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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. Countless CRC patients undergo disease progression. As a hallmark of cancer, Warburg effect promotes cancer metastasis and remodels the tumor microenvironment, including promoting angiogenesis, immune suppression, cancer-associated fibroblasts formation and drug resistance. Targeting Warburg metabolism would be a promising method for the treatment of CRC. In this review, we summarize information about the roles of Warburg effect in tumor microenvironment to elucidate the mechanisms governing Warburg effect in CRC and to identify novel targets for therapy.

Background Lactylation, a novel contributor to post-translational protein modifications, exhibits dysregulation across various tumors. Nevertheless, its intricate involvement in colorectal carcinoma, particularly for non-histone lactylation and its intersection with metabolism and immune evasion, remains enigmatic. Methods Employing immunohistochemistry on tissue microarray with clinical information and immunofluorescence on colorectal cell lines, we investigated the presence of global lactylation and its association with development and progression in colorectal cancer as well as its functional location. Leveraging the AUCell algorithm alongside correlation analysis in single-cell RNA sequencing data, as well as cox-regression and lasso-regression analysis in TCGA dataset and confirmed in GEO dataset, we identified a 23-gene signature predicting colorectal cancer prognosis. Subsequently, we analyzed the associations between the lactylation related gene risk and clinical characteristics, mutation landscapes, biological functions, immune cell infiltration, immunotherapy responses, and drug sensitivity. Core genes were further explored for deep biological insights through bioinformatics and in vitro experiments. Results Our study innovatively reveals a significant elevation of global lactylation in colorectal cancer, particularly in malignant tumors, confirming it as an independent prognostic factor for CRC. Through a comprehensive analysis integrating tumor tissue arrays, TCGA dataset, GEO dataset, combining in silico investigations and in vitro experiments, we identified a 23-gene Lactylation-Related Gene risk model capable of predicting the prognosis of colorectal cancer patients. Noteworthy variations were observed in clinical characteristics, biological functions, immune cell infiltration, immune checkpoint expression, immunotherapy responses and drug sensitivity among distinct risk groups. Conclusions The Lactylation-Related Gene risk model exhibits significant potential for improving the management of colorectal cancer patients and enhancing therapeutic outcomes, particularly at the intersection of metabolism and immune evasion. This finding underscores the clinical relevance of global lactylation in CRC and lays the groundwork for mechanism investigation and targeted therapeutic strategies given the high lactate concentration in CRC.

Colorectal cancer liver metastasis (CRLM) is one of the leading causes of death among patients with colorectal cancer (CRC). Although immunotherapy has demonstrated encouraging outcomes in CRC, its benefits are minimal in CRLM. The complex immune landscape of the hepatic tumour microenvironment is essential for the development of a premetastatic niche and for the colonisation and metastasis of CRC cells; thus, an in-depth understanding of these mechanisms can provide effective immunotherapeutic targets for CRLM. This review summarises recent studies on the immune landscape of the tumour microenvironment of CRLM and highlights therapeutic prospects for targeting the suppressive immune microenvironment of CRLM.

Objective Rapid on-site evaluation (ROSE) of respiratory cytology specimens is a critical technique for accurate and timely diagnosis of lung cancer. However, in China, limited familiarity with the Diff-Quik staining method and a shortage of trained cytopathologists hamper utilization of ROSE. Therefore, developing an improved deep learning model to assist clinicians in promptly and accurately evaluating Diff-Quik stained cytology samples during ROSE has important clinical value. Methods Retrospectively, 116 digital images of Diff-Quik stained cytology samples were obtained from whole slide scans. These included 6 diagnostic categories - carcinoid, normal cells, adenocarcinoma, squamous cell carcinoma, non-small cell carcinoma, and small cell carcinoma. All malignant diagnoses were confirmed by histopathology and immunohistochemistry. The test image set was presented to 3 cytopathologists from different hospitals with varying levels of experience, as well as an artificial intelligence system, as single-choice questions. Results The diagnostic accuracy of the cytopathologists correlated with their years of practice and hospital setting. The AI model demonstrated proficiency comparable to the humans. Importantly, all combinations of AI assistance and human cytopathologist increased diagnostic efficiency to varying degrees. Conclusions This deep learning model shows promising capability as an aid for on-site diagnosis of respiratory cytology samples. However, human expertise remains essential to the diagnostic process.

lncRNA can regulate tumorigenesis development and distant metastasis of colorectal cancer (CRC). However, the detailed molecular mechanisms are still largely unknown. Using RNA-sequencing data, RT-qPCR, and FISH assay, we found that HIF1A-AS2 was upregulated in CRC tissues and associated with poor prognosis. Functional experiments were performed to determine the roles of HIF1A-AS2 in tumor progression and we found that HIF1A-AS2 can promote the proliferation, metastasis, and aerobic glycolysis of CRC cells. Mechanistically, HIF1A-AS2 can promote FOXC1 expression by sponging miR-141-3p. SP1 can transcriptionally activate HIF1A-AS2. Further, HIF1A-AS2 can be packaged into exosomes and promote the malignant phenotype of recipient tumor cells. Taken together, we discovered that SP1-induced HIF1A-AS2 can promote the metabolic reprogramming and progression of CRC via miR-141-3p/FOXC1 axis. HIF1A-AS2 is a promising diagnostic marker and treatment target in CRC.

Background Ferroptosis and disulfidptosis are newly discovered forms of regulated cell death that play critical roles in cancer progression, metabolism, and immune evasion. However, their interplay and combined influence on colorectal cancer (CRC) progression remain insufficiently understood. Methods We developed a ferroptosis-disulfidptosis-related gene (FDRG) score using machine-learning algorithms to analyze gene modifications associated with these pathways in CRC, utilizing data from the TCGA and GEO databases. The model was externally validated, and associations with clinical outcomes, immune infiltration, mutational landscapes, immunotherapy responses, and drug sensitivity were explored. Key genes were further investigated through bioinformatics and in vitro experiments. Results We constructed an 8-gene risk model with strong prognostic value, stratifying CRC patients into high- and low-risk groups with significant differences in clinical characteristics, immune cell infiltration, and therapeutic responses. Among these genes, CHMP6 was identified as a previously uncharacterized tumor suppressor in CRC. Beyond its inhibitory effect on tumor cell proliferation, migration, and invasion, CHMP6 was found to play a critical role in modulating anti-tumor immunity. Our findings established CHMP6 as a dual-function tumor suppressor that not only restrains tumor progression but also enhances immune-mediated tumor control. Conclusions The FDRG score is a robust tool for predicting CRC prognosis, tumor microenvironment dynamics, and response to immunotherapy. CHMP6 emerged as a promising tumor suppressor and potential therapeutic target, offering new insights into CRC treatment strategies.

Evaluating and selecting appropriate contractors is critical to the success of specific construction projects in the building industry. Existing approaches for addressing this problem are unsatisfactory due to the ignorance of the multi-dimensional nature of the evaluation process and inappropriate consideration of existent risks. This study presents a DEA game cross-efficiency model with loss aversion for evaluating and selecting specific contractors. The competitiveness of the evaluation process is modeled using game theory with respect to the adoption of the cross-efficiency model. The attitude of the decision maker toward risks is tackled with the use of loss aversion, which is a phenomenon formalized in prospect theory. As a result, the proposed approach can adequately screen available contractors through prequalification and adequately consider the attitude of the decision maker toward risks, leading to effective decisions being made. An example is presented to demonstrate the applicability of the proposed model in evaluating and selecting appropriate contractors for specific construction projects. The results show that the proposed model is effective and efficient in producing a unique solution for contractor selection through appropriate modeling of the multi-dimensional contractor selection process and adequate consideration of the competition between the contractors and the attitude of the decision maker toward risks in practical situations.

Background The tumourigenesis of various cancers is influenced by epigenetic deregulation. Among 591 epigenetic regulator factors (ERFs) examined, AF9 showed significant inhibition of malignancy in colorectal cancer (CRC) based on our wound healing assays. However, the precise role of AF9 in CRC remains to be explored. Methods To investigate the function of AF9 in CRC, we utilised small interfering RNAs (siRNAs) to knock down the expression of 591 ERFs. Subsequently, we performed wound healing assays to evaluate cell proliferation and migration. In vitro and in vivo assays were conducted to elucidate the potential impact of AF9 in CRC. Clinical samples were analysed to assess the association between AF9 expression and CRC prognosis. Additionally, an Azoxymethane‐Dextran Sodium Sulfate (AOM/DSS) induced CRC AF9IEC‐/‐ mouse model was employed to confirm the role of AF9 in CRC. To identify the target gene of AF9, RNA‐seq and coimmunoprecipitation analyses were performed. Furthermore, bioinformatics prediction was applied to identify potential miRNAs that target AF9. Results Among the 591 ERFs examined, AF9 exhibited downregulation in CRC and showed a positive correlation with prolonged survival in CRC patients. In vitro and in vivo assays proved that depletion of AF9 could promote cell proliferation, migration as well as glycolysis. Specifically, knockout of MLLT3 (AF9) in intestinal epithelial cells significantly increased tumour formation induced by AOM/DSS. We also identified miR‐145 could target 3′untranslated region of AF9 to suppress AF9 expression. Loss of AF9 led to decreased expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase 2 (PCK2) and fructose 1,6‐bisphosphatase 1 (FBP1), subsequently promoting glucose consumption and tumourigenesis. Conclusions AF9 is essential for the upregulation of PCK2 and FBP1, and the disruption of the miR‐145/AF9 axis may serve as a potential target for the development of CRC therapeutics. 1. AF9 depletion facilitated colorectal cancer progression. 2. The miR‐145/AF9 axis holds promise as a potential therapeutic target. 3. AF9 modulated glycolysis by modifying the expression of phosphoenolpyruvate carboxykinase 2 (PCK2) and fructose 1,6‐bisphosphatase 1 (FBP1). 4. AF9 interacts with PCK2 and FBP1 through its recognition of H3K9ac.

The purpose of this study was to evaluate the risk and prognostic factors of stage IVB cervical cancer with brain metastasis from a population-based database, the Surveillance, Epidemiology and End Results (SEER). Cervical cancer patients initially diagnosed with brain metastasis between 2010 and 2019 were included in this study. The risk factors of developing brain metastasis were evaluated by logistic regression model with corresponding 95% confidence interval (95% CI). Survival analysis was performed through the Kaplan-Meier method, log-rank test, and Cox proportional hazards model. A total of 88 (88/25,476, 0.35%) cervical cancer patients initially diagnosed with brain metastasis between 2010 and 2019 were retrieved. Accompanied with lung, bone, or liver metastasis (all < 0.001) was shown to be independent risk factors for developing brain metastasis. Patients with brain metastasis indicated a poor prognosis ( < 0.001, hazards ratio [HR] = 2.84, 95% CI = 1.71-4.72) with a 2.84-fold elevated risk of death compared with patients without brain metastasis. The median survival month for patients with brain metastasis was 6 months, which is much shorter compared with the lung (9 months) or liver (8.5 months) or bone (11 months) metastasis group. Along with lower tumor grade ( = 0.001, HR = 0.27, 95% CI = 0.09-0.76) and with bone metastasis ( = 0.007, HR = 2.74, 95% CI = 1.33-5.67) demonstrated poor overall survival outcomes in patients with brain metastasis, with a 3.7- and 1.33-fold higher risk of death, respectively. In terms of treatment modality, chemoradiotherapy tended to prolong the survival of stage IVB cervical cancer patients with brain metastasis ( = 0.001, HR = 0.17, 95% CI = 0.06-0.48), with an 83% reduction in the risk of death. In conclusion, the prognosis of stage IVB cervical cancer patients with brain metastasis remains poor. Chemoradiotherapy may provide survival benefits, which deserves large-scale prospective clinical trials to confirm.

The hypoxic tumor microenvironment and long noncoding RNAs (lncRNAs) are pivotal in cancer progression and correlate with the survival outcome of patients. However, the role of hypoxia-related lncRNAs (HRLs) in colorectal cancer (CRC) development remains largely unknown. Herein, we developed a hypoxia-related lncRNA signature to predict patients’ survival and immune infiltration. The RNA-sequencing data of 500 CRC patients were obtained from The Cancer Genome Atlas (TCGA) dataset, and HRLs were selected using Pearson’s analysis. Next, the Cox regression analysis was applied to construct a risk signature consisting of 9 HRLs. This signature could predict the overall survival (OS) of CRC patients with high accuracy in training, validation, and entire cohort. This signature was an independent risk factor and exerted predictive ability in different subgroups. Functional analysis revealed different molecular features between high- and low-risk groups. A series of drugs including cisplatin showed different sensitivities between the two groups. The expression pattern of immune checkpoints was also distinct between the two clusters in this model. Furthermore, the high-risk group had higher immune, stromal, and ESTIMATE score and a more repressive immune microenvironment than the low-risk group. Moreover, MYOSLID, one of the lncRNAs in this signature, could significantly regulate the proliferation, invasion, and metastasis of CRC.