproptosis was proposed recently. miRNAs play important roles in colorectal cancer (CRC). However, their relationships have not been reported. miRNAs that negatively regulate 16 cuproptosis regulators were predicted using Targetscan database. The univariate Cox, LASSO, and multivariate Cox regression analyses were performed to select cuproptosis-related miRNAs. GSEA and ssGSEA analysis was carried out for functional enrichment analysis. The immune cell proportion score (IPS) and the efficiencies of multiple chemotherapy drugs were compared between different risk groups. The CCK8, cell colony, edu, and flow cytometry assays were performed to validate the roles of miRNA. Luciferase reporter assay confirmed the regulatory mechanism of miRNA on cuproptosis. Six cuproptosis-related miRNAs (hsa-miR-653, hsa-miR-216a, hsa-miR-3684, hsa-miR-4437, hsa-miR-641, and hsa-miR-552) were screened out for model construction. The risk score could act as an independent prognostic indicator in CRC (p < 0.001, 95% HR = 1.243 (1.129-1.369)). The nomogram could efficiently predict the overall survival rate (AUC = 0.836). Then, the level of immunosuppressive pathways, immunosuppressive cells, stromal-activated genes, and stromal score was higher in the high-risk group. The IPS analysis showed a better response to immunotherapy in the low-risk group. Also, the risk score was closely correlated with efficiencies of multiple chemotherapy drugs. Furthermore, miR-653 was highly expressed in CRC tissues (p < 0.001), closely correlated with T stage (p < 0.001), metastasis (p < 0.001), and tumor stage (p < 0.001). High expression of miR-653 predicted a shorter overall survival (p = 0.0282) and disease-free survival (p = 0.0056). In addition, miR-653 promoted cell proliferation, inhibited apoptosis, and negatively regulated the expression of DLD through directly binding to the 3'-UTR of DLD mRNA. We constructed a cuproptosis-related miRNA signature for the prediction of CRC patient survival and immunotherapy sensitivity. miR-653 was highly expressed in CRC tissues, promoted cell proliferation, and inhibited apoptosis by negatively regulating the expression of DLD.

Prognostic impact of increased lymph node yield in colorectal cancer patients with synchronous liver metastasis: a population-based retrospective study of the US database and a Chinese registry.

The National Quality Forum has endorsed at least 12 lymph node yield (LNY) as a surgical quality indicator in colorectal cancer (CRC), but the prognostic value of adequate lymphadenectomy has rarely been investigated for CRC patients with distant metastatic disease. A total of 4575 CRC patients with synchronous liver metastasis who underwent primary tumor resection were identified from a Chinese registry and the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. The Kaplan-Meier methods and Cox regression models were performed to assess the correlations between LNY and 3-year cancer-specific survival (CSS). Propensity score matching were used to confirmed the survival comparison between patients with less than 12 and of at least 12 LNY. The retrieval of at least 12 LNY was identified in most CRC patients (SEER database, 3380/3899, 86.7%; Chinese cohort, 565/676, 83.6%). In both the SEER database and the Chinese cohort, the patients with LNY ≥12 was significantly associated with better CSS compared with patients with LNY <12 before and after propensity score matching, with all P -value less than 0.05. After controlling for the confounders, multivariate analysis demonstrated that LNY was also an independent prognostic factor for patients with distant metastasis in both cohorts. In subgroup analysis, the CSS benefit for patients with LNY ≥12 was observed across most of the subgroups. Clinical feasibility of the 12-node threshold as a guideline quality metric of cancer care for CRC patients is necessary, and an oncologically adequate lymphadenectomy is still a critical component of high-quality surgical standard in CRC patients with distant metastases.

Prognostic Value of Lymphocyte-to-Monocyte Ratio and Neutrophil-to-Lymphocyte Ratio in Patients with Colorectal Cancer: "A Retrospective Cohort Study"

Background: In the past decade, advancements in the treatment of colorectal cancer (CRC) have greatly improved survival; nevertheless, simple biomarkers to predict responsiveness to therapy or survival that seem relevant to all medical oncology settings globally have yet to be developed. The neutrophil/lymphocyte ratio (NLR) and the lymphocyte-to-monocyte ratio (LMR) are two simple and generally accessible examples of inflammation markers based on differential white cell counts. Methods: LMR and NLR were evaluated in 69 patients diagnosed with CRC and received different treatment approaches depending on the stage, ECOG, and treatment guidelines. The correlation between LMR and clinical pathology was retrospectively evaluated. The predicted values of NLR and compared the predicted values of LMR and NLR were also assessed. Results: After analyzing the receiver operating characteristic (ROC) curve, the cut-off level for LMR and NLR was determined to be 2. Out of the total patients, 55 (79.7%) were classified into the high LMR group, while 14 (20.3%) were categorized into the low LMR group. Among the patients, 30 (43.5%) and 39 (56.5%) were grouped into low and high NLR groups, respectively. It was concluded that tumor markers (CEA) (p 0.031), TNM staging (p=0.016), distant metastasis (p=0.014), and disease progression (p=0.038) were significant. NLR was significant in only tumor markers (p=0.014) and tumor location (p=0.046). OS was significant. Conclusion: The results indicate that prior to treatment, both LMR and NLR were significant independent predictors in colon cancer and that incorporating NLR/LMR alongside TNM staging may enhance prognostic evaluation in patients with colon cancer. However, the study was limited by a retrospective methodology and a relatively small sample size. To determine the exact cut-off values for NLR and LMR as prognostic indicators in colorectal cancer, larger-scale prospective studies involving multiple centers will be required.

Combined preoperative prognostic nutritional index and D-dimer score predicts outcome in colorectal cancer

BackgroundThe prognostic nutritional index (PNI) and D-dimer (DD) levels represent useful prognostic indicators in colorectal cancer (CRC); however, a combination of these indicators, namely, the PNI and DD score (PDS) was less addressed.MethodsA retrospective study with 183 patients after curative surgery was conducted. Patients were divided into 3 subgroups: PDS 0, decreased PNI and increased DD levels; PDS 1, decreased or increased PNI and DD levels; PDS 2, increased PNI and decreased DD levels. The differences in disease-free survival (DFS) and overall survival (OS) were compared among these subgroups, and risk factors for outcome were determined.ResultsA total of 56, 65 and 62 patients were assigned to the PDS 0, 1 and 2 subgroups, respectively. PDS was significant in predicting both the DFS (area under the curve (AUC) = 0.68, P < 0.001) and OS (AUC = 0.74, P < 0.001). PDS 0 patients were more likely to be associated with old age (P = 0.032), laparotomy (P < 0.001), elevated CEA (P = 0.001), T3 + T4 (P = 0.001) and advanced TNM stage (P = 0.031). PDS 0 patients had significantly inferior DFS (log rank = 18.35, P < 0.001) and OS (log rank = 28.34, P < 0.001) than PDS 1 or 2 patients. PDS was identified as an independent risk factor for both DFS (PDS 1: HR = 0.54, 95% CI: 0.30–1.00, P = 0.049; PDS 2: HR = 0.40, 95% CI: 0.20–0.79, P = 0.009) and OS (PDS 1: HR = 0.44, 95% CI: 0.22–0.88, P = 0.020; PDS 2: HR = 0.17, 95% CI: 0.06–0.45, P < 0.001).ConclusionThe PDS is a useful prognostic indicator for CRC patients after curative surgery, and PDS 0 patients have inferior survival. Additional future studies are needed to validate these findings.

Preoperative low absolute lymphocyte count to fibrinogen ratio correlated with poor survival in nonmetastatic colorectal cancer

BackgroundPreoperative absolute lymphocyte count (LC) and fibrinogen (FIB) are useful prognostic indicators in colorectal cancer (CRC). However, the prognostic value of the LC to FIB ratio (LFR) has never been addressed.MethodsA total of 189 nonmetastatic CRC patients after resection were enrolled retrospectively. The significance of the LFR in predicting disease-free survival (DFS) and overall survival (OS) was estimated by receiver operating characteristic curve analysis, and the prognostic efficacy was compared with individual LC and FIB. Patients were assigned to LFR low or high subgroups. Differences in clinicopathological features among these subgroups were calculated, and the survival differences of these subgroups were determined by the Kaplan-Meier analysis. A Cox proportional hazards model was applied to test the risk factors for survival.ResultsTaking 0.54 as the optimal cutoff point, the LFR had sensitivities of 79.70% and 86.40% and specificities of 52.30% and 51.00% in predicting the DFS and OS, respectively. A total of 109/189 (57.67%) patients were assigned to the LFR low group, and these patients were more likely to be characterized by criteria such as T3 + T4 (P < 0.01), stage 3 (P < 0.01), tumor deposits (P = 0.01), high CEA (P < 0.01), or CA19-9 levels (P = 0.04). And they also displayed worse DFS (log rank = 18.57, P < 0.01) and OS (log rank = 20.40, P < 0.01) than the high LFR group. Finally, the LFR was independently associated with inferior DFS (HR = 0.32, 95% CI: 0.16–0.61, P < 0.01) and OS (HR = 0.23, 95% CI: 0.09–0.55, P < 0.01).ConclusionsThe LFR is a useful prognostic indicator in nonmetastatic CRC, and patients with a relatively low LFR had poor survival.

Lactate: A regulator of immune microenvironment and a clinical prognosis indicator in colorectal cancer.

Lactate can play an immunosuppressive role in the tumor microenvironment and promote tumor development by recruiting and inducing the activity of immunosuppressive cells and molecules. High lactate concentrations are important for tumor cell metastasis, angiogenesis, and treatment resistance. With the in-depth studies on tumor metabolism, lactate, one of the key factors involved in glycolysis, has been increasing emerged its characteristic clinical value in colorectal cancer (CRC). In this study, lactate genes were screened based on lactate metabolism pathways. Subsequently, the lactate subtypes were determined by clustering and analysis of the subtypes at all levels, including immune checkpoints, immune infiltration, and clinical characteristics, which revealed the biological significance of lactate metabolism in CRC. Subtype-based differential gene analysis resulted in a lactate score, which stratifies the prognosis of CRC. We discovered that 27 lactate genes and 61 lactate-phenotype genes are associated with immune cell infiltration and have a significant prognostic efficacy. The CRC patients were clustered into four subtypes and five clusters, based on lactate genes and lactate-phenotype genes, respectively. There are significant differences in survival time and activities of hallmark pathways, namely immune-related signatures and chemokines, among these subtypes and clusters. Particularly, cluster 2 and subtype 1 have significantly higher lactate scores than that of the others. In conclusion, lactate score is an independent prognostic factor for cancer that can be used as a clinical guide for predicting CRC progression and as an evaluation factor for the effect of immunotherapy in CRC.