Prognostic Indicator In Colorectal Cancer Research Articles

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.

MiR‑25‑3p serves as an oncogenic in colorectal cancer cells by regulating the ubiquitin ligase FBXW7 function.

Accumulating evidence indicates that the dysregulation of microRNAs (miRNAs or miRs), is associated with human malignancies and suggests a casual role of miRNAs in tumor initiation and progression. Even though it has been discovered that a number of miRNAs play significant parts in the development of colorectal cancer (CRC), it is crucial to comprehend the regulatory functions that other miRNAs play in CRC. Based on GSE183437 and GSE156719 microarray data that were obtained from Gene Expression Omnibus database, candidate miRNAs were researched. The oncogenic effects of miR‑25‑3p in different malignancies have led to its selection for additional investigation in the present study. The expression of miR‑25‑3p was verified by reverse transcription‑quantitative PCR, and its correlation with clinicopathological characteristics in patients with CRC was then investigated. In vitro assays were conducted to investigate the influence of miR‑25‑3p on the proliferative and apoptotic behaviors of HCT116 and Caco‑2 cells. The present data revealed that miR‑25‑3p exhibited one of the most significant upregulations in CRC tissues and cell lines. The expression levels of miR‑25‑3p were found to be intimately correlated with tumor size, distant metastasis, tumor‑node‑metastasis stage, and shorter overall survival rate. In terms of functionality, the downregulation of miR‑25‑3p led to the inhibition of cellular proliferation and the enhancement of apoptosis in both HCT116 and Caco‑2 cell lines. The critical tumor suppressor F‑box and WD repeat containing domain 7 (FBXW7) was identified as a direct molecular target for miR‑25‑3p, with an inverse relationship observed between the two in neoplastic tissues. Subsequent studies demonstrated that the tumor suppressive effects of miR‑25‑3p inhibitor were effectively negated by the silencing of FBXW7. Moreover, the ability of FBXW7 to inhibit the expression of several oncogenes was deemed essential for countering the anticancer effects mediated by miR‑25‑3p downregulation. These findings posit miR‑25‑3p as a promising therapeutic target and prognostic indicator for CRC.

Cathepsin V is a useful prognostic factor for colorectal cancer

Molecular studies have identified various treatment-related prognostic molecules to enhance the effectiveness of colorectal cancer (CRC) treatment and improve survival rates. The expression of cathepsin V in gastrointestinal cancer cells prompted an investigation into its potential as a prognostic indicator for CRC. The evaluation of cathepsin V expression and its clinicopathological significance was conducted through immunohistochemistry in a tissue microarray, encompassing 142 CRC and normal colorectal tissues. Overall and disease-free survival rates, based on cathepsin V expression levels, were assessed using the Kaplan–Meier method and compared utilizing the log-rank test. Univariate and multivariate analyses, employing a Cox proportional hazards model, were performed to identify prognostic factors. Cathepsin V expression exhibited no correlation with age, sex, tumor location, tumor size, or histological grade. However, it was significantly correlated with depth of tumor invasion, regional lymph node (LN) metastasis, distant metastasis, and lymphovascular involvement (all p<0.001). Overall and disease-free survival rates were significantly better with low cathepsin V expression than with high expression (p<0.001). Univariate analysis identified several prognostic factors, including histological grade (low vs. high), tumor size (≤ vs. >5 cm), tumor depth (T1 vs. ≥T2), regional LN metastasis, distant metastasis, tumor-node-metastasis (TNM) stage (Stage I vs ≥II), lymphovascular involvement, and cathepsin V expression. Multivariate analysis revealed that tumor depth, distant metastasis, and cathepsin V expression are independent predictors of poor survival. Cathepsin V is frequently expressed in CRC, and its high expression is associated with poor prognosis. Therefore, cathepsin V is a useful prognostic marker for CRC.

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.

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.

The feedback loop of EFTUD2/c-MYC impedes chemotherapeutic efficacy by enhancing EFTUD2 transcription and stabilizing c-MYC protein in colorectal cancer

BackgroundChemoresistance presents a significant obstacle in the treatment of colorectal cancer (CRC), yet the molecular basis underlying CRC chemoresistance remains poorly understood, impeding the development of new therapeutic interventions. Elongation factor Tu GTP binding domain containing 2 (EFTUD2) has emerged as a potential oncogenic factor implicated in various cancer types, where it fosters tumor growth and survival. However, its specific role in modulating the sensitivity of CRC cells to chemotherapy is still unclear.MethodsPublic dataset analysis and in-house sample validation were conducted to assess the expression of EFTUD2 in 5-fluorouracil (5-FU) chemotherapy-resistant CRC cells and the potential of EFTUD2 as a prognostic indicator for CRC. Experiments both in vitro, including MTT assay, EdU cell proliferation assay, TUNEL assay, and clone formation assay and in vivo, using cell-derived xenograft models, were performed to elucidate the function of EFTUD2 in sensitivity of CRC cells to 5-FU treatment. The molecular mechanism on the reciprocal regulation between EFTUD2 and the oncogenic transcription factor c-MYC was investigated through molecular docking, ubiquitination assay, chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, and co-immunoprecipitation (Co-IP).ResultsWe found that EFTUD2 expression was positively correlated with 5-FU resistance, higher pathological grade, and poor prognosis in CRC patients. We also demonstrated both in vitro and in vivo that knockdown of EFTUD2 sensitized CRC cells to 5-FU treatment, whereas overexpression of EFTUD2 impaired such sensitivity. Mechanistically, we uncovered that EFTUD2 physically interacted with and stabilized c-MYC protein by preventing its ubiquitin-mediated proteasomal degradation. Intriguingly, we found that c-MYC directly bound to the promoter region of EFTUD2 gene, activating its transcription. Leveraging rescue experiments, we further confirmed that the effect of EFTUD2 on 5-FU resistance was dependent on c-MYC stabilization.ConclusionOur findings revealed a positive feedback loop involving an EFTUD2/c-MYC axis that hampers the efficacy of 5-FU chemotherapy in CRC cells by increasing EFTUD2 transcription and stabilizing c-MYC oncoprotein. This study highlights the potential of EFTUD2 as a promising therapeutic target to surmount chemotherapy resistance in CRC patients.

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 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.

Prognostic significance of the Naples prognostic score in colorectal cancer patients undergoing curative resection: a propensity score matching analysis

BackgroundSystemic inflammation is recognized as a hallmark of cancer that contributes to tumor development and progression in various malignancies. The Naples prognostic score (NPS) was established as a prognostic indicator for colorectal cancer (CRC). This study aims to examine the predictive value of the NPS for survival in CRC patients undergoing curative resection by a propensity score matching (PSM) analysis.MethodsA total of 533 CRC patients were enrolled in this study. Overall survival (OS) and disease-free survival (DFS) were compared between high-NPS and low-NPS groups. A time-dependent receiver operator characteristic (ROC) curve analysis was conducted to calculate the area under curve (AUC) of the NPS for OS. A multivariable Cox-proportional hazards regression analysis and PSM analysis were used to identify independent prognostic factors for OS and DFS. We compared the predictive value of the NPS to that of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), Onodera prognostic nutritional index (PNI), and controlling nutritional status score (CONUT) for OS.ResultsHigh-NPS was significantly associated with worse OS and DFS. After PSM, 123 patients were included in each group. A multivariate analysis revealed that Age ≥ 68, ASA-PS ≥ 3, high NPS and undifferentiated tumor type were independently associated with OS, while high NPS, advanced T and N stage were independently associated with DFS after PSM. The NPS had the greatest AUC for OS in comparison to the NLR, LMR, PNI and CONUT.ConclusionsWe successfully validated the prognostic utility of the NPS for CRC patients after curative resection.

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.

Preoperative Absolute Lymphocyte Count to Carcinoembryonic Antigen Ratio Is a Superior Predictor of Survival in Stage I to III Colorectal Cancer.

Background:Preoperative absolute lymphocyte count (ALC) and carcinoembryonic antigen (CEA) are useful prognostic indicators in colorectal cancer (CRC); however, the role of the ALC-to-CEA ratio (LCR) has been less addressed.Methods:A total of 189 stage I to III CRC patients who underwent radical resection were enrolled retrospectively. The significance of the LCR in predicting disease-free survival (DFS) and overall survival (OS) was calculated and compared with other markers based on ALC. The DFS and OS differences among the low- and high-LCR subgroups and risk factors for the outcome were estimated by Kaplan–Meier analysis and the Cox proportional hazards model, respectively.Results:Taking 0.28 as the cutoff point, the LCR has a sensitivity and a specificity of 75.60% and 77.00%, respectively, in predicting OS. The prognostic efficacy of LCR was significantly superior to that of other markers based on ALC for predicting DFS and OS. A total of 34.92% (66/189) of patients displayed a low LCR (<0.28), and these patients were more likely to present poor cell differentiation (P = .03), tumor deposits (P < .01) and advanced T (P < .01) and liver metastasis (P = .02). Patients with a low LCR had significantly worse DFS (Log Rank = 34.98, P < .01) and OS (Log Rank = 43.17, P < .01) than those with a high LCR. The LCR was an independent prognostic factor for both DFS (hazard ratio (HR) = 0.35, 95% confidence interval (CI): 0.20-0.62, P < .01) and OS (HR = 0.18, 95% CI: 0.08-0.37, P < .01).Conclusions:The LCR is a superior predictor of survival in stage I to III CRC, and patients with a low LCR have an inferior outcome; however, additional studies are required to validate its prognostic role.

Prognostic and Therapeutic Significance of Circulating Tumor Cell Phenotype Detection Based on Epithelial-Mesenchymal Transition Markers in Early and Midstage Colorectal Cancer First-Line Chemotherapy.

Purpose Epithelial-mesenchymal transition (EMT) is related to the process of metastasis and challenges the detection of circulating tumor cells (CTCs) based on epithelial cell adhesion molecules. Circulating tumor cells (CTCs) have been proven to be a prognostic indicator of colorectal cancer (CRC). Although there is evidence that CTC heterogeneity based on EMT markers is associated with disease progression, no standard recommendations have been established for clinical practice. This study is aimed at evaluating the prognostic significance of dynamic CTC detection based on EMT for early and midstage colorectal cancer patients. Methods 101 patients with early to midterm CRC were admitted from January 2016 to September 2018. All patients underwent CRC radical surgery and standard chemotherapy. Patients in the postchemotherapy were able to epithelial mesenchymal transformed (EMT) CTC testing in peripheral blood using the CanPatrol™ system. Multiple CTC tests were performed according to patient's own condition and different follow-up time points. Based on patient's basic information and follow-up data, the Kaplan-Meier method was utilized to establish the progression-free survival model, and the log-rank test was utilized to compare the survival rates between the two groups. Result Total CTC change of the patient is the best method to predict whether progression-free survival progresses in tumor patients (Area = 0.857). The second detection of total number of CTCs (P < 0.01) detected after chemotherapy, epithelial CTCs (P = 0.032), the increased total number of CTCs (P < 0.01), and the increased number of mesenchymal CTCs (P = 0.015) are significantly related with patient's poor progression-free survival. Conclusion Analysis of the second CTC count and classification after follow-up are more related to the survival prognosis of the tumor. The joint analysis of CTC dynamic monitoring data is a good tool to judge patient's survival prognosis.