Effective mucolytic therapy can greatly improve the efficacy of cytoreductive surgery + hyperthermic intraperitoneal chemotherapy, alleviate symptoms and improve prognosis for pseudomyxoma peritonei (PMP) patients. The main components of PMP mucus are highly O-glycosylated proteins called mucins. Represented by mucin2 (MUC2), mucins are the source of mucus viscoelasticity. This review investigated detailed processes of mucin O-glycosylation and mucolytic therapies in PMP. We introduced molecular pathological mechanism of PMP, types of mucus and mucins in PMP, molecular structure and biological functions of mucins. We focus on the synthesis process and physiological functions of MUC2 O-glycosylation. Furthermore, we summarize the potential therapeutic approaches to inhibiting mucin secretion and mucolysis. Detailed process of mucin O-glycosylation in endoplasmic reticulum and Golgi apparatus was discussed. We discussed promising approaches to targeting the substrates and enzymes in O-glycosylation, including uridine diphosphate and GalNAc analogs/derivatives, ppGalNAc-T/GALNT inhibitors, disulfide bond reducing agents or PDI inhibitors, O-glycosidases, and glucoproteinases. We provide a reference for the development of PMP mucolytic therapy, and some potential therapeutic targets aiming at mucin O-glycosylation.

Background The Peritoneal Cancer Index recorded at laparotomy is based on visual and palpable inspection of peritoneal surfaces for disease. This study aimed to analyze interobserver variation in assigning the lesion score (LS) and morphologic term (MT) to characterize peritoneal lesions (PL) and predict the probability of malignancy (POM) among surgeons with expertise in cytoreductive surgery (CRS) for peritoneal malignancies. Methods The study selected 80 intraoperative images of PLs depicting different morphologic appearances of PLs arising from different primary tumors in various peritoneal regions. In the study, 50 expert peritoneal malignancy surgeons were asked to assign an LS to the region in question, select the MT or MTs to describe the PL, and predict the POM. Information on the presence of disease on histopathology was not provided at this point. Inter-observer reliability was evaluated using Krippendorff's alpha (alpha). A consensus was reached if any option received more than 75% of the votes. Results The study participants comprised 41 (82%) of 50 experts. Consensus on LS was achieved for 18 images (22.5%), with low agreement (alpha = 0.174). For MTs, a consensus was reached for 21 images (26.5%; alpha = 0.0902, denoting low and unreliable agreement. Of these 21 images, the MT used was "tumor nodule" for 90.4% of the images (p < 0.001). The POM was accurately predicted in 52.5% of the cases (alpha = 0.155). Administration of neoadjuvant chemotherapy had no impact on the surgeons' assessment of the three parameters. Conclusions Even the most experienced CRS surgeons showed high interobserver variation and unreliable agreement in the description and accurate characterization of PLs on pictorial records. A Delphi consensus to standardize the MT used and scoring of PL could reduce discordance.

Gastric cancer progression is driven by intricate crosstalk among exosomes, macrophage polarization, inflammatory dysregulation, and tumor-associated neuroinflammation within the tumor microenvironment, which collectively form a reciprocal vicious cycle. As critical intercellular mediators, exosomes derived from tumor cells, immune cells, and stem cells deliver microRNA cargos to orchestrate M1/M2 macrophage balance and modulate neuroinflammatory states, exerting either pro-tumor or anti-tumor effects. M1 macrophage-derived exosomal miRNAs suppress PD-L1 and NLRP3 signaling, reduce pro-inflammatory cytokine release, ameliorate neuroinflammation, and enhance anti-tumor immunity. Conversely, tumor cell- and M2 macrophage-derived exosomes drive M2 polarization via the MAPK/ERK and PI3K/Akt pathways, amplifying the secretion of immunosuppressive cytokines and exacerbating neuroinflammatory progression. Stem cell- and traditional Chinese medicine-derived exosomes reverse immunosuppression by targeting the STAT3 pathway, polarize macrophages toward the M1 phenotype, and attenuate tumor-associated neuroinflammation. These regulatory events converge on the NF-κB and NLRP3 inflammasome pathways to shape the inflammatory and neuroinflammatory microenvironment. Preclinical evidence confirms that exosome-based interventions reduce tumor burden by remodeling macrophage phenotypes, restoring inflammatory homeostasis, and ameliorating neuroinflammation. This review identifies exosomal regulators as promising targets for rebalancing macrophage polarization, inflammation, and neuroinflammation, providing a framework for advancing gastric cancer therapeutics.

Background: China’s digestive disease landscape is undergoing rapid epidemiologic transition, yet whether endoscopy capacity aligns with evolving population needs remains unknown. Methods: Using Global Burden of Disease 2023 data, we analysed age-standardised rates for four endoscopy-relevant conditions (stomach cancer, colorectal cancer, peptic ulcer disease, cirrhosis) in China from 1990 to 2023. We calculated estimated annual percentage change (EAPC) via log-linear regression, identified inflection points through joinpoint regression with Bayesian information criterion model selection, and translated disease burden into endoscopy demand using a procedure-specific model with Monte Carlo sensitivity analysis (10 000 triangular draws). Findings: Colorectal cancer incidence increased by 2·90% annually (95% CI 2·74–3·05), while stomach cancer and peptic ulcer disease declined. The burden-to-demand model estimated 46·1 million endoscopy procedures needed annually, including 22·5 million colonoscopies, compared with a national colonoscopy capacity of 18·3 million—a 60% structural deficit concentrated in lower endoscopy. A FIT-first screening pathway could achieve 85% population coverage within existing capacity constraints versus 38% for colonoscopy-first. Interpretation: This analysis identifies a fundamental mismatch between epidemiologic transition and endoscopy system design in China and provides a reproducible framework for aligning capacity with population needs in rapidly developing health systems.

Supplementary Figure S10. The receiver operating characteristic curve of qFIT only in the development set. ROC curve showing the discriminative ability of quantitative FIT (categorized) without clinical variables for advanced colorectal neoplasm prediction in the development set (n = 3,209; AUROC = 0.844).

ObjectiveTo develop an early postoperative rehabilitation nursing protocol for patients with peritoneal cancer following cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), and to evaluate its effectiveness.MethodsA total of 177 patients with peritoneal cancer who underwent CRS combined with HIPEC at Beijing Tsinghua Changgung Hospital, Tsinghua University from January to October 2024 were randomly assigned to control group and observation group by random number table method, with 94 and 83 cases in each group, respectively. The control group received conventional rehabilitation nursing, including basic daily care, position management, pulmonary function rehabilitation (once every two hours, twice daily, 10-15 minutes per session), bedside activities (30 minutes per session, twice daily, seven days per week), lasting for two weeks. The observation group additionally received early postoperative rehabilitation nursing protocol, targeting the improvement of postoperative dysfunction after CRS combined with HIPEC, including aerobic exercise, resistance exercise, and balance training, 60 minutes per session, twice daily, seven days per week, lasting for two weeks. Before intervention and one day prior to discharge, the Short Physical Performance Battery (SPPB) was used to evaluate physical performance by researchers blinded to group allocation; De Morton Mobility Index (DEMMI) was used to evaluate physical activity and mobility; Borg Rating of Perceived Exertion (RPE) was used to evaluate subjective fatigue; Barthel Index (BI) was used to evaluate activities of daily living; Six-Minute Walking Test (6MWT) was used to evaluate cardiopulmonary function; a pulse oximeter was used to measure blood oxygen saturation (SpO2); and a portable spirometer was used to measure forced vital capacity (FVC). The incidence of postoperative adverse events, including atelectasis, deep vein thrombosis, intestinal obstruction, arrhythmia, and falls, as well as postoperative hospital stay duration and gastric tube retention time were compared between two groups.Results(1) SPPB, DEMMI, RPE and BI scores: compared with that before intervention, SPPB, DEMMI, and BI scores in both groups increased significantly after intervention (P<0.05), while RPE score decreased significantly (P<0.05). Compared with the control group, SPPB, DEMMI, and BI scores in the observation group were significantly higher after intervention (P<0.05), while the RPE score was significantly lower (P<0.05). (2) SpO2, 6MWT and FVC: compared with that before intervention, SpO2 and 6MWT in both groups increased significantly after intervention (P<0.05), and FVC in the observation group increased significantly after intervention (P<0.05). Compared with the control group, SpO2, 6MWT and FVC scores in the observation group were significantly higher after intervention (P<0.05). (3) Postoperative hospital stay and gastric tube retention time: compared with the control group, postoperative hospital stay and gastric tube retention time in the observation group were significantly shorter (P<0.05). (4) Incidence of adverse events: there was no statistically significant difference in the incidence of adverse events between two groups (P>0.05).ConclusionThe early postoperative rehabilitation nursing protocol can effectively facilitate physical functional recovery and improve cardiopulmonary function in patients who underwent CRS combined with HIPEC, as well as reduce hospital stay duration and gastric tube retention time.

Moderate-to-severe postoperative pain is common after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Evidence that liposomal bupivacaine provides clinically important advantages over conventional local anesthetics is inconsistent, and evidence in CRS + HIPEC remains limited. This trial evaluated the incremental efficacy and safety of liposomal bupivacaine incisional infiltration added to patient-controlled intravenous analgesia (PCIA) compared with saline infiltration plus PCIA. In this single-center, randomized, participant- and assessor-blinded, placebo-controlled trial, adults aged 18–65 years scheduled for elective CRS + HIPEC were assigned 1:1 to standardized PCIA plus liposomal bupivacaine incisional infiltration (PCIA-LB) or PCIA plus normal saline infiltration (PCIA-NS). The primary endpoint was the incidence of moderate-to-severe movement-evoked incisional pain (numeric rating scale > = 4) within 72 h. The prespecified primary efficacy analysis used the per-protocol set (PPS), with a conservative intention-to-treat (ITT) sensitivity analysis. PCIA followed an institutional standard operating procedure. Monitoring was continuous in the intensive care unit (ICU); after transfer to the ward, pulse oximetry was continued through postoperative day 3, with intermittent electrocardiography and noninvasive blood pressure monitoring. The PPS included 94 patients (PCIA-NS, n = 48; PCIA-LB, n = 46). Moderate-to-severe movement-evoked pain within 72 h was less frequent with PCIA-LB than with PCIA-NS (19.6

Objective:To investigate the efficacy and safety of pemetrexed/platinum-based chemotherapy combined with or without bevacizumab after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of patients with malignant peritoneal mesothelioma (MPM). Methods:A retrospective non-randomized study was performed on 205 MPM patients treated with CRS+HIPEC at our institution. A total of 97 eligible patients were analyzed: 58 patients who received postoperative chemotherapy combined with bevacizumab (C&B) and 39 patients who received chemotherapy alone (C) were divided into a study group and a control group, respectively. The patients were also divided into the bevacizumab-exposed subgroup and the bevacizumab-unexposed subgroup based on whether they had a history of bevacizumab infusion. Clinicopathological data and follow-up information were statistically analyzed. Independent prognostic factors were identified via survival analysis, and the safety of combination therapy was assessed via adverse event analysis. Results:As of the follow-up cutoff date of July 1, 2025, in both the subgroups with and without a history of bevacizumab infusion, there was no statistically significant difference between the control and study groups in baseline pathological characteristic parameters (p > 0.05). Survival analysis revealed that in the subgroup of patients with a history of bevacizumab infusion, the difference in median overall survival (mOS) between the control and study groups was statistically significant (31.9 months vs. NR; p = 0.031), and the difference in median disease-free survival (mDFS) between the control and study groups was statistically significant (12.5 months vs. NR; p = 0.001); in the subgroup of patients without a history of bevacizumab infusion, the difference in mOS between the control and study groups was also statistically significant (20.5 months vs. NR; p = 0.001), and the difference in mDFS between the control and study groups was statistically significant (13.2 vs. 36.2 months; p = 0.001). The Cox regression model found that postoperative C&B was an independent prognostic factor (p = 0.009, HR = 0.081, 95% CI: 0.012-0.526) in the subgroup with a history of bevacizumab infusion, and the Ki-67 index (p = 0.043, HR = 2.563, 95% CI: 1.029-6.386) and postoperative C&B were independent prognostic factors (p = 0.01, HR = 0.086, 95% CI: 0.032-0.232) in the subgroup with no bevacizumab treatment history. A total of 101 cases of grade 1~2 adverse events in the study group were revealed via adverse event analysis, with common events including nausea/vomiting, fatigue, leukopenia/neutropenia, thrombocytopenia, anemia, abnormal liver function, hypertension, and proteinuria. There were four cases with grade 3 adverse events, mainly leukopenia/neutropenia, hypertension, and proteinuria. In the control group, there were 84 cases of grade 1~2 adverse events, and three cases of grade 3 adverse events were observed. Conclusion:Our exploratory findings suggest that bevacizumab combined with pemetrexed/platinum-based chemotherapy may be a therapeutic option for MPM patients after CRS+HIPEC; however, a prospective, randomized controlled clinical study is needed to validate our findings.

This study aimed to compare the efficacy and safety of perioperative somatostatin versus octreotide in peritoneal carcinomatosis (PC) patients after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC). Peritoneal cancer patients treated with CRS + HIPEC were divided into two groups (somatostatin group and octreotide group). The postoperative gastric drainage volume, levels of inflammatory factors, perioperative safety and adverse effects were compared between two groups. There were 48 (54.5

Peritoneal metastases (PM) are a significant clinical complication arising from various cancers, which is often a marker of advanced disease with poor prognosis and limited therapeutic options. Recent advances in the field of intraperitoneal (IP) therapies have shown promise in improving PM treatment outcomes, because of the advantages including superior local drug concentrations, reduced systemic toxicity, and the potential to overcome typical barriers encountered in traditional systemic therapies. Multiple clinical trials have demonstrated that IP chemotherapy (particularly hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC)), immunotherapy, and radiotherapy (often combined with immunotherapy) can significantly improve patient survival rates. Additionally, various emerging preclinical IP therapeutical strategies have been developed targeting different stages of the full medical treatment cycle, such as tumor-engineered for drug testing, fluorescent probes for diagnosis, multi-drug delivery systems for therapy. This review article focused on how IP delivery impacts the therapy of PM spanning the clinical therapeutic modes to advances in preclinical therapeutical strategies to provide new insights into their clinical applications.

Gastrointestinal cancer (GIC) remains a major clinical burden, and readily available biomarkers are needed to improve preoperative prognostic assessment and risk stratification. The present study aimed to evaluate the prognostic significance of the preoperative lactate dehydrogenase-to-albumin ratio (LAR) in patients with GIC. A comprehensive search was performed in PubMed, Embase and the Cochrane Library to identify relevant studies published from the date of database inception to March 20, 2025. The extracted outcomes included hazard ratios (HRs) for overall survival (OS) and recurrence-free survival (RFS) and odds ratios (ORs) for major postoperative complications. A total of five independent studies involving 6,379 patients were included in the present meta-analysis. A higher preoperative LAR was significantly associated with poorer OS [HR=1.90; 95% confidence interval (CI), 1.63-2.21; P<0.001]. Subgroup analysis confirmed the robustness of this association across analytical models, cancer types, countries and LAR cut-off values. A higher LAR was also associated with poorer RFS (HR=1.83; 95% CI, 1.52-2.20; P<0.001) and a higher risk of major postoperative complications (OR=2.36; 95% CI, 1.49-3.74; P<0.001). In conclusion, preoperative LAR may serve as a useful prognostic biomarker for survival outcomes in patients with GIC. Incorporating this readily available and low-cost biomarker into routine preoperative assessment may help improve perioperative risk stratification and guide postoperative management.

Purpose To develop a radiomics model based on hepatobiliary phase gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (EOB)-enhanced MRI features at the tumor margin to predict microvascular invasion in high-risk solitary hepatocellular carcinoma (HR-sHCC), determine the optimal margin region, and explore the underlying biologic mechanisms. Materials and Methods This retrospective study included patients with HR-sHCC from three medical centers between April 2015 and December 2022. Radiomics features were extracted from 121 volumes of interest (VOIs) at the tumor margin at EOB MRI. Nine combinations of statistical and machine learning methods were used to construct and validate the optimal margin region-based radiomics model. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), and patient stratification was evaluated with Kaplan-Meier and log-rank analyses. RNA sequencing data underwent differential expression analysis with DESeq2, followed by Kyoto Encyclopedia of Genes and Genomes (ie, KEGG) and Gene Ontology (ie, GO) enrichment, and immune cell infiltration was assessed using xCell and EPIC. Results A total of 436 patients (mean age, 57.7 years ± 8.8 [SD]; 352 male) were included: 254 in the training, 108 in the internal test, and 74 in the external test cohorts. Receiver operating characteristic analysis showed AUCs of 0.80 (95% CI: 0.74, 0.86), 0.76 (95% CI: 0.66, 0.85), and 0.72 (95% CI: 0.58, 0.86), respectively. The model effectively stratified patients by overall and disease-free survival (all P < .05). RNA sequencing revealed extracellular matrix remodeling, transforming growth factor-β signaling, and M2 macrophage infiltration in high optimal margin region-score tumors. Conclusion The optimal margin region-based radiomics model, derived from EOB MRI, effectively captured tumor margin heterogeneity. Keywords: MRI, Machine Learning, Radiomics, Radiogenomics, Abdomen/GI, Liver, Surgery, High-Risk Solitary Hepatocellular Carcinoma, Tumor Margin, Microvascular Invasion, Gd-EOB-DTPA-enhanced MRI, OATP1B3 © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article.

As survival of patients with breast cancer (BC) considerably improved, the incidence of breast cancer brain metastases (BCBM) is increasing. Molecular subtypes of breast cancer are important evidences for the development of follow-up strategies and systemic therapy for patients with BCBM. The study aimed to analyze the clinicopathological characteristics and identify prognostic factors for BCBM based on molecular subtype. In order to conduct a more detailed study on the clinical characteristics of brain metastases about BC, we divided them into four molecular subtypes. The clinicopathological data from 295 patients were retrospectively evaluated. COX regression analysis was used to identify the independent risk factors affecting survival following brain metastases. There were significant differences in histological grade (P < 0.001) among the four different molecular subtypes. The pathological inconsistency rate was higher for hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative BCBM (30.0

Hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly recognized as a valuable adjunct to cytoreductive surgery (CRS) in the management of ovarian cancer with peritoneal dissemination. This comprehensive review synthesizes contemporary evidence on the efficacy, safety, and future directions of HIPEC across various clinical settings, including primary, interval, and recurrent disease. Landmark studies such as the OVHIPEC-1 trial have demonstrated significant survival benefits when HIPEC is integrated into interval cytoreductive surgery following neoadjuvant chemotherapy, with improvements in both progression-free and overall survival without increasing severe morbidity. Survival gains have also been observed in upfront settings, particularly in patients with stage III epithelial ovarian cancer. However, evidence in recurrent disease remains mixed, with some trials showing benefit and others showing no significant advantage. Critical to the success of HIPEC are optimal patient selection and surgical quality, with completeness of cytoreduction (CC0/CC1), low peritoneal cancer index (PCI), and biological factors such as tumor microenvironment composition emerging as key prognostic indicators. Although HIPEC is associated with a higher incidence of grade 3–5 adverse events, particularly renal and gastrointestinal toxicities, these are generally manageable in experienced centers. Enhanced recovery protocols and careful perioperative management have further improved safety profiles. Emerging innovations include combination with normothermic intraperitoneal chemotherapy, integration of immunotherapy such as intraperitoneal nivolumab, use of paclitaxel-based regimens, and exploration of minimally invasive techniques. Future directions also involve molecular profiling, AI-driven patient selection, and synergy with targeted therapies like PARP inhibitors. Ongoing research is essential to refine protocols, standardize patient selection, and integrate HIPEC into evolving systemic treatment landscapes. In conclusion, HIPEC represents a major advancement in the multimodal treatment of advanced ovarian cancer, offering meaningful survival benefits when applied in selected patients by multidisciplinary teams.

INTRODUCTION:Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is the standard of care for pseudomyxoma peritonei (PMP) but is associated with substantial perioperative burden and prolonged recovery. Contemporary data on health-related quality of life (HRQoL) trajectories after CRS + HIPEC remain limited, as does their integration into perioperative and rehabilitation planning. We aimed to characterize short- and mid-term HRQoL changes after CRS + HIPEC in PMP and to identify ERAS-informed rehabilitation priorities based on postoperative symptom and function trajectories. METHODS:We screened 273 patients from our institutional PMP CRS + HIPEC database and included 111 adults who had adequate EORTC QLQ-C30 data for longitudinal analysis. HRQoL was assessed using the EORTC QLQ-C30 at baseline and 1 week, 1, 3, 6, 9 and 12 months postoperatively. Longitudinal changes were summarized descriptively, and mean differences versus baseline were interpreted using established minimally important difference thresholds (≥10 points). RESULTS:At 1 week postoperatively, physical, role, emotional, cognitive and social functioning and global QoL declined by 22.9, 41.6, 13.3, 19.7, 20.5 and 28.4 points, respectively, all exceeding the threshold for clinically meaningful deterioration. Fatigue, pain, dyspnoea, insomnia, appetite loss and financial difficulties showed peak or near-peak worsening at 1 week, whereas constipation and diarrhea peaked at 3 months. Overall QoL was worst around 1 month postoperatively and then improved steadily; by 12 months, most functional scales and symptoms had returned to or approached baseline (e.g. global QoL -1.1 points vs. preoperative), although mild residual cognitive and bowel disturbances persisted in some patients. DISCUSSION:CRS + HIPEC for PMP imposes a pronounced but largely transient HRQoL burden, characterized by a sharp early decline, mid-term recovery and near-restoration of baseline QoL within 6-12 months. Our findings support an ERAS-informed rehabilitation framework that prioritizes pain control, respiratory recovery, nutrition, sleep, and psychological support. These elements should be interpreted as clinically informed rehabilitation priorities rather than as a validated intervention package directly derived from this observational dataset. These findings inform preoperative counseling and the timing of follow-up after CRS + HIPEC.

Malignant peritoneal mesothelioma (MPM) is a highly aggressive peritoneal malignancy with a significant recurrence rate following cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). There is an urgent need to investigate novel therapeutic strategies for MPM. Natural killer (NK) cells exhibit rapid responsiveness in anti-tumor immunity; however, NK cells’ dynamic evolution and clinical significance in MPM remain unclear. This study retrospectively enrolled 80 newly diagnosed MPM patients (preoperative group) and 64 patients who underwent CRS + HIPEC (postoperative group). The level of NK cells (CD3−CD56dimCD16+) in peripheral blood was quantified using flow cytometry. Univariate and multivariate regression analyses were performed to evaluate the association between NK cell counts and clinicopathological characteristics, intraoperative events, and prognosis. A multivariate prediction model for NK cell recovery was established. 41 patients (51.3

tRNA-derived fragments (tRF) are a class of small noncoding RNAs that have exhibited several functions in cancer. Recent studies have shown that mutations in tRNA genes can lead to global changes in tRF expression levels and may affect tRF function, highlighting the need to further elucidate the regulation and functions of tRFs in cancer. In this study, we conducted a pan-cancer analysis of tRF quantitative trait loci (tRFQTL), encompassing 16,703 genetic variants associated with tRF expression across 31 cancer types. A joint analysis of genome-wide association study data revealed that tRFQTLs were preferentially enriched in cancer risk loci and colocalized with 106 genome-wide association study variants, explaining a substantial portion of cancer heritability. Moreover, tRFs regulated by tRFQTLs were enriched in cancer-related pathways and correlated with drug response and immune infiltration. Notably, polygenic risk score models incorporating tRFQTLs improved high-risk population identification. Investigation of large-scale population cohorts revealed a tRFQTL, rs9461276, associated with colorectal cancer risk. In biological assays, the rs9461276-C allele increased tRF-18-HSQS52D2 expression, which suppressed colorectal cancer malignant phenotypes. Mechanistically, tRF-18-HSQS52D2 bound to the 3' untranslated region of POU2F1, destabilizing the oncogenic transcript. Integrated RNA sequencing and chromatin immunoprecipitation sequencing assays indicated that POU2F1 enhanced colorectal cancer cell proliferation by activating various pathologic pathways associated with oxidative and glycolytic metabolism, mitotic stability, and cell cycle regulation. Finally, a database (Cancer-tRFQTL) was generated as a resource to support investigation into tRF-mediated mechanisms and genetic basis of tRF expression in human cancers. Overall, this study helps advance the understanding of tRFs in cancer pathogenesis. SIGNIFICANCE:Genetic variants modulating tRF expression significantly influence cancer risk, including rs9461276-C that upregulates tRF-18-HSQS52D2 to suppress its downstream oncogenic target POU2F1 and thereby inhibit colorectal cancer development. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI .