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Colorectal cancer (CRC) is the third most prevalent and second most lethal cancer globally, with gene mutations and tumor metastasis contributing to its poor prognosis. Single-cell sequencing technology enables high-throughput analysis of the genome, transcriptome, and epigenetic landscapes at the single-cell level. It offers significant insights into analyzing the tumor immune microenvironment, detecting tumor heterogeneity, exploring metastasis mechanisms, and monitoring circulating tumor cells (CTCs). This article provides a brief overview of the technical procedure and data processing involved in single-cell sequencing. It also reviews the current applications of single-cell sequencing in CRC research, aiming to enhance the understanding of intratumoral heterogeneity, CRC development, CTCs, and novel drug targets. By exploring the diverse molecular and clinicopathological characteristics of tumor heterogeneity using single-cell sequencing, valuable insights can be gained into early diagnosis, therapy, and prognosis of CRC. Thus, this review serves as a valuable resource for identifying prognostic markers, discovering new therapeutic targets, and advancing personalized therapy in CRC. [ABSTRACT FROM AUTHOR]

Background: We performed this study to identify predictive factors for lymph node metastasis (LNM) and analyze the impact of LNM on the prognosis of patients with T1-2 colorectal cancer (CRC), with the intention of providing guidance for the treatment. Methods: The Surveillance Epidemiology and End Result database was used to identify 20,492 patients diagnosed with T1-2 stage CRC between 2010 and 2019, who underwent surgery and lymph node evaluation and had complete prognostic information. Clinicopathological data of patients with T1-2 stage colorectal cancer treated with surgery at Peking University People's Hospital from 2017 to 2021 with complete clinical information were retrieved. We identify and confirm the risk factors for positive lymph node involvement, and the results of follow-up were analyzed. Results: Age, preoperative carcinoembryonic antigen (CEA) level, perineural invasion, and primary tumor site were independent risk factors for LNM in T1-2 CRC based on the analysis of the SEER database, while tumor size and histology of mucinous carcinoma were also independent risk factors in T1 CRC. We then make the nomogram model for predicting LNM risk and showed an acceptable consistency and calibration capability. Survival analysis showed that LNM was an independent prognostic indicator of 5-year disease-specific survival (P = 0.013) and disease-free survival (P < 0.001) in patients with T1 and T2 CRC. Conclusion: Age, CEA level and primary tumor site should be taken into consideration before making the surgical decision in T1-2 CRC patients. The tumor size and histology of mucinous carcinoma also need to be thought about in T1 CRC. Conventional imaging tests do not appear to provide a precise assessment for this issue. [ABSTRACT FROM AUTHOR]

The biological role of the spen paralogue and orthologue C-terminal domain containing 1 (SPOCD1) has been investigated in human malignancies, but its function in colorectal cancer (CRC) is unclear. This study investigated the association between SPOCD1 expression and clinicopathological features of CRC cases, as well as its prognostic value and biological function based on large-scale databases and clinical samples. The results showed that the expression level of SPOCD1 was elevated in CRC, which was generally associated with shortened survival time and poor clinical indexes, including advanced T, N, and pathologic stages. Multivariate Cox regression analysis showed that elevated SPOCD1 expression was an independent factor for poor prognosis in CRC patients. Functional enrichment analysis of SPOCD1 and its co-expressed genes revealed that SPOCD1 could act as an oncogene by regulating gene expression in essential functions and pathways of tumorigenesis, such as extracellular matrix organization, chemokine signaling pathways, and calcium signaling pathways. In addition, immune cell infiltration results showed that SPOCD1 expression was associated with various immune cells, especially macrophages. Furthermore, our findings suggested a possible function for SPOCD1 in the polarization of macrophages from M1 to M2 in CRC. In conclusion, SPOCD1 is a promising diagnostic and prognostic marker for CRC, opening new avenues for research and treatment. [ABSTRACT FROM AUTHOR]

Background: As the most widespread mRNAs modification, N6‐methyladenosine (m6A) is dynamically and reversibly modulated by methyltransferases and demethylases. ALKBH5 is a major demethylase, and plays vital roles in the progression of cancers. However, the role and mechanisms of ALKBH5 in colorectal cancer (CRC) is unclear. Results: Herein, we discovered that in CRC, downregulated ALKBH5 was closely related to poor prognosis of CRC patients. Functionally, our results demonstrated that knockdown of ALKBH5 enhanced the proliferation, migration and invasion of LOVO and RKO in vitro, while overexpression of ALKBH5 inhibited the functions of these cells. The results also demonstrated that knockdown of ALKBH5 promoted subcutaneous tumorigenesis of LOVO in vivo, while overexpression of ALKBH5 suppressed this ability. Mechanistically, results from joint analyses of MeRIP‐seq and RNA‐seq indicated that PHF20 mRNA was a key molecule that was regulated by ALKBH5‐mediated m6A modification. Further experiments indicated that ALKBH5 may inhibit stability of PHF20 mRNA by removing the m6A modification of PHF20 mRNA 3′UTR. Conclusions: ALKBH5 suppresses CRC progression by decreasing PHF20 mRNA methylation. ALKBH5‐mediated m6A modification of PHF20 mRNA can serve as a hopeful strategy for the intervention and treatment of CRC. [ABSTRACT FROM AUTHOR]

Objective: Postoperative bowel obstruction was one of the most severe complications in patients who received colorectal surgeries. This study aimed to explore risk factors of early postoperative obstruction and to construct a nomogram to predict the possibility of occurrence.Methods: The records of 1437 patients who underwent elective colorectal surgery in Peking University People's Hospital from 2015 to 2020 were retrospectively collected. Risk factors of early postoperative bowel obstruction were identified by logistic regression analysis and a nomogram was then constructed. Bootstrap was applied to verify the stability of the model.Results: COPD, hypothyroidism, probiotic indications, duration of antibiotics, and time to postoperative feeding were identified as independent risk factors and were put into a nomogram for predicting early postoperative bowel obstruction. The nomogram showed robust discrimination, with the area under the receiver operating characteristic curve was 0.894 and was well-calibrated.Conclusion: A nomogram including independent risk factors of COPD, hypothyroidism, probiotic indications, duration of antibiotics, and time to postoperative feeding were established to predict the risk of early postoperative bowel obstruction. [ABSTRACT FROM AUTHOR]

Accumulating evidence has demonstrated that N6-methyladenosine (m6A) plays important roles in various cancers, making it essential to profile m6A modifications at a transcriptome-wide scale in colorectal cancer (CRC). In the present study, we performed high-throughput sequencing to determine the m6A methylome in CRC. We obtained six pairs of CRC samples and tumour-adjacent normal tissues from Peking University People's Hospital. We used MeRIP-seq to determine that compared to the tumour-adjacent normal tissues, the CRC samples had 1343 dysregulated m6A peaks, and 625 m6A peaks were significantly upregulated and 718 m6A peaks were significantly downregulated. Genes with altered m6A peaks play critical roles in regulating glucose metabolism, RNA metabolism, and cancer stem cells. Furthermore, we identified 297 hypermethylated m6A peaks and 328 hypomethylated m6A peaks in mRNAs through conjoint analyses of MeRIP-seq and RNA-seq data. After analysing these genes with differentially methylated m6A peaks and synchronously differential expression, we identified four genes (WDR72, SPTBN2, MORC2, and PARM1) that were associated with prognosis of colorectal cancer patients by searching The Cancer Genome Atlas (TCGA). Our study suggests that m6A modifications play important roles in tumour progression and survival of CRC patients. The results also indicate that modulating m6A modifications may represent an alternative strategy to predict the survival of cancer patients and interfere with tumour progression in the future. [ABSTRACT FROM AUTHOR]

Abnormal expression of RNA binding proteins (RBPs) has been reported across various cancers. However, the potential role of RBPs in colorectal cancer (CRC) remains unclear. In this study, we performed a systematic bioinformatics analysis of RBPs in CRC. We downloaded CRC data from The Cancer Genome Atlas (TCGA) database. Our analysis identified 242 differentially expressed RBPs between tumor and normal tissues, including 200 upregulated and 42 downregulated RBPs. Next, we found eight RBPs (RRS1, PABPC1L, TERT, SMAD6, UPF3B, RP9, NOL3, and PTRH1) related to the prognoses of CRC patients. Among these eight prognosis-related RBPs, four RBPs (NOL3, PTRH1, UPF3B, and SMAD6) were selected to construct a prognostic risk score model. Furthermore, our results indicated that the prognostic risk score model accurately predicted the prognosis of CRC patients [area under the receiver operating characteristic curve (AUC)for 3- and 5-year overall survival (OS) and was 0.645 and 0.672, respectively]. Furthermore, we developed a nomogram based on a prognostic risk score model. The nomogram was able to demonstrate the wonderful performance in predicting 3- and 5-year OS. Additionally, we validated the clinical value of four risk genes in the prognostic risk score model and identified that these risk genes were associated with tumorigenesis, lymph node metastasis, distant metastasis, clinical stage, and prognosis. Finally, we used the TIMER and Human Protein Atlas (HPA)database to validate the expression of four risk genes at the transcriptional and translational levels, respectively, and used a clinical cohort to validate the roles of NOL3 and UPF3B in predicting the prognosis of CRC patients. In summary, our study demonstrated that RBPs have an effect on CRC tumor progression and might be potential prognostic biomarkers for CRC patients. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs), such as miR-654-3p, regulate gene expression at the post-transcriptional level affecting malignant tumor behavior. However, the expression levels, function, and mechanism of miR-654-3p in colorectal cancer (CRC) are unknown. Methods: The expression levels of miR-654-3p and SRC in 103 CRC tissues and matched normal colorectal tissues were detected by a quantitative real-time polymerase chain reaction (qRT-PCR). miR-654-3p was overexpressed by RNA mimics and SRC knockdown by siRNA. Function-based experiments were carried out to detect the proliferation and migration abilities in CRC cell lines. Flow cytometry assay was performed to evaluate the effect of miR-654-3p on cell apoptosis and cycle distribution. Xenograft tumor models in nude mice were utilized to evaluate miR-654-3p functions in vivo. Dual-fluorescence reporter assay was used to verify the direct binding between miR-654-3p and SRC. Results: miR-654-3p was downregulated in CRC tissues as compared to matched normal colorectal tissues. The expression levels of miR-654-3p were closely associated with distant metastasis. In addition, elevated expression of miR-654-3p in CRC patients prolonged the overall survival. Upregulated miR-654-3p significantly suppressed the proliferation and migration capacity of CRC cells by enhancing apoptosis and promoting G0/G1 phase arrest. The direct binding between miR-654-3p and SRC was verified by the dual-luciferase reporter gene. Furthermore, the suppression of proliferation and migration capacity by elevated miR-654-3p level could be reversed by overexpressing SRC. Conclusion: miR-654-3p acts as a tumor suppressor through regulating SRC. It might also serve as a diagnostic and prognostic indicator and a novel molecular target for CRC therapy. [ABSTRACT FROM AUTHOR]

Purpose: Developing an MRI-based radiomics model to effectively and accurately predict the predominant histopathologic growth patterns (HGPs) of colorectal liver metastases (CRLMs). Materials and Methods: In this study, 182 resected and histopathological proven CRLMs of chemotherapy-naive patients from two institutions, including 123 replacement CRLMs and 59 desmoplastic CRLMs, were retrospectively analyzed. Radiomics analysis was performed on two regions of interest (ROI), the tumor zone and the tumor-liver interface (TLI) zone. Decision tree (DT) algorithm was used for radiomics modeling on each MR sequence, and fused radiomics model was constructed by combining the radiomics signature of each sequence. The clinical and combination models were developed through multivariate logistic regression method. The performance of the developed models was assessed by receiver operating characteristic (ROC) curves with indicators of area under curve (AUC), accuracy, sensitivity, and specificity. A nomogram was constructed to evaluate the discrimination, calibration, and usefulness. Results: The fused radiomicstumor and radiomicsTLI models showed better performance than any single sequence and clinical model. In addition, the radiomicsTLI model exhibited better performance than radiomicstumor model (AUC of 0.912 vs. 0.879) in internal validation cohort. The combination model showed good discrimination, and the AUC of nomogram was 0.971, 0.909, and 0.905 in the training, internal validation, and external validation cohorts, respectively. Conclusion: MRI-based radiomics method has high potential in predicting the predominant HGPs of CRLM. Preoperative non-invasive identification of predominant HGPs could further explore the ability of HGPs as a potential biomarker for clinical treatment strategy, reflecting different biological pathways. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) play pivotal roles in various kinds of human diseases, especially in cancer. However, regulatory role, clinical significance and underlying mechanisms of lncRNAs in colorectal cancer (CRC) liver metastasis still remain largely unknown. This study aimed to report a novel lncRNA, lnc-HSD17B-11:1, and its functional role in CRC progression. Materials and methods: Differentially expressed lnc-HSD17B11-1:1 was screened and identified from a lncRNA profile microarray. Quantitative real-time PCR was used to determine the expression levels and prognostic values of lncRNA in CRC cohorts. In vitro and in vivo functional experiments were performed to investigate the effects of lnc-HSD17B11-1:1 on tumor growth and metastasis in CRC. Mechanistically, Base Scope, bioinformatics analyses, dual luciferase reporter assay and RNA immunoprecipitation experiments were performed to confirm the association of lnc-HSD17B11-1:1 and miR-338-3p. Dual luciferase reporter assay, qRT-PCR and western blot analysis were performed to assess the relationships among lnc-HSD17B11-1:1, miR-338-3p, and MACC1. Results: Evidently up-regulation of lnc-HSD17B11-1:1 in CRC primary tissues was correlated with the depth of invasion (p = 0.043), clinical stage (p = 0.027), distant metastasis (p = 0.003) and poor prognosis of patients with CRC. lnc-HSD17B11-1:1 promoted CRC cell proliferation, mobility and invasion in vitro and in vivo. Mechanistic analysis revealed that lnc-HSD17B11-1:1 may act as a competing endogenous RNA (ceRNA) by acting as a sponge for miR-338-3p to upregulate the expression of MACC1. Conclusion: These findings suggest that lnc-HSD17B11-1:1 promotes CRC progression through lnc-HSD17B11-1:1/miR-338-3p/MACC1 axis and this might serve as a new diagnostic marker or target for treatment of CRC. [ABSTRACT FROM AUTHOR]

Protein lysine acetylation affects colorectal cancer (CRC) distant metastasis through multiple pathways. In a previous proteomics screen, we found that isocitrate dehydrogenase 1 (IDH1) is hyperacetylated in CRC primary tumors and liver metastases. Here, we further investigate the function of IDH1 hyperacetylation at lysine 224 in CRC progression. We find that IDH1 K224 deacetylation promotes its enzymatic activity and the production of α‐KG, and we identify sirtuin‐2 (SIRT2) as a major deacetylase for IDH1. SIRT2 overexpression significantly inhibits CRC cell proliferation, migration, and invasion. IDH1 acetylation is modulated in response to intracellular metabolite concentration and regulates cellular redox hemostasis. Moreover, IDH1 acetylation reversely regulates HIF1α‐dependent SRC transcription which in turn controls CRC progression. Physiologically, our data indicate that IDH1 deacetylation represses CRC cell invasion and migration in vitro and in vivo, while the hyperacetylation of IDH1 on K224 is significantly correlated to distant metastasis and poor survival of colorectal cancer patients. In summary, our study uncovers a novel mechanism through which SIRT2‐dependent IDH1 deacetylation regulates cellular metabolism and inhibits liver metastasis of colorectal cancer. Synopsis: SIRT2 inhibits colorectal cancer cell invasion and metastasis by regulating IDH1 acetylation on K224. SIRT2 deacetylates IDH1 on Lys224 in colorectal cancer.IDH1 K224 acetylation activates HIF1α/SRC axis to promote colorectal cancer metastasis.IDH1 acetylation predicts poor prognosis in colorectal cancer. [ABSTRACT FROM AUTHOR]

Objective To establish predicting models of surgical complications in elderly colorectal cancer patients. Background Surgical complications are usually critical and lethal in the elderly patients. However, none of the current models are specifically designed to predict surgical complications in elderly colorectal cancer patients. Methods Details of 1008 cases of elderly colorectal cancer patients (age ≥ 65) were collected retrospectively from January 1998 to December 2013. Seventy-six clinicopathological variables which might affect postoperative complications in elderly patients were recorded. Multivariate stepwise logistic regression analysis was used to develop the risk model equations. The performance of the developed model was evaluated by measures of calibration (Hosmer-Lemeshow test) and discrimination (the area under the receiver-operator characteristic curve, AUC). Results The AUC of our established Surgical Complication Score for Elderly Colorectal Cancer patients (SCSECC) model was 0.743 (sensitivity, 82.1%; specificity, 78.3%). There was no significant discrepancy between observed and predicted incidence rates of surgical complications (AUC, 0.820; P = .812). The Surgical Site Infection Score for Elderly Colorectal Cancer patients (SSISECC) model showed significantly better prediction power compared to the National Nosocomial Infections Surveillance index (NNIS) (AUC, 0.732; P ˂ 0.001) and Efficacy of Nosocomial Infection Control index (SENIC) (AUC; 0.686; P˂0.001) models. Conclusions The SCSECC and SSISECC models show good prediction power for postoperative surgical complication morbidity and surgical site infection in elderly colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Several studies have shown that metabolic syndrome (MS) was a risk factor for colorectal cancer, but few studies have reported the relationship between MS and the prognosis of colorectal cancer. Methods: Data were collected from 507 cases of colorectal carcinoma between January 2002 and March 2007 to establish the database. These patients were divided into 2 groups based on the presence of MS. We tested the prognostic value of MS in the patients. The risk of adverse events was examined by Cox proportional hazard modeling. Results: The rates of liver metastasis and tumor recurrence were higher in the group of patients with colorectal cancer accompanied by MS. Moreover, MS is one of the important elements that independently can influence the survival (colonic carcinoma: hazard ratio [HR], 1.633; 95% confidence interval [CI], 1.039–2.565; rectal carcinoma: HR, 1.939, 95% CI, 1.076–3.494) and liver metastasis (colonic carcinoma: HR, 2.619; 95% CI, 1.288–5.324; rectal carcinoma: HR, 2.814; 95% CI, .962–2.888) of both colonic and rectal carcinoma patients, and MS patients have the highest risk with worse survival and liver metastases compared with other parameters. Conclusions: The results suggest that MS may be an important prognostic factor for colorectal cancer, decreasing the incidence of MS may improve the therapeutic efficacy of colorectal cancer. [Copyright &y& Elsevier]

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and been extensively used for patients with metastastic colorectal cancer (mCRC), especially those harboring deficient mismatch repair/ microsatellite instability (dMMR/MSI). However, the majority of mCRC are classified as proficient mismatch repair/microsatellite stability(pMMR/MSS) type characterized by a cold immune microenvironment, rendering them generally unresponsive to ICIs. How to improve the efficacy of ICIs for these patients is an important issue to be solved. On the one hand, it is urgent to discover the predictive biomarkers and clinical characteristics associated with effectiveness and expand the subset of pMMR/MSS mCRC patients who benefit from ICIs. Additionally, combined strategies are being explored to modulate the immune microenvironment of pMMR/MSS CRC and facilitate the conversion of cold tumors into hot tumors. In this review, we have focused on the recent advancements in the predictive biomarkers and combination therapeutic strategies with ICIs for pMMR/MSS mCRC. [Display omitted] • ICIs have enduring advantages for dMMR/MSI mCRC. However, the resistance to ICIs among the pMMR/MSS subgroup is prevalent. • The identification of predictive biomarkers and exploration of combined strategies carry significant implications. • The identification of novel biomarkers for predicting efficacy holds promise for expanding the beneficiaries. • The combined strategies aimed at transforming "cold" tumors into "hot" tumors will generate new prospects for pMMR/MMS CRC. [ABSTRACT FROM AUTHOR]

Standard treatment of colorectal cancer (CRC) improves the prognosis of CRC patients, but it is still intractable to control the progression of metastatic CRC. Immune microenvironment and immunotherapies of CRC have received extensive attention in recent years, but present immunotherapies of CRC have mainly focused on T cells and therapeutic response is only observed in a small proportion of patients. Innate immune cells are the first-line of defense in the development of malignancies. Natural killer (NK) cells, NKT cells and γδT cells are three types of innate cells of lymphoid origin and show cytotoxicity against various tumor cells including CRC. Besides, in the development of CRC, they can also be inhibited or express regulatory type, promoting tumor progression. Researches about anti-tumorigenic and pro-tumorigenic mechanisms of these cells are ongoing and regulation of these cells is also being unearthed. Meanwhile, immunotherapies using these cells more or less have shown efficacy in animal models and some of them are under exploration in clinical trials. This review provides an overview of intrinsic properties of NK cell, NKT cell and γδT cell, and summarizes current related promising treatment strategies. [ABSTRACT FROM AUTHOR]

Lysine acetylated modification was indicated to impact colorectal cancer (CRC)’s distant metastasis. However, the global acetylated proteins in CRC and the differential expressed acetylated proteins and acetylated sites between CRC primary and distant metastatic tumor remains unclear. Our aim was to construct a complete atlas of acetylome in CRC and paired liver metastases. Combining high affinity enrichment of acetylated peptides with high sensitive mass spectrometry, we identified 603 acetylation sites from 316 proteins, among which 462 acetylation sites corresponding to 243 proteins were quantified. We further classified them into groups according to cell component, molecular function and biological process and analyzed the metabolic pathways, domain structures and protein interaction networks. Finally, we evaluated the differentially expressed lysine acetylation sites and revealed that 31 acetylated sites of 22 proteins were downregulated in CRC liver metastases compared to that in primary CRC while 40 acetylated sites of 32 proteins were upregulated, of which HIST2H3AK19Ac and H2BLK121Ac were the acetylated histones most changed, while TPM2 K152Ac and ADH1B K331Ac were the acetylated non-histones most altered. These results provide an expanded understanding of acetylome in CRC and its distant metastasis, and might prove applicable in the molecular targeted therapy of metastatic CRC. Biological significance This study described provides, for the first time, that full-scale profiling of lysine acetylated proteins were identified and quantified in colorectal cancer (CRC) and paired liver metastases. The novelty of the study is that we constructed a complete atlas of acetylome in CRC and paired liver metastases. Moreover, we analyzed these differentially expressed acetylated proteins in cell component, molecular function and biological process. In addition, metabolic pathways, domain structures and protein interaction networks of acetylated proteins were also investigated. Our approaches shows that of the differentially expressed proteins, HIST2H3AK19Ac and H2BLK121Ac were the acetylated histones most changed, while TPM2 K152Ac and ADH1B K331Ac were the acetylated non-histones most altered. Our findings provide an expanded understanding of acetylome in CRC and its distant metastasis, and might prove applicable in the molecular targeted therapy of metastatic CRC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the capability of a radiomics model, which was designed to identify histopathologic growth pattern (HGP) of colorectal liver metastases (CRLMs) based on contrast-enhanced multidetector computed tomography (ceMDCT), to predict early response and 1-year progression free survival (PFS) in patients treated with bevacizumab-containing chemotherapy.Methods: Patients with unresectable CRLMs who were treated with bevacizumab-containing chemotherapy were included in this multicenter retrospective study. For each target lesion, the radiomics-diagnosed HGP (RAD_HGP) of desmoplastic (D) pattern or replacement (R) pattern was determined. Logistic regression and receiver operating characteristic (ROC) curves were used to assess lesion- and patient-based responses according to morphologic response criteria. One-year PFS was calculated using Kaplan-Meier curves. Hazard ratios for 1-year PFS were obtained through Cox proportional hazard regression analysis.Results: Among 119 study patients, 206 D pattern and 140 R pattern lesions were identified. In patients with multiple lesions, 52 had D pattern, 31 had R pattern, and 36 had mixed (D + R) pattern. The area under the curve value for RAD_HGP in predicting early response was 0.707 for lesion-based analysis and 0.720 for patient-based analysis. Patients with D pattern had a significantly longer PFS than patients with R pattern or mixed pattern (P < 0.001). RAD_HGP was the only independent predictor of 1-year PFS.Conclusions: HGP diagnosed using a radiomics model could be used as an effective predictor of PFS for patients with CRLMs treated with bevacizumab-containing chemotherapy. [ABSTRACT FROM AUTHOR]

• The expression of TDO2 in colorectal cancer is higher than that in normal tissues. • Invasion and migration of colorectal cancer cells may be affected by the TDO2. • TDO2 may be an indicator of poor prognosis of colorectal cancer. • The expression of Kyn pathway enzymes may have a potential relationship with increased AhR activity. The aim of this study was to explore the expression levels and biological significance of TDO2 in colorectal cancer (CRC). First, we explored the potential oncogenic roles of TDO2 across 33 tumors based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Second, we evaluated TDO2 protein expression in 55 CRC tissue samples and 30 cDNA samples by immunohistochemistry and qPCR. Third, we investigated the effect of TDO2 on CRC cells by cell proliferation, wound healing, invasion, and colony formation assays. Finally, we determined the protein that is most closely associated with TDO2 via bioinformatics analysis, enriched the key pathways, and verified them. The expression level of TDO2 was found to be associated with the tumor clinical stage in CRC. A high expression of TDO2 was associated with a poor outcome in CRC patients. Inhibition of TDO2 expression by RNAi in LoVo and HCT116 cell lines significantly reduced the proliferation, migration, and invasion abilities as well as colony formation abilities of cells. Further, knockdown of TDO2 expression induced inactivation of the TDO2–KYNU–AhR signaling pathway. The results suggest that TDO2 plays an important role in the progression of CRC. Accordingly, TDO2 is a potential therapeutic target in CRC. [ABSTRACT FROM AUTHOR]