Search Results (401)

Background: Colorectal cancer (CRC) frequently metastasizes to the liver (CRLM), where M2-polarized macrophages shape an immunosuppressive pre-metastatic niche. The molecular cues driving this polarization remain unclear. Methods and Results: Using integrated transcriptomics, patient cohorts, and mouse models, we investigated the role of tissue inhibitor of metalloproteinases-1 (TIMP1) in CRLM. TIMP1 was consistently overexpressed in CRC tissues and associated with poor overall survival. CRC cells secreted TIMP1 into the tumor microenvironment, where it induced M2-like macrophage polarization and increased the expression of immunosuppressive mediators such as CSF1 and IRF4. In vivo, TIMP1 overexpression enhanced, whereas its knockdown reduced, liver metastatic burden. Immune profiling and depletion experiments indicated that these pro-metastatic effects were largely macrophage-dependent. Mechanistically, TIMP1 engaged CD63/β1-integrin on macrophages, activating AKT/mTOR signaling and stabilizing the M2 phenotype. Conclusions: CRC-derived TIMP1 remodels liver macrophages via the CD63/β1-integrin–AKT/mTOR pathway to promote a hepatic pre-metastatic niche. Pharmacologic inhibition of this signaling axis with the integrin antagonist cilengitide suppressed macrophage M2 markers and liver colonization in mice, supporting TIMP1–integrin signaling as a potential therapeutic target. Full article

Transarterial radioembolization (TARE) is an established therapy for primary and secondary hepatic malignancies. Outcomes depend heavily on dosimetry, which has evolved from empirical and body-surface-area methods to partition and voxel-based approaches. This review summarizes current evidence for advanced (personalized) dosimetry across tumor types, highlights emerging dose–response concepts, and outlines practical barriers and implementation strategies. A narrative review of peer-reviewed clinical studies and trials evaluating dosimetry in TARE, with emphasis on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), metastatic colorectal cancer (mCRC), neuroendocrine tumor (NET), and breast cancer liver metastases, was performed with comparison of single-compartment medical internal radiation dosimetry method (MIRD), partition (multicompartment) methods, and voxel-based dosimetry methodologies. Personalized dosimetry improves outcomes in multiple tumor types. A randomized trial in HCC showed superior overall survival with partition-based dosing versus MIRD. In selective HCC treatments, voxel-derived metrics (e.g., D95) correlate with complete pathologic necrosis, suggesting benefit beyond mean dose targets. For iCCA, data associate higher tumor doses with better radiologic response, progression-free survival, and downstaging. In mCRC, voxel-based and threshold analyses link specific tumor and margin doses with metabolic/radiographic response and survival. Smaller series in NET and breast cancer indicate dose–response relationships using advanced dosimetry. Evidence supports broader adoption of advanced dosimetry in TARE. Emerging strategies that ensure adequate coverage of the “coldest” tumor regions and thoughtful particle-load planning may further optimize results. Standardized protocols, prospective validation, and scalable workflows are needed to accelerate implementation. Full article

Background/Objectives: Fibrillarin (FBL) is a key nucleolar methyltransferase involved in ribosome biogenesis through 2′-O-ribose methylation of rRNA. While its oncogenic role has been reported in several cancer types, its expression and function in human colorectal cancer (CRC) have remained largely unexplored. This study aims to investigate the expression of FBL in human CRC tissues and cell lines and to determine its functional role in tumor progression and metastasis. Methods: We examined FBL expression in paired human CRC primary tumors and liver metastases using immunohistochemistry. Functional studies were performed using SW-480 (primary tumor) and SW-620 (lymph node metastasis) CRC cell lines derived from the same patient. Cell migration, invasion, and 3D spheroid growth were analyzed following FBL downregulation. In vivo tumor growth was assessed in SCID mice xenografted with FBL-deficient cells. Molecular changes were explored through phosphorylation arrays and Western blotting. Results: FBL expression was significantly higher in human metastatic lesions than in primary tumors. FBL downregulation impaired migration, invasion, and spheroid growth in SW-480 and SW-620 cells and reduced tumor growth in vivo. Mechanistically, FBL inhibition decreased activation of MAPK/ERK, PI3K/AKT, and JNK/p38 pathways and reduced phosphorylation of the transcription factor CREB. Conclusions: Our study identifies FBL as a potential contributor to colorectal cancer progression, with elevated expression associated particularly with metastatic disease. By demonstrating that FBL expression is elevated in patient-derived metastatic tissues and functionally promotes migration, invasion, and tumor growth, our findings expand the role of ribosome biogenesis factors beyond protein synthesis. The observed suppression of key oncogenic pathways and CREB phosphorylation upon FBL inhibition suggests that FBL integrates ribosomal regulation with cancer cell signaling. These insights open new avenues for targeting nucleolar activity in advanced CRC and highlight FBL as a potential biomarker and therapeutic target in metastatic disease. Full article

Background: Surgical resection (SR) and liver transplantation (LT) are the main curative options for non-hepatocellular carcinoma (non-HCC) liver malignancies, including colorectal liver metastases (CRLMs), intrahepatic cholangiocarcinoma (iCCA), hilar cholangiocarcinoma (hCCA), and neuroendocrine tumor liver metastases (NETLMs). Resection aims for negative margins and adequate hepatic reserve, while LT offers treatment for unresectable disease but is limited by donor scarcity, immunosuppression, and ethical constraints. Methods: A targeted literature search (2005–2025) was conducted using PubMed and Google Scholar with predefined MeSH terms combining “liver resection,” “hepatectomy,” and “liver transplantation” across non-HCC malignancies. Relevant studies, reviews, and guidelines were included. Results: For CRLMs, SR remains standard with 5-year overall survival (OS) up to 58%, while LT offers 60–83% in highly selected unresectable cases. In iCCA, resection achieves median survival around 40 months, and LT yields OS up to 69% in very early or neoadjuvant-controlled disease. For hCCA, the Mayo protocol combining neoadjuvant therapy with LT provides 5-year OS of 65–80%. In NETLMs, LT achieves 63–97% OS under strict criteria. Conclusions: SR remains first-line for resectable non-HCC malignancies, while LT provides superior outcomes in unresectable yet biologically favorable disease, emphasizing careful selection and organ allocation. Full article

Background/Objectives: Over the past few years, high-dose radioembolization (≥150 Gy) has become widely adopted for the treatment of primary liver cancer, while evidence for its application in hepatic metastases is still limited. The aim of this study was to evaluate the safety and efficacy of high-dose transarterial radioembolization (TARE) in patients with hepatic metastases using resin Yttrium-90 (⁹⁰Y) microspheres. Methods: In this retrospective analysis, patients who were treated with high-dose TARE for hepatic metastases with ⁹⁰Y resin microspheres between May 2019 and April 2025 were included. The primary outcomes were treatment efficacy and toxicity assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Treatment efficacy was evaluated based on radiological response according to Response Evaluation Criteria in Solid Tumors version 1.1, time to progression and overall survival (OS). Secondary outcomes included ⁹⁰Y PET/CT post-treatment voxel-based local deposition model dosimetry and its relations to response. Results: A total of 15 patients were included, with hepatic metastases originating from colorectal cancer (n = 11, 73.3%), neuroendocrine tumor (n = 3, 20%) and breast cancer (n = 1, 6.7%). Seven patients (47.7%) had undergone one or multiple prior loco(regional) liver treatments and 13 (86.7%) patients had prior systemic therapy. The median mean tumor absorbed dose was 160.7 Gy (IQR 127.6–245.0 Gy), and the median normal liver parenchyma dose was 40.3 Gy (IQR 21.7–52.3 Gy). Disease control was achieved in all patients, with partial response in 10 patients (66.7%) and stable disease in 5 patients (33.3%) after 3 months. The median OS was 26.5 months (95% CI 24.5 months to no estimate). Two patients (13.3%) experienced grade 3 laboratory toxicity. No grade 4 or 5 toxicities were observed. Conclusions: High-dose TARE with ⁹⁰Y resin microspheres resulted in a high disease control rate and demonstrated a favorable safety profile, even in this heavily pretreated cohort. Full article

Background: Radiomic feature robustness is a key prerequisite for the reproducibility and clinical translation of imaging biomarkers. Variability across software platforms can significantly affect feature consistency, compromising predictive modeling reliability. This study aimed to develop and validate a hierarchical clustering-based workflow for evaluating radiomic feature robustness within and across software platforms, identifying stable and reproducible features suitable for clinical applications. Methods: A multi-cancer CT dataset including 97 lesions from 71 patients, comprising primary colorectal cancer (CRC), colorectal liver metastases, and hepatocellular carcinoma (HCC), was analyzed. Radiomic features were extracted using two IBSI-compliant platforms (MM Radiomics of syngo.via Frontier and 3D Slicer with PyRadiomics). Intra-software reliability was assessed through the intraclass correlation coefficient ICC(A,1), while cross-software stability was evaluated using hierarchical clustering validated by the Adjusted Rand Index (ARI). A Composite Index (CI) integrating correlation, distributional similarity, and mean fractional ratio quantified inter-platform feature robustness. Results: Over 95% of radiomic features demonstrated good-to-excellent intra-software reliability. Several clustering configurations achieved ARI = 1.0, confirming strong cross-platform concordance. The most robust and recurrent features were predominantly wavelet-derived descriptors and first-order statistics, particularly cluster shade (GLCM-based) and mean intensity-related features. Conclusions: The proposed multi-stage framework effectively identifies stable, non-redundant, and transferable radiomic features across IBSI-compliant software platforms. These findings provide a methodological foundation for cross-platform harmonization and enhance the reproducibility of radiomic biomarkers in oncologic imaging. Full article

Background: Radiomics enables the extraction of quantitative imaging biomarkers that can non-invasively capture tumor biology and treatment response. Delta-radiomics, by assessing temporal changes in radiomic features, may improve reproducibility and reveal early therapy-induced alterations. This study investigated whether delta-texture features from contrast-enhanced CT could predict progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) liver metastases treated with cetuximab rechallenge plus avelumab within the CAVE trial. Methods: This retrospective substudy included 42 patients enrolled in the multicenter CAVE phase II trial with evaluable liver metastases on baseline and first restaging CT. Liver lesions were manually segmented by two readers, and radiomic features were extracted according to IBSI guidelines. Delta-values were calculated as relative changes between baseline and post-treatment scans. Reproducibility (ICC > 0.70), univariate and multivariable analyses, ROC/AUC, bootstrap resampling, cross-validation, and decision curve analysis were performed to evaluate predictive performance and clinical utility. Results: Among reproducible features, delta-GLCM Homogeneity emerged as the most robust predictor. A decrease in homogeneity independently correlated with longer PFS (HR = 0.32, p = 0.003) and OS (HR = 0.41, p = 0.021). The combined clinical–radiomic model achieved good discrimination (AUC 0.94 training, 0.74 validation) and stable performance on internal validation (bootstrap C-index 0.77). Decision curve analysis indicated greater net clinical benefit compared with clinical variables alone. Conclusions: This exploratory study provides preliminary evidence that delta-GLCM Homogeneity may serve as a reproducible imaging biomarker of response and survival in mCRC patients receiving cetuximab plus avelumab rechallenge. If validated in larger, independent cohorts, delta-radiomics could enable early identification of non-responders and support personalized treatment adaptation in immuno-targeted therapy. Given the small sample size, the potential for overfitting should be considered. Future work should prioritize prospective multicenter validation with a pre-registered, locked model and explore multimodal integration (radiogenomics, circulating biomarkers, and AI-driven fusion of imaging with clinical/omic data) to strengthen translational impact. Beyond imaging advances, these findings align with broader trends in personalized oncology, including response-adaptive strategies, multimodal biomarker integration, and AI-enabled decision support. Full article

Background: The molecular and clinical underpinnings of worse overall survival outcomes with liver metastasis of CRC are not well-defined. We therefore aimed to investigate molecular and clinical characteristics of liver metastasis of CRC in this comparative study. Methods: Patients diagnosed with metastatic CRC from 2014 to 2022 were identified using the institutional molecular database of CRC. Demographic, clinical, and molecular data were collected and analyzed using Fisher’s exact tests for categorical variables, Kaplan–Meier analysis, and multivariate Cox regression analysis. Results: We identified 299 total patients with metastatic CRC, including patients with liver metastasis (n = 205) and non-liver metastasis (n = 94). We observed a significantly higher incidence of liver metastasis among patients with colon cancer compared to rectal cancer (74% vs. 48%, p = 0.00013). There was no significant difference in the incidence of common driver mutations, including KRAS, BRAF, and TP53, in the liver versus non-liver metastasis cohorts. There was a trend toward worse median overall survival among patients with liver metastasis, though this was not statistically significant (42.2 vs. 47.6 months, p = 0.27). Liver metastasis was identified as a significant predictor of shorter time on frontline therapy (HR 1.82, p < 0.001), a surrogate for treatment response, with a median time of 13 months from first- to second-line treatment compared to 19.7 months in the non-liver metastasis cohort (p = 0.00098). KRAS mutations were a significant predictor of worse survival in the liver metastasis cohort only (HR 2.01, p < 0.001), while BRAF mutations were a significant predictor in the non-liver metastasis cohort (HR 3.42, p = 0.006). Conclusions: Liver metastasis of CRC is associated with shorter time on frontline therapy, indicative of potential chemotherapy resistance. Given similar incidence of molecular alterations in patients with liver metastasis and non-liver metastasis, therapeutic resistance may instead be related to the tumor microenvironment of the liver. Most notably, this is the first study to reveal that despite a similar incidence of molecular alterations, driver alterations including BRAF and KRAS mutations may have a distinct impact on survival outcomes depending on the site of metastasis. Full article

The traditional management of resectable colorectal liver metastases (CLMs) includes systemic therapy and curative (R0) surgery. Hepatocellular carcinoma (HCC) treatment options include R0 surgery, liver transplantation (LT), chemoembolisation, and targeted chemotherapy. Ablative techniques (radiofrequency ablation and microwave ablation) targeting liver lesions were until recently considered suitable only for patients deemed unfit for surgical resection. However, over time, data suggesting the non-inferior results of radical (A0) ablation compared with radical surgery have started to emerge. Given the lower complication rate of ablative therapies compared with surgery, the question arises as to whether ablation has the potential to replace the role of surgery in the treatment of HCC and colorectal cancer metastases to the liver. In this review, we address the current evidence on the topic and its possible impact on future clinical practice. Full article

Introduction: The aim of the study was to analyse the results and potential complications of local treatment with HDR (high dose-rate) brachytherapy of liver metastases from colorectal cancer, depending on the targeted therapy used and considering RAS gene mutation and chemotherapy in individual treatment lines. Material and methods: The study included 142 patients with oligoprogressive liver metastases who underwent HDR brachytherapy without changing the line of treatment, based on a retrospective analysis of 270 patients treated between 2015 and 2022. The impact of RAS gene mutations, lines of chemotherapy depending on the treatment regimens used, PFS (progression free survival), OS (overall survival), LC (local control) and the degree of radiological response were analysed. The impact of these drugs on hepatotoxicity and the risk of haemorrhagic complications was also analysed. Results: The presence of mutations in KRAS/NRAS genes (exons 2, 3, 4) had a statistically significant impact on PFS in the first, third and fourth lines of treatment, and on OS and LC in the third and fourth lines of treatment. In the third and fourth lines of treatment, patients with a mutation in the RAS gene had a poorer radiological response to treatment regardless of the chemotherapy used. PFS, OS and LC differed depending on the line of treatment and amounted to 17.5, 11, 8.5, 6 and 4 months, 27, 19, 13, 11 and 11 months, and 27, 19, 11, 6 and 6 months, respectively. The greatest benefit in terms of PFS was achieved by patients treated with first-line chemotherapy combined with epidermal growth factor receptor (EGFR) inhibitors, in the absence of RAS gene mutations. In the third line, the greatest benefit was achieved by patients treated with trifluridine/tipiracil in the absence of RAS gene mutations. The greatest percentage reduction in the volume of treated lesions and the highest percentage of control were observed in the first three lines of treatment. The toxicity of the treatment was low; only in the third and fourth lines of treatment were differences in the decrease in albumin levels found depending on the type of treatment used. Conclusions: A mutation in the RAS genes worsens the prognosis, regardless of the line of treatment and the systemic treatment used. The greatest benefit from brachytherapy is seen in patients in the first three lines of treatment without RAS mutations, treated with anti-EGFR chemotherapy in the first line and trifluridine/tipiracil in the third line. Combining brachytherapy of liver metastases with systemic treatment is safe, regardless of the systemic treatment used. Full article

Background/Objectives: This secondary analysis aims to evaluate various prognostic factors for overall survival (OS) and hepatic progression-free survival (hPFS) and to perform subgroup analyses regarding OS of patients with unresectable and chemotherapy-refractory liver metastases from colorectal cancer (LMCRC) treated by the combination therapy of transarterial chemoembolization (TACE) and microwave ablation (MWA) or with MWA alone. Methods: A total of 251 patients with unresectable and chemotherapy-refractory LMCRC were included retrospectively. Group A consisted of 184 patients who received a combination of TACE and MWA. A total of 67 patients were included in group B, who received only MWA. Group C summarizes the total number of 251 patients treated. For all groups, the influence of age, sex, number of metastases, the diameter and volume of the largest metastasis, and the occurrence of recurrence on OS and hPFS was determined using univariate cox regression analysis. OS was compared between patients with more than three metastases and those with three or fewer, as well as between patients with a diameter of largest metastasis of 3 cm or less with patients with a diameter of largest metastasis of more than 3 cm. The analysis of OS was carried out using the Kaplan–Meier method. Results: For all three groups, the parameters of age, sex, number of metastases, diameter and volume of the largest metastasis, complete ablation status, and recurrence were not significant prognostic factors for OS. The number of metastases had a statistically significant influence on hPFS in group C (p = 0.034) and trended towards significance in group A (p = 0.057). The mean OS of patients with three metastases or less was in all groups longer than patients with more than three metastases, however, with no statistically significant differences (p = 0.83, 0.451 and 0.84 for groups A, B and C, respectively). There were no significant differences regarding OS between patients with diameter of largest metastasis of 3 cm or less compared to patients with diameter of largest metastasis more than 3 cm in all groups (p = 0.316, 0.812 and 0.45 for groups A, B and C, respectively). Conclusions: We could not observe significant prognostic factors in the treatment of LMCRC on OS. Accordingly, patients with three metastases or less had non-significant longer OS than patients with more than three metastases. The number of metastases had a significant impact on hPFS of the whole patient cohort and borderline significant impact on hPFS in patients treated with TACE combined with MWA. Full article

Background: Robotic liver surgery is emerging as a key advancement in minimally invasive techniques, though it still faces several challenges. Meanwhile, colorectal cancer (CRC) continues to be a leading cause of cancer deaths, with liver metastases affecting 25–30% of patients. These metastases significantly burden healthcare systems by raising costs and resource demands. Methods: A narrative literature review was performed, resulting in the inclusion of 14 studies in our analysis. Fourteen studies met the inclusion criteria and were analyzed with attention to patient characteristics, surgical details, perioperative outcomes, and reporting limitations. For consistency, simultaneous robotic-assisted resection (RAR) refers to cases in which the colorectal primary and liver metastasectomy were performed during the same operative session. Results: The 14 studies included a total of 771 patients (520 males and 251 females), aged between 31 and 88, undergoing simultaneous robotic-assisted resection (RAR). Most were affected by rectal cancer (76%) and unilobar liver metastases (82%). All surgeries using the DaVinci system are represented by 62% wedge resection and 38% anatomical (21.39% major and 16.61% minor). Patients’ BMI ranged from 19.5 to 40.4 kg/m², the average blood loss was 181.5 mL (30–780), the median hospital stay was 7 days (range 2–28), and the mean operative time ranged from 30 to 682 min. Data on POLF (postoperative liver failure) are reported in two studies: Rocca et al., 1/90 patients; Marino et al., 1/40 patients. Biliary leak is reported in one case by Marino et al., while Winckelmans et al. reported a 2.6% incidence of biliary leak in the laparoscopic group and 3.4% in the robotic group. Conclusions: As research advances and new therapies emerge for colorectal liver metastasis (CRLM), surgery remains the mainstay of treatment. However, evidence is limited by small sample sizes, heterogeneous study designs, inconsistent reporting of perioperative chemotherapy, timing of surgery, metastasis localization, and complications. Robotic liver surgery has become a well-established technique and possibly represents the future for managing colorectal liver metastases. Further prospective and comparative studies with standardized outcome reporting are needed to define optimal patient selection and long-term effectiveness. Full article

Colorectal liver metastases (CRLM) management remains a complex conundrum in the context of potential curable disease. The combination of systemic therapy and surgery, with overall survival outcomes up to 58% at five years, has become the gold standard. Locoregional therapies have gained evidence in complementing surgery or even substituting it in selected cases. Adequate patient selection is paramount, but prognostic models have certain limitations that prevent their full implementation in clinical practice. A plethora of prognostic factors exists, with variable evidence supporting their definitive role. Thus, CRLM management decisions frequently vary depending on multidisciplinary team experience and hospital access to systemic and locoregional treatments. Definition of resectability has evolved in recent years due to technical developments in surgical and non-surgical approaches. Complexity is added when trying to fully understand the integration between local and systemic treatment. Whereas evidence in the context of resectable disease has been attempted in several phase III trials, definitive conclusions regarding the best approach to potentially resectable disease cannot be drawn. In addition, liver transplantation has gained evidence and is proposed in selected patients, raising a challenge regarding its integration and wider implementation. In this review, current standards in the management of CRLM regarding patient selection, resectability, surgical and non-surgical locoregional strategies, as well as the best systemic approach are covered. Full article

Background: Liver cancer, either primary or metastatic, is a leading cause of cancer-related deaths and in many cases is presented in stages requiring major hepatectomy. Adequate future liver remnant (FLR) volume is essential before any major hepatectomy. Portal vein embolization (PVE) has long been the standard technique for preoperative liver hypertrophy, but liver venous deprivation (LVD) has emerged as a novel method, potentially offering faster and superior results. The aim of this study is to compare FLR hypertrophy outcomes between LVD and PVE in patients undergoing major hepatectomy for liver malignancy. Methods: A systematic literature search was conducted across PubMed, Cochrane library, and clinicaltrials.gov for studies assessing FLR volume changes after LVD or PVE in patients with primary or secondary liver tumors undergoing liver resection. Data extraction was performed independently by two reviewers. The study protocol was registered in PROSPERO and was prepared according to the PRISMA guidelines. Results: Twelve retrospective cohort studies were included in this systematic review. Liver venous deprivation consistently demonstrated superior FLR hypertrophy, with a faster and higher percentage increase compared to PVE. Time to resection was also shorter in the LVD groups in most studies. Safety outcomes were comparable, with no consistent difference in post-procedural complications or mortality. Conclusions: Liver venous deprivation may potentially be a safe and effective alternative to PVE, offering more robust and rapid FLR hypertrophy with similar morbidity and mortality rates. While current evidence supports its superiority in selected patients, future validation with larger prospective clinical trials is essential before it can be adopted as standard management of patients with insufficient FLR volume. Full article

Background: Colorectal cancer is the third most diagnosed cancer and a leading cause of cancer-related deaths worldwide. Early detection significantly improves patient outcomes, yet many cases are identified only at late stages. The high molecular and genetic heterogeneity of colorectal cancer presents major challenges in accurate diagnosis, prognosis, and therapeutic stratification. Recent advances in gene expression profiling offer new opportunities to discover genes that play a role in colorectal cancer carcinogenesis and may contribute to early diagnosis, prognosis prediction, and the identification of novel therapeutic targets. Methods: This study involved 142 samples: 84 primary tumor samples, 27 liver metastases, and 31 adjacent non-tumor tissues serving as controls. RNA sequencing was performed on a subset of tissues (12 liver metastases and 3 adjacent non-tumor tissues) using a targeted RNA panel covering 395 cancer-related genes. Data processing and differential gene expression analysis were carried out using the DRAGEN RNA and DRAGEN Differential Expression tools. The expression of six genes involved in hypoxia and epithelial-to-mesenchymal transition (EMT) pathways (SLC16A3, ANXA2, P4HA1, SPP1, KRT19, and LGALS3) identified as significantly differentially expressed was validated across the whole cohort via quantitative real-time PCR. The relative expression levels were determined using the ΔΔct method and log2FC, and compared between different groups based on the sample type; clinical parameters; and mutational status of the genes KRAS, PIK3CA, APC, SMAD4, and TP53. Results: Our results suggest that the expression of all the validated genes is significantly altered in metastases compared to non-tumor control samples (p < 0.05). The most pronounced change occurred for the genes P4HA1 and SPP1, whose expression was significantly increased in metastases compared to non-tumor and primary tumor samples, as well as between clinical stages of CRC (p < 0.001). Furthermore, all genes, except for LGALS3, exhibited significantly altered expression between non-tumor samples and samples in stage I of the disease, suggesting that they play a role in the early stages of carcinogenesis (p < 0.05). Additionally, the results suggest the mutational status of the KRAS gene did not significantly affect the expression of any of the validated genes, indicating that these genes are not involved in the carcinogenesis of KRAS-mutated CRC. Conclusions: Based on our results, the genes P4HA1 and SPP1 appear to play a role in the progression and metastasis of colorectal cancer and are candidate genes for further investigation as potential biomarkers in CRC. Full article