SPP1 Drives Colorectal Cancer Liver Metastasis and Immunotherapy Resistance by Stimulating CXCL12 Production in Cancer-Associated Fibroblasts.

This study aimed to explore the role of plasma methylated SEPT9 (mSEPT9) in predicting liver metastasis (LM) in colorectal cancer (CRC) patients. The clinicopathological information of 115 consecutive CRC patients were collected. The differences of clinical characteristics and several biomarkers between CRC patients with LM and those with non-liver metastasis (NM) were analyzed. Multivariate logistic regression analysis was used to identify the risk factors for predicting LM in CRC patients. Receiver operating characteristic curve (ROC) analysis was applied to investigate the sensitivity and specificity of potential biomarkers in indicating the presence of LM in CRC. Compared with the CRC without LM, the levels of plasma mSEPT9 and carcinoembryonic antigen (CEA) were significantly increased in CRC with LM. Multivariate logistic regression analysis showed that plasma mSEPT9 was an independent risk factor for predicting LM in CRC. ROC curves showed that mSEPT9 and CEA could efficiently distinguish LM from NM in CRC. The area under the curve (AUC) of mSEPT9 was 0.850, which was slightly higher than that of CEA (0.842). The optimal cut-off value of mSEPT9 was 35.09 with a sensitivity of 81.82% and a specificity of 73.33%, both similar with that of CEA (sensitivity 87.27% and specificity 75.00%). In addition, the combination of mSEPT9 and CEA had a higher specificity than CEA alone (81.70% Vs 75.00%). Our findings suggest, for the first time, that plasma mSEPT9 might serve as a potential biomarker to predict LM in CRC, which deserves further in-depth study.

This study aimed to examine the expression pattern of tumoral and circulating miR-93-5p in patients with colorectal cancer (CRC) liver metastasis (CRLM) and to explore its predictive and prognostic potential. CRLM tissue, surrounding non-tumor liver tissue, and serum were obtained from 35 patients with CRLM. The expression pattern of tissue and circulating miR-93-5p in patients with CRLM was determined using quantitative polymerase chain reaction, using miR-16-5p for normalization. Sample-based cut-off values for CRLM and serum miR-93-5p expression were calculated using Receiver Operating Characteristic curve analysis to stratify the patients into high and low miR-93-5p expression groups which were that compared with patients' clinicopathological data, therapy response, one-year disease-free survival, and disease recurrence. Relative miR-93-5p expression was higher in CRLM in comparison to the non-metastatic liver tissue (p<0.001). CRLM miR-93-5p expression showed moderate negative correlation with carcinoembryonic antigen levels (r=-0.406; p=0.016). There were no differences in high-/low-miR-93-5p expression and therapy responders vs. non-responders, which was confirmed in vitro using metastatic and normal colonic cells SW620 and HCEC-1CT, respectively. No difference was observed in one-year recurrence-free survival in patients with high vs. low miR-93-5p expression in CRLM or serum. However, high miR-93-5p serum levels were significantly associated with early disease recurrence (p=0.035). In conclusion, miR-93-5p serum levels could be potentially used as a prognostic factor for early disease recurrence in CRLM patients.

Several long non-coding RNAs (lncRNAs) play important roles in the regulation of liver metastasis in colorectal cancer (CRC) patients. We previously described the potential involvement of HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS), miR-125a-5p, and peptidyl arginine deiminase 2 (PADI2) in promoting liver metastasis in CRC patients. In the present study, we verified the significant upregulation of HOXA11-AS and PADI2, as well as the downregulation of miR-125a-5p, in CRC patients with liver metastasis. Overexpression and knockdown studies of HOXA11-AS or PADI2, as well as gain-/loss-of-function studies of miR-125a-5p, revealed a positive correlation between HOXA11-AS and PADI2 and a negative correlation with miR-125a-5p in the regulation of liver metastasis in CRC cell lines. Overall, we conclude that HOXA11-AS promotes liver metastasis in CRC by functioning as a miR-125a-5p sponge and describe a novel HOXA11-AS–miR-125a-5p–PADI2 regulatory network involved in CRC liver metastasis.

e16080 Background: Liver metastasis (LIM) is the leading cause of death in colorectal cancer (CRC) patients. Early detection of LIM may improve outcome in CRC patients. The aim of this study was to evaluate the feasibility of predicting LIM of CRC using methylation profiles. Methods: We performed Roche targeted (~5.5 million methylation sites) bisulfite sequencing of matched primary, metastatic and their adjacent normal tissue samples from 5 CRC patients with LIM, 5 patients with lung metastasis (LUM) and 8 patients without metastasis in the training cohort (n = 48 samples). Differential methylation regions (DMR) of LUM were identified and a predictive model was developed. The model was further validated in primary tumor sample from nine patients (6 with LIM). Results: By comparing primary tumor vs adjacent normal tissues and metastatic tumor vs adjacent normal tissues in CRC patients with LIM, we identified 28954 common DMRs which indicating the methylation characteristic of CRC with LIM. Similarly, 16187 DMRs were identified in patients with LUM. 9179 DMRs are shared in both LIM and LUM comparisons which should be the common characteristic of CRC tumor tissue regardless of the location of metastasis. 7008 DMRs are LUM specific and 19775 DMRs are LIM specific. In order to predict LIM in primary, early changes in LIM specific DMRs should be identified. Hence, we further selected 4134 DMRs by chossing significantly differentically methylated regions between LIM primary tissues and LUM primary tissues. To increase the ability of distinguishing LIM from other normal tissues and non-matastasis CRC tumors, 1215 DMRs were finally selected which also showed increasing or decreasing trend of methylation level through the progression of CRC. The final 1215 biomarkers were used to construct a random forest model using methlylation profile of 5 CRC patients with LIM as positive training data and 5 CRC patients with LUM as well as 8 patients without metastasis as negative training data. Through the feature recursive elimination method, one methylation site (chr8.72468901-72469000) was identified with ROC of 0.9 in the training dataset. The predictive model was validated in an independent dataset which is composed of 6 patients with LIM and 3 patients without metastasis, and achieved an AUC of 0.87. Conclusions: Our findings demonstrate the utility of methylation biomarkers for the molecular characterization of metastatic precursors, with implications for prediction and early detection of liver metastasis in CRC.

The tumor-derived factors involved in the expansion and accumulation of myeloid-derived suppressor cells (MDSCs) in metastatic dissemination of colorectal cancer (CRC) to the liver has not been studied. Immunohistochemistry was used to detect sphingosine-1-phosphate receptor 1 (S1PR1) and signal transducer and activator of transcription-3 (STAT3) in human colorectal tumors. IL-6 and interferon-γ were detected by enzyme-linked immunosorbent assay (ELISA). Tumor growth, invasion, and migration were evaluated by MTT, transwell, and wound healing assays, respectively. Subcutaneous tumor-bearing and CRC liver metastasis (CRLM) nude mouse models were constructed. The percentage of MDSCs was measured using multicolor flow cytometry. Western blot assay was used to evaluate S1PR1 and p-STAT3 expression in MDSCs after separation from the liver and tumor by magnetic antibody. T-cell suppression assay was detected by carboxyfluorescein succinimidyl ester (CFSE). Aberrant co-expressed S1PR1 and p-STAT3 was correlated with metachronous liver metastasis and poor prognosis in CRC. A mutual activation loop between S1PR1 and STAT3 can enhance CRC cell proliferation, migration, and invasion in vitro and in vivo. The expression of p-STAT3 and its downstream proteins can be regulated by S1PR1. p-STAT3 was the dependent signaling pathway of S1PR1 in the promotion of cell growth and liver metastasis in CRC. The level of IL-6 and the associated MDSCs stimulated by the S1PR1–STAT3 correlated with the number of liver metastatic nodes in the CRLM mouse models and patients. Increased CD14+HLA-DR−/low MDSCs from CRLM patients inhibited autologous T-cell proliferation and predict poor prognosis. The S1PR1–STAT3–IL-6–MDSCs axis operates in both tumor cells and MDSCs involved in the promotion of growth and liver metastasis in CRC. MDSCs induced by S1PR1–STAT3 in CRC cells formed the premetastatic niche in the liver can promote organ-specific metastasis.

Introduction: Approximately half of all colorectal cancer (CRC) patients die as a consequence of metastases. Hemihepatectomy, occasionally in combination with radiofrequency ablation (RFA), is the only curative treatment available for patients with CRC liver metastases (CRCLM). Patient eligibility is based on established prognostic clinicopathological variables, however, 70% of patients still die within 5 years indicating that better prognostic markers are needed. Aurora kinase A (AURKA) is a driver of 20q gain-associated tumor progression and is associated with disease recurrence in stage III CRC patients. AIM: This study aimed to investigate the prognostic value of AURKA protein expression in liver metastases of CRC patients who underwent hemihepatectomy with curative intent. Patients and Methods: Tissue microarrays (TMAs) were generated from formalin-fixed paraffin-embedded CRCLM of 507 patients who underwent hemihepatectomy in the Netherlands between 1990 and 2010. Matched primary CRC tissue was collected of 234 patients. TMAs were stained for AURKA by immunohistochemistry, nuclear expression of neoplastic cells was assessed and subsequently associated with patient overall survival (OS) in a training and validation set. Results: High AURKA expression in CRCLM was associated with poor OS in a univariate analysis (HRR 1.68; 95%CI 1.04-2.73; P=0.03) and upon correction for established prognostic clinicopathological variables (HRR 1.77; 95%CI 1.02-3.08; P=0.04). Furthermore, AURKA expression in liver metastases was correlated to its expression in corresponding primary CRC (P=0.0002). Conclusion and Discussion: AURKA protein expression is a molecular biomarker with prognostic value for CRC patients with liver metastasis, independent of established clinicopathological variables. This study opens novel opportunities to investigate AURKA inhibitors for personalized therapy. Citation Format: Jeroen A C M Goos, Veerle M H Coupé, Begoña Diosdado, Pien M. Delis-van Diemen, Cemile Karga, Jeroen A.M. Beliën, Beatriz Carvalho, M. Petrousjka van den Tol, Henk M W Verheul, Albert A. Geldof, Gerrit A. Meijer, Otto S. Hoekstra, Remond J A Fijneman. Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1151. doi:10.1158/1538-7445.AM2013-1151

Background: Colorectal cancer (CRC) is the second leading cause of cancer mortality in developed countries, which is mainly due to hematogenous dissemination to the liver. Resection of CRC liver metastases (CRCLM) is the only treatment option with curative intent. Patient eligibility relies on standard prognostic clinicopathological variables, however, 5-year survival rates hardly exceed 40% indicating the need for better prognostic biomarkers to improve clinical management of CRCLM patients. Overexpression of hypoxia-inducible factor 1α (HIF1α), glucose transporter 1 (SLC2A1; also known as GLUT1) and vascular endothelial growth factor A (VEGFA) have been associated with tumor progression and poor prognosis of CRC patients. Aim: To investigate the individual and combined prognostic value of HIF1α, SLC2A1 and VEGFA in a multi-institutional cohort of patients with resected colorectal cancer liver metastasis (CRCLM). Methods: Tissue microarrays were generated using CRCLM and patient-matched primary CRC from patients who underwent CRCLM resection between 1990 and 2010. Prognostic value of HIF1α, SLC2A1 and VEGFA was determined by immunohistochemistry. A 500-fold cross-validated hazard rate ratio (HRRav) for overall survival was calculated. Results: Protein expression of HIF1α, SLC2A1 and VEGFA could be evaluated in 328, 350 and 335 patients, respectively. HIF1α expression was not associated with survival. High SLC2A1 expression was associated with good prognosis (HRRav0.67; P(HRR&amp;gt;1)&amp;lt;.01) and high VEGFA expression to poor prognosis (HRRav1.84; P(HRR&amp;lt;1) = .02), also after multivariate analysis including established clinicopathological prognostic variables (HRRav0.67; P(HRR&amp;gt;1)&amp;lt;.01 and HRRav1.50; P(HRR&amp;lt;1) = .02, respectively). SLC2A1 showed prognostic value in patients who were treated with systemic therapy (P&amp;lt;.01), while the prognostic value of VEGFA expression was mainly observed in patients who were not treated with systemic therapy (P&amp;lt;.01). Poorest prognosis was observed in patients with both low SLC2A1 and high VEGFA expression (P&amp;lt;.01). Conclusions: VEGFA and SLC2A1 expression are prognostic molecular biomarkers for CRCLM patients with added value to established clinicopathological variables. VEGFA is a key molecular target for anti-angiogenesis therapy in metastatic CRC patients, and SLC2A1 increases the uptake of glucose which is visualized by 18FDG-PET imaging. Therefore, these biomarkers provide opportunities to improve clinical management of CRCLM patients. Citation Format: Jeroen A.C.M. Goos, Erienne M.V. de Cuba, Veerle M.H. Coupe, Begona Diosdado, Pien M. Delis-van Diemen, Cemile Karga, Jeroen A.M. Belien, C. Willemien Menke - Van der Houven van Oordt, Albert A. Geldof, Gerrit A. Meijer, Otto S. Hoekstra, Remond J. A. Fijneman, on behalf of the DeCoDe PET group. VEGFA and SLC2A1 are prognostic biomarkers for patients with resectable colorectal cancer liver metastases. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3419. doi:10.1158/1538-7445.AM2015-3419

Seed or soil: Tracing the immune subsets in metastatic tumors.

This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells. The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases. 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis. M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.

Sialylated IgG-activated integrin β4-Src-Erk axis stabilizes c-Myc in a p300 lysine acetyltransferase-dependent manner to promote colorectal cancer liver metastasis.

Aberrant expression of musashi2 (MSI‐2) has been detected in several malignancies. However, its role in the progression of colorectal cancer (CRC) remains unknown. Our study was designed to investigate the expression and prognostic significance of MSI‐2 protein in patients with colorectal cancer. The expression of MSI‐2 was detected in 164 patients’ colorectal cancer and control specimens by the tissue microarray technique and immunohistochemical staining. The correlations between MSI‐2 expression and clinicopathological variables including overall survival were analyzed. The prognostic value of liver metastasis is evaluated by logistic regression and receiver operating characteristic (ROC) analysis. MSI‐2 was highly expressed in 32.9% (54/164) of the colorectal cancer. Overexpression of MSI‐2 was associated with depth of invasion, lymph node metastasis, distant metastasis, liver metastasis, Tumor Node Metastasis (TNM) clinical stage, and Carcinoembryonicantigen (CEA) level (P = 0.040, 0.014, <0.001, <0.001, 0.003, and 0.002, respectively). In the Cox multivariate test, MSI‐2 overexpression, lymph node metastasis, and distant metastasis were found to be the independent prognostic factors (P = 0.027, 0.010, and 0.001, respectively). Further logistic regression suggested that TNM stage and MSI‐2 high expression were related to liver metastasis in colorectal cancer patients. Conclusively, our study indicates that MSI‐2 overexpression is associated with an unfavorable prognosis and may be a potential biomarker for liver metastasis in colorectal cancer patients.

Backgrounds: Hematogenous dissemination is a prevalent route of colorectal cancer (CRC) metastasis, whereas the underlying mechanism is unclear. Tumor pericytes (TPCs) are important components of tumor vessels, which are attached to the endothelial cells and embedded within the walls of capillaries. However, as the gatekeeper of vessels, the role of TPCs in hematogenous metastasis remains largely unknown. Here, we aimed to investigate the heterogeneity of TPCs and their effects on CRC metastasis. Methods: TPCs were first isolated from the primary CRC tissues using microdissection combined with pericyte medium-based approach. Then, TPCs derived from CRC liver-metastatic (CRCLM) and CRC non-metastatic (CRCNM) patients were analyzed by single-cell RNA sequencing (scRNA-seq). Clinical CRC specimens were collected to analyze the association between the molecular profiling of TPCs and CRC metastasis. The mechanisms by which TCF21 regulated perivascular matrix remodeling and integrin α5 modulated TCF21 DNA hypermethylation were investigated using RNA-sequencing, chromatin immunoprecipitation-sequencing and bisulfite-sequencing. Pericyte-conditional Tcf21-knockout mice were constructed to investigate the effects of TCF21 in TPCs on CRC metastasis. Masson staining, atomic force microscopy, second-harmonic generation and two-photon fluorescence microscopy were employed to observe perivascular extracellular matrix (ECM) remodeling. Pericyte TCF21-targeting peptide was designed by AlphaFold and its mechanisms were examined by microscale thermophoresis. Results: Thirteen TPC subpopulations were identified by scRNA-seq. A novel subpopulation of TCF21high TPCs was found to bed associated with liver metastasis in CRC patients. Genes highly-expressed in TCF21high TPCs were enriched in ECM and ECM remodeling, thus termed as matrix pericytes. TCF21 in TPCs increased perivascular ECM stiffness, collagen rearrangement and basement membrane degradation, establishing a perivascular metastatic microenvironment to instigate CRC liver metastasis. Mechanistic studies indicated that loss of integrin α5 inhibited the FAK/PI3K/AKT/DNMT1 axis to impair TCF21 DNA hypermethylation in TCF21high TPCs. Conditional deletion of Tcf21 in TPCs or pharmacological blocking the transcriptional activity of TCF21 in TPCs could mitigate perivascular ECM remodeling and CRC liver metastasis. Conclusions: This study first uncovers the heterogeneity of TPCs during CRC liver metastasis and reveals a novel mechanism that TPCs drive CRC liver metastasis through remodeling perivascular matrix, which provides a potential diagnostic marker and therapeutic target for CRC metastasis. Citation Format: Xiaobo Li, Jinghua Pan, Qun Miao, Xiaoyu Wu, Zhan Zhao, Yihai Cao, Minfeng Chen, Dongmei Zhang, Wencai Ye. Pericytes promote colorectal cancer metastasis by remodeling perivascular matrix [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1307.

Using our data set (GSE50760) previously established by RNA sequencing, the present study aimed to identify upregulated genes associated with colorectal cancer (CRC) liver metastasis (CLM) and verify their biological behavior. The potential roles of candidate genes in tumors were assessed using cell proliferation and invasion assays. Tissue samples were collected from 18 CRC patients with synchronous CLM and two CRC cell lines (SW480 and SW620) were used for transfection and cloning. The roles of the genes identified in CLM were verified using immunohistochemistry in 48 nude mice after intrasplenic transplantation of CRC cells. mRNA and protein expression was determined by quantitative real-time reverse transcription polymerase chain reaction and western blot, respectively. Nine genes were initially selected according to the relevance of their molecular function and biological process and, finally, ALDH1A1 and IGFBP1 were chosen based on differential mRNA expression and a positive correlation with protein expression. The overexpression of ALDH1A1 and IGFBP1 significantly and time-dependently decreased cell proliferation (p ≤ 0.001–0.003) and suppressed invasiveness by ≥3-fold over control cells (p < 0.001) in the SW480 cell line, whereas they had a slight effect on reducing SW620 cell proliferation. The protein expression levels of E-cadherin, N-cadherin, claudin-1, and vimentin were significantly higher in CLM than in primary tumor tissues (p < 0.05). However, the cadherin switch, namely, N-cadherin overexpression with reduced E-cadherin expression, was not observed in CLM tissues and transfected CRC cells. Irrespective of reduced proliferation and invasion found on in vitro cell assays, persistent overexpression of β-catenin, vimentin, and ZO-1 in IGFBP1-overexpressing SW480 cells possibly contributed to CLM development in mice implanted with IGFBP1-overexpressing SW480 cells (CLM occurrences: SW480/IGFBP1-transfected mice vs. SW480/vector- and SW480/ALDH1A1-transfected mice, 4/8 vs. 0/10, p = 0.023). In conclusion, ALDH1A1 and IGFBP1 are differentially overexpressed in CLM and may play a dual role, functioning as both tumor suppressors and metastasis promoters in CRC.

This study aimed to investigate the prevalence, risk, and prognostic factors for synchronous liver metastasis (LM) in colorectal cancer (CRC) and to construct nomogram for predicting occurrence and prognosis of synchronous LM. A total of 203,998 CRC patients who were registered in the SEER database between 2010 and 2016 were included. Logistic regression was used to analyze risk factors and Kaplan-Meier was used to estimate the overall survival of CRC patients with LM. Potential prognostic factors were identified by multivariable Cox regression. For predicting the risk for development and prognosis in CRC patients with LM, we constructed nomogram and the predictive performance was estimated by the receiver operating characteristics cure, the concordance index, and calibration curve. In total, 15.3% of the CRC patients (N = 31,288) had synchronous LM. Male gender, black, uninsured status, left colon, T4/T1, and bone and lung metastases were positively associated with synchronous LM risk. The 1-year, 3-year, and 5-year overall survival rate was 49.1%, 18.4%, and 9.2%, respectively. Older age, male gender, black, uninsured status, poor histological differentiation, lymphatic metastasis, T4/T1, positive carcinoembryonic antigen, and lung, bone, and brain metastases were associated with the overall survival. Nomogram was constructed to predict the development and prognosis of synchronous LM and both of them were proved to have good calibration and discrimination. LM is highly prevalent in CRC patients. Nomogram basing on the risk and prognostic factors for synchronous LM was proved to have good performance for predicting the probability of LM occurrence and prognosis.

To investigate PIK3CA, PTEN status in the primary lesion of colorectal cancer (CRC): relationship with occurrences of liver metastasis and its prognosis. Patients with CRC who had the primary tumor resected between 2003 and 2008 were selected and enrolled into three groups according to the occurrence of liver metastasis. The mutations of PIK3CA exon 9 and 20, PTEN exon 5, 7, 8 in primary cancer cells in formalin-fixed, paraffin-embedded specimens were detected by Pyrosequencing, then a statistical analysis was deduced to find out the relationship between PIK3CA, PTEN status and occurrences of liver metastasis as well as the prognosis. Of all the 300 CRC cases, the mutation rates of PIK3CA and PTEN was 18.2% (51/300) and 16.3% (49/300). The multivariate Logistic analysis revealed that exon 5 mutation of PTEN was one of the independent risk factors of occurrence of metachronous liver metastasis in CRC patients (HR = 1.634, 95%CI: 1.796 - 3.355, P = 0.041). Patients with PTEN mutation had a poorer overall survival in group with synchronous liver metastasis (median survival time 62.0 months vs 71.0 months, χ(2) = 12.942, P = 0.048) while CRC patients who had the liver metastasis resected in group of synchronous and metachronous liver metastasis had a poorer disease free survival rates with PIK3CA mutation (median survival time 16.0 months vs 25.0 months, χ(2) = 9.679, P = 0.037). The exon 5 mutation of PTEN of CRC is potentially correlated with the occurrence of synchronous liver metastasis. CRC patients who had the liver metatasis resected but with PIK3CA mutation could have a poorer prognosis.