Search Results (293)

Background: Colorectal cancer liver metastasis (CRLM) remains a major cause of mortality in colorectal cancer (CRC), while the upstream molecular mechanisms linking tumor cell adaptation and immune microenvironment remodeling remain poorly understood. Methods: By integrating single-cell RNA sequencing, multi-omics analysis, clinical cohorts, and functional experiments, we investigated the role and mechanism of TCF4 post-translational modification in CRLM progression. Results: We identified O-GlcNAcylated TCF4 as a critical driver of CRLM. TCF4 was significantly upregulated in CRLM and associated with poor prognosis. Mechanistically, OGT-mediated O-GlcNAcylation at Ser163 promoted TCF4 nuclear localization and enhanced its transcriptional activity. O-GlcNAcylated TCF4 directly activated GPX4 transcription, conferring ferroptosis resistance and preserving the malignant characteristics of CRC cells. Furthermore, TCF4 promoted CSF1 secretion, activating the CSF1/CSF1R axis to facilitate TAM recruitment and M2 macrophage polarization, thereby establishing an immunosuppressive metastatic niche. Conclusions: Our study reveals an O-GlcNAcylated TCF4–ferroptosis–immune regulatory axis that coordinates tumor intrinsic adaptation and microenvironmental remodeling during CRLM progression, providing potential therapeutic targets for preventing CRLM. Full article

Background: Early-onset colorectal cancer represents a growing global health challenge. Although differences between young and elderly patients are recognized, direct comparison of extreme age groups may further characterize their distinct clinical and therapeutic profiles. Methods: This is a retrospective, single-centre, observational study, comparing young patients (Group A: ≤50 years, n = 153) with elderly patients (Group B: ≥75 years, n = 533) during the period 1990–2025. Results: Group A presented higher rates of stage IV presentation (66.9% vs. 47.1%, p < 0.001), T4 tumors, N2 nodal involvement, distal tumor localization and synchronous metastasis (87.5% vs. 70.6%, p = 0.001), predominantly involving the liver and peritoneum. Younger patients received more intensive adjuvant and metastatic systemic treatment. The mOS was 52.8 months for Group A compared to 26.4 months for Group B (HR 2.29, 95% CI 1.57–3.54, p < 0.001) and DFS was longer in Group A (28.6 vs. 19.1 months; HR 2.26, 95% CI 1.55–3.29, p < 0.001). No statistically significant differences were observed in first- or second-line PFS between the cohorts. Conclusions: Early-onset colorectal cancer exhibits a more adverse clinicopathological profile. Younger patients showed longer overall and disease-free survival in this cohort, although these findings should be interpreted with caution given potential differences in treatment exposure, baseline fitness, comorbidity burden and the substantial temporal heterogeneity of the study period. Full article

Background: Colorectal cancer liver metastases (CRCLMs) are associated with treatment resistance, and poor survival. We aimed to measure the differences in the immune composition of primary colorectal tumors and CRCLMs to identify prognostic and potentially actionable differences in the tumor microenvironment (TME). Methods: We created two independent cohorts of patients that had surgical resection of primary colorectal tumor and CRCLM resection at the Yale Cancer Center, comprising of 84 and 95 cases arranged in tissue microarray (TMA) format. Using multiplex quantitative immunofluorescence (QIF) we measured CD4⁺, CD8⁺, and FOXP3⁺ immune cells across spatially-resolved compartments within the tumor samples. We then assessed the association of clinicopathologic variables and treatment-specific outcomes with immune cell composition. Results: CRCLMs showed significantly higher CD8⁺ effector T-cells and significantly lower FOXP3⁺ regulatory T-cell infiltration than primary tumors. In addition, high CD8⁺ T-cell infiltration within the cancer cell compartment of CRCLMs was prominently associated with longer overall survival in both cohorts (Cohort1: HR = 0.38, p = 0.032; Cohort2: HR = 0.23, p = 0.046). Neoadjuvant chemotherapy (NAC) was associated with a significant increase in CD8⁺ T-cells across all tumor tissue regions in CRCLMs (p < 0.01 in both cohorts). However, NAC was not associated with improved three-year progression-free survival in either cohort (Cohort1: HR = 0.75, p = 0.43; Cohort2: HR = 0.97, p = 0.93). Conclusions: The TME of CRCLMs is characterized by reduced Tregs and increased TILs in NAC-treated patients. Furthermore, increased CD8⁺ infiltration in the tumoral compartment within CRCLMs is associated with improved survival. Our results describe local adaptive anti-tumor immune responses seen in CRCLM and underscore the need for novel therapeutic strategies that leverage TME alterations. Full article

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and liver metastasis remains a major contributor to poor prognosis and treatment failure. Increasing evidence indicates that the gut–liver axis plays a critical role in colorectal cancer liver metastasis (CRLM) by linking intestinal microbial alterations with hepatic microenvironmental remodeling. Gut dysbiosis and intestinal barrier disruption facilitate the translocation of microbial components and metabolites through the portal circulation, contributing to hepatic immune remodeling, extracellular matrix alteration, and the establishment of a pre-metastatic niche favorable for tumor colonization. During metastatic progression, specific tumor-associated microorganisms may further promote circulating tumor cell (CTC) survival, immune evasion, and metastatic adaptation, while intratumoral microbiome alterations and metabolic reprogramming may influence tumor growth and therapeutic responses. This review summarizes the current understanding of gut–liver axis-mediated regulation of CRLM, focusing on intestinal barrier dysfunction, microbial translocation, hepatic pre-metastatic niche formation, tumor cell–microbiota interactions, and emerging clinical applications. Unlike previous reviews that have primarily focused on gut microbiota alterations in colorectal carcinogenesis, this review emphasizes the contribution of gut-derived microbial signals to liver-specific metastatic evolution. In addition, we discuss current challenges, including limited human causal evidence, technical issues in low-biomass microbiome analysis, and the need for longitudinal clinical validation. Future integration of spatial multiomics, prospective cohorts, and personalized microbiome-based interventions may provide new opportunities for early risk prediction and precision management of CRLM. Full article

As of 2020, liver cancer has emerged as the fifth most common cancer and the third leading cause of cancer death worldwide, following lung and colorectal cancers. The most prevalent type is hepatocellular carcinoma (HCC), originating from hepatocytes. Despite advancements, liver cancer treatment outcomes remain poor due to metastasis and recurrence. Existing anticancer drugs often exhibit narrow therapeutic windows and limited selectivity for cancer cells. Manilkara zapota (L.) P. Royen has attracted significant scientific attention because of its diverse bioactive constituents and potential therapeutic properties. Of particular interest in this review, we explored the molecular connectivity of oxidative stress-induced liver cancer. We discussed the underlying mechanisms of Manilkara zapota (L.) P. Royen involved in cancer and inflammation. The phytochemical constituents were also highlighted in this study. The phytochemicals reported from Manilkara zapota (L.) P. Royen included flavonoids, tannins, saponins, and phenolic compounds. These compounds demonstrated potential anticancer activities through mechanisms such as induction of apoptosis, inhibition of cell proliferation, modulation of oxidative stress, and regulation of PI3K/Akt and NF-κB signaling pathways. Further investigations are required to clarify the benefit–risk profile of Manilkara zapota (L.) P. Royen through large-scale clinical trials. Collectively, the current evidence suggests that this plant may offer a promising strategy for cancer management, provided that such interventions are optimized to minimize adverse effects. Full article

Background: Colorectal cancer is the third most commonly diagnosed cancer in the world. Liver metastases are frequent, adversely affecting patient prognosis. We compared progression-free survival and overall survival in colorectal cancer patients with liver metastasis treated with surgical resection or stereotactic body radiotherapy. No previous study had shown superiority of one treatment option over the other. Methods: We conducted a retrospective cohort study of 40 colorectal cancer patients with liver metastasis treated with surgical resection or stereotactic body radiotherapy at the Hebrew University-Hadassah Medical Center. Patient demographics, tumor characteristics, treatment details, and survival outcomes were analyzed. Kaplan–Meier curves and log-rank tests were used for survival analysis. Results: The median overall survival for the entire cohort was 44 months (95% CI 29–59 months). In patients treated with surgical resection, the median overall survival was 51 months (95% CI: 36–67 months), while in patients treated with stereotactic body radiotherapy the median overall survival was 32 months (95% CI: 21–43 months), a non-statistically significant result (p = 0.306). The number of lobes involved did not significantly impact overall survival (p = 0.214). Additionally, it did not significantly affect progression-free survival (p = 0.41). Liver metastases located in the left lobe led to considerably worse progression-free survival compared to other regions involved, specifically in the patients who underwent surgery. Conclusions: Our findings underscore the importance of personalized treatment strategies tailored to the distinct characteristics of colorectal cancer patients with liver metastasis. Currently, surgical resection remains the standard of care. Further research is warranted to address the possibility of extending SBRT to first-line treatment in selected unresectable patients. Full article

Liver transplantation (LT) has evolved from a contraindicated procedure for malignancy into an established oncologic therapy for selected primary and secondary hepatic cancers. Advances in tumor biology, molecular profiling, immunotherapy, and peri-transplant management have expanded transplant indications beyond hepatocellular carcinoma (HCC) to include perihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, colorectal liver metastasis (CRLM), neuroendocrine liver metastasis (NELM), and rare hepatic malignancies. The 2024 TransMet randomized controlled trial, demonstrating a 5-year overall survival (OS) of 73% with LT plus chemotherapy versus 9% with chemotherapy alone for unresectable CRLM, established the first Level 1 evidence supporting transplantation as a curative oncologic intervention in metastatic disease. These advances necessitate a modern framework for clinical trial design and research prioritization in transplant oncology. This manuscript proposes a comprehensive framework for future transplant oncology trials addressing endpoint selection, biomarker-driven patient selection, trial methodology, immunosuppression optimization, surveillance strategies, and ethical organ allocation. OS and transplant benefit are emphasized as the preferred primary endpoints for CRLM and NELM, whereas recurrence-free survival is recognized as retaining distinct clinical and prognostic value in HCC, underscoring that endpoint selection should be disease-specific rather than universally standardized. Emerging biomarkers—including circulating tumor DNA, AFP dynamics, and molecular and functional imaging profiling—are stratified into established, prospectively validated, and investigational categories to clarify their current clinical applicability. Randomized controlled trials, adaptive platform and enrichment designs, biomarker-stratified randomization, registry-based trials, and prospective registries are presented as complementary strategies tailored to disease prevalence and feasibility, alongside explicit consideration of how graft source—particularly the predominance of living donor liver transplantation in Asia versus deceased donor systems elsewhere—shapes trial design and interpretation. The manuscript further examines tumor biology-based immunosuppression, immune checkpoint inhibitor integration, and management of post-transplant recurrence. A precision medicine vision is proposed in which transplant candidacy is determined by biologic behavior and molecular signatures rather than morphology alone, with proposed trial frameworks offering an actionable research agenda for the next decade of transplant oncology. Full article

Background: Right-sided metastatic colon cancer represents a clinically distinct subgroup with inferior outcomes and uncertain optimal biologic treatment selection, even among patients with RAS wild-type disease. Real-world data focusing specifically on right-sided RAS wild-type metastatic colon cancer remain limited. This study aimed to describe clinicopathologic characteristics, metastatic patterns, treatment approaches, and survival outcomes in this population using a national multicenter registry. Methods: This retrospective multicenter cohort study was conducted using data from the ONKO-KOLON Türkiye registry. Patients with pathologically confirmed KRAS/NRAS wild-type metastatic colorectal cancer and available primary tumor localization were evaluated. The main analytic cohort included patients with right-sided metastatic colon cancer, defined as right colon or transverse colon tumors. Left-sided colon cancer patients were used as a contextual comparator, while rectal cancer patients were excluded from sidedness-based colon comparisons. Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were evaluated using Cox regression analyses. Results: Among 1079 patients in the source cohort, primary tumor localization was available in 1065 patients. Of these, 213 had right-sided colon cancer, 464 had left-sided colon cancer, and 388 had rectal cancer. In the right-sided cohort, median age was 61.5 years, 64.3% were male, and 66.7% had synchronous/de novo metastatic disease. Liver metastasis was the most common metastatic site (63.4%), followed by lymph node (31.0%), lung (21.1%), and peritoneal metastases (15.5%). First-line anti-VEGF-based treatment was used in 46.0% of patients, while anti-EGFR-based treatment was used in 40.8%. Among evaluable patients, the objective response rate was 46.8% and the disease control rate was 79.2%. Median progression-free survival was 10.0 months, and median overall survival was 24.0 months. In unadjusted exploratory analysis, median OS was 27.0 months with anti-EGFR-based treatment and 17.0 months with anti-VEGF-based treatment (log-rank p = 0.022), whereas median PFS was 10.0 months in both groups. In an extended covariate-adjusted multiple-imputation sensitivity model, the anti-EGFR OS estimate did not meet statistical significance (adjusted HR 0.66, 95% CI 0.43–1.00; p = 0.051). In a secondary contextual comparison, median overall survival was shorter in the right-sided than in the left-sided colon cancer group (24.0 vs. 28.0 months; HR 1.47, 95% CI 1.19–1.82; p < 0.001), whereas progression-free survival did not differ significantly. Conclusions: This study provides a descriptive account of metastatic patterns, treatment approaches, and outcomes in a dedicated right-sided RAS wild-type metastatic colon cancer cohort. The unadjusted OS difference between biological treatment groups was not confirmed after measured covariate adjustment and should not be interpreted as evidence of comparative treatment effectiveness. Because molecular profiling was incomplete, this study cannot identify biomarker-defined treatment subgroups. Prospective studies with complete, predefined molecular characterization are needed before molecularly informed treatment selection hypotheses can be evaluated in this population. Full article

Background/Objectives: Liver metastasis develops in approximately 50% of patients with colorectal cancer. Invasion of the biliary tract from colorectal liver metastasis (CRLM) is rarely reported. Preoperative diagnosis remains elusive, prohibiting optimal surgical management. The objective of this systematic review was to summarize the clinical, radiological, pathological, and treatment characteristics of ibCRLM and describe the reported outcomes. Methods: A systematic literature search of the Medline, Embase, Web of Science, CENTRAL, and CINAHL databases was undertaken for studies reporting clinical outcomes of patients with ibCRLM, up to May 2026. An individual patient data analysis approach was utilized. Results: Thirty-eight case reports and 10 case-series, incorporating 228 patients with biliary involvement from CRLM, were identified. Mean age was 62.4 ± 10.9 years, with a male-to-female ratio of 3.2:1. The majority of metastatic lesions were metachronous in 71.1% and solitary in 59.1% of patients. Surgical treatment was implemented in 89.2% of patients. Major hepatectomy was the most common procedure, being performed in 46.2% of patients, followed by minor hepatectomy in 38.7% and pancreatoduodenectomy in 4.3%. After a median follow-up of 52.5 months (range 2–164 months), the survival rate was 60.5%. Non-survivors were found to have significantly more synchronous CRLM (50% versus 0, p = 0.008), while a single patient did not receive any curative-intent treatment and died 20 days following CRLM presentation. Conclusions: IbCRLM is a distinct clinicopathological presentation of CRLM with characteristic radiological and pathological features. The available evidence suggests that selected patients may achieve favorable long-term outcomes following complete surgical resection, although these findings should be interpreted with caution given the limitations of the available literature. Full article

Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide, and metabolic reprogramming is increasingly recognized as an important feature of its progression. Among these changes, fatty acid metabolism (FAM) has drawn growing attention because it supports energy supply, membrane synthesis, redox balance, and stress adaptation in tumor cells. CRC cells can increase fatty acid uptake, activate de novo synthesis, adjust fatty acid oxidation (FAO), and alter lipid droplet (LD) dynamics according to metabolic demand. These processes are strongly influenced by the hypoxic tumor microenvironment. Under hypoxic conditions, signaling pathways centered on hypoxia-inducible factors (HIFs) reshape lipid uptake, synthesis, oxidation, and storage, allowing CRC cells to maintain survival and adapt to limited oxygen and nutrient availability. Increasing evidence suggests that this metabolic shift is closely linked to invasion, metastasis, stem-like behavior, and resistance to therapy. In this review, we provide an integrated overview of the hypoxia–FAM axis in CRC. We first summarize the major steps of FAM reprogramming, then highlight how hypoxia reshapes these processes through HIF-dependent and related pathways. We also discuss FAM crosstalk with stromal and immune cells, experimental models, and metabolic heterogeneity between primary CRC and liver metastases. Finally, we discuss therapeutic strategies targeting FAM and hypoxia-associated signaling in CRC. Full article

Purpose: This study aimed to determine the optimal temporal threshold for distinguishing “early” from “late” liver metastasis in patients who developed liver metastasis after colorectal cancer (CRC) surgery, and to evaluate whether KRAS and BRAF^V600E mutations, along with other clinicopathological factors, are associated with the timing of liver metastasis. Methods: This retrospective study utilized clinical and pathological data from patients who developed liver metastasis after radical CRC surgery at two centers from 2019 to 2023. X-tile software was used to identify the optimal temporal threshold. Logistic regression analysis was applied to determine if KRAS/BRAF^V600E mutations and other potential factors are independently associated with the time to onset of liver metastasis. Results: X-tile analysis identified 11 months post-surgery as the optimal cutoff for distinguishing early metachronous liver metastasis (EMLM) from late metachronous liver metastasis (LMLM), classifying 114 cases into the EMLM group and 72 into the LMLM group. Comparative analysis indicated statistically significant differences between the two groups in lymphovascular tumor emboli, perineural invasion, and postoperative adjuvant therapy (p < 0.05). Logistic regression analysis revealed that neither KRAS mutation (OR, 1.185; 95% CI: 0.641–2.190; p = 0.587) nor BRAF^V600E mutation (OR, 2.836; 95% CI: 0.302–26.642; p = 0.363) was independently associated with the timing of liver metastasis. In contrast, postoperative adjuvant therapy showed a statistical association with a likelihood of LMLM (OR, 0.253; 95% CI: 0.105–0.611; p = 0.002). Conclusions: This study identified 11 months post-CRC surgery as the optimal cutoff for differentiating EMLM versus LMLM. In this cohort, no statistically significant association was observed between KRAS/BRAF^V600E mutations and the timing of liver metastasis, whereas postoperative adjuvant therapy was statistically correlated with the likelihood of LMLM. This stratification may guide personalized surveillance strategies and provide valuable insights for future mechanistic investigations into the temporal heterogeneity of post-surgical liver metastasis. However, the interpretation and generalization of the findings require external validation in prospective cohorts. Full article

Despite advances in systemic therapies, metastatic colorectal cancer (mCRC) remains largely incurable, underscoring persistent gaps in our understanding of metastatic progression and therapeutic resistance. Emerging evidence suggests that gut and tumor-associated microbial communities may contribute to metastatic progression by shaping organ-specific niches, disrupting intestinal and vascular barriers, remodeling immune and stromal microenvironments, and altering host–microbial metabolism. This review synthesizes current evidence on the involvement of gut and intratumoral microbial communities in colorectal cancer metastasis, with emphasis on liver, lung, lymphatic, and peritoneal metastatic patterns; microbial translocation and barrier dysfunction; microbiome–tumor microenvironment interactions; and metabolic pathways such as bile acid, short-chain fatty acid, and tryptophan metabolism. Furthermore, distinct microbial signatures have been associated with responses to chemotherapy, radiotherapy, immunotherapy, and targeted therapies, supporting their potential value as candidate biomarkers for treatment stratification and prognosis, particularly when interpreted alongside treatment exposure and longitudinal microbiome dynamics. Finally, we discuss microbiome-targeted interventions as emerging adjunctive strategies that may help modulate treatment response, while emphasizing the need for standardized, longitudinal, and mechanistically validated studies before clinical translation in mCRC. Full article

Background/Objectives: Sacituzumab govitecan (SG, IMMU-132) is a TROP2-directed antibody–drug conjugate carrying SN-38. Patients with colorectal liver metastasis (CRLM) still have limited treatment options after first-line systemic therapy, and the preclinical pharmacological value of TROP2-directed SN-38 delivery in CRLM remains insufficiently defined. Methods: Public single-cell RNA-sequencing data were reanalyzed to explore the distribution of TACSTD2/TROP2-positive epithelial-associated cells in adjacent normal tissues, primary colorectal cancer, and CRLM. The prognostic relevance of TACSTD2 was evaluated using the Kaplan–Meier Plotter database. TROP2-knockdown and TROP2-overexpressing colorectal cancer models were used to assess IMMU-132 response in vitro and in vivo. Pharmacological antitumor activity was further evaluated using subcutaneous xenografts, syngeneic intrasplenic liver metastasis models, and CRLM patient-derived organoids (PDOs). Transcriptomic profiling and γ-H2AX immunofluorescence were used to explore treatment-associated molecular changes. Results: At the patient/sample level, TACSTD2/TROP2-positive epithelial-associated cells showed numerically higher proportions in primary colorectal tumors and liver metastases than in adjacent normal tissues, and high TACSTD2 expression was associated with inferior overall survival in a public survival database. TROP2 knockdown attenuated IMMU-132-induced growth inhibition, apoptosis, and suppression of colony formation. In vivo, IMMU-132 suppressed colorectal tumor growth and reduced liver metastatic burden, with more evident activity in human TROP2-overexpressing models. In a limited exploratory CRLM PDO cohort established after first-line therapy, liver metastasis-derived PDOs showed lower normalized AUC values than primary tumor-derived PDOs. Transcriptomic analysis and representative γ-H2AX immunofluorescence suggested that IMMU-132 treatment was associated with changes in adhesion/cytoskeletal-related pathways, Wnt/cancer-associated transcriptional programs, and DNA damage-associated signals. Conclusions: These in vitro, in vivo, and PDO-based findings support further preclinical pharmacological evaluation of TROP2-directed SN-38 delivery by IMMU-132 in biomarker-annotated CRLM models, particularly in the post-first-line systemic therapy setting. Full article

Background/Objectives: Extra virgin olive oil (EVOO), a key component of the Mediterranean diet, has attracted research interest because olive-derived phenolics demonstrate potential anticancer activity in experimental models. This review summarizes evidence concerning whole EVOO, phenolic-enriched EVOO, olive phenolic extracts, and the isolated compounds hydroxytyrosol, oleuropein, oleocanthal, and oleacein. Methods: A structured narrative search of PubMed, Web of Science, ScienceDirect, and Google Scholar was conducted for literature published between 2015 and 2025. Evidence was reviewed for breast, prostate, colorectal, pancreatic, bone, oral, liver, gastric, hematological, and brain cancers. Comparatively limited evidence concerning cervical, endometrial, ovarian, melanoma, non-melanoma skin, and thyroid cancers was summarized separately. Results: The molecular evidence was derived primarily from cell culture and animal studies using isolated phenolics and concentrated extracts. Preclinical studies indicate that EVOO phenolics may demonstrate anticancer activity through multiple mechanisms, including antioxidant activity, anti-inflammatory effects, cell cycle arrest, induction of apoptosis, inhibition of metastasis, anti-angiogenic activity, and modulation of key signaling pathways, such as PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Wnt/β-catenin, p53, and epithelial–mesenchymal transition-related pathways. Most molecular and pathway-level evidence was obtained using isolated phenolic compounds in cell culture or animal models, whereas evidence directly examining whole EVOO consumption was largely observational and substantially more limited. Experimental studies also reported that oleocanthal induced lysosomal membrane permeabilization, whereas hydroxytyrosol and oleuropein promoted mitochondria-mediated apoptosis. Furthermore, preclinical combination studies suggested enhanced tumor-cell sensitivity to selected chemotherapeutic, targeted, and immunotherapeutic agents. However, these effects have not been established in patients. Human evidence remains limited mainly to observational dietary associations and small exploratory interventions, with no conclusive demonstration of cancer prevention or therapeutic efficacy. Conclusions: Isolated EVOO-derived phenolic compounds demonstrated promising anticancer mechanisms in preclinical models. However, these results should not be directly extrapolated to dietary EVOO because experimentally administered doses, bioavailability, metabolism, and food-matrix interactions differ substantially from human dietary exposure. Therefore, well-designed studies using chemically characterized EVOO, pharmacokinetic investigations, and controlled human trials are required before dietary or clinical recommendations can be made. Full article

Background/Objectives: Colorectal liver metastases (CRLMs) are a major contributor to recurrence and mortality in colorectal cancer (CRC), with approximately a quarter of patients developing liver metastases over the course of the disease. Bone-marrow-derived myeloid lineages are sent into the circulatory system and colonize pre-metastatic niches, yet the transcriptional programs by which they establish a pro-metastatic microenvironment remain incompletely defined. Methods: Using an MC38 splenic-injection CRLM mouse model, we generated single-cell RNA sequencing (scRNA-seq) profiles of FACS-sorted CD11b⁺Gr1⁺ bone marrow myeloid cells, together with bulk RNA sequencing profiles of bone marrow and peripheral blood. Downstream analyses were performed in silico, including clustering and annotation, trajectory inference, cell–cell communication analysis, weighted gene co-expression network analysis (WGCNA), and pathway enrichment, with subset specificity examined against a public dataset of E. coli (Escherichia coli)-infected mice. Results: Within the CD11b⁺Gr1⁺ compartment, a CCR2⁺ neutrophil-like population (Ly6g⁺S100a8/9⁺) emerging during terminal differentiation was identified, which was enriched in CRLM mice but nearly absent in controls. Communication inference revealed an FN1-CD44 interaction involving mature neutrophils, which was associated with an epithelial–mesenchymal transition signature and upregulation of Tgfb1 and Il1b. This subpopulation was not recovered in the infection dataset, suggesting relative specificity to CRLMs. Conclusions: Within the constraints of a splenectomized hepatic colonization model, integrated transcriptomic analysis highlighted a CCR2⁺ bone marrow neutrophil-like population as a candidate contributor to CRLM, challenging the view that CCR2⁺ pro-metastatic myeloid cells are exclusively monocytic and suggesting candidate biomarkers and therapeutic targets for further study. Full article