Survival Rate Of Colorectal Cancer Patients Research Articles

UBXN11 Predicts as a Poor Index for Colorectal Cancer and Contributes to the Tumorigenesis by Activating NF-κB Signaling.

The complex mechanisms of colorectal cancer (CRC) pathogenesis and progression remain poorly understood. This study endeavors to unravel the role of UBXN11within the context of CRC. UBXN11 expression level in CRC, stomach adenocarcinoma and esophageal carcinoma, and the overall survival in corresponding cancers were analyzed using UALCAN database. Human CRC cell lines and xenograft mouse model with UBXN11 overexpression were established to investigate the pathological role of UBXN11 in CRC progression. Luciferase assay, qPCR, and Western blot were performed to dissect the interaction between UBXN11 and NF-κB signaling. Heightened UBXN11 expression was observed in various digestive tract tumors, which was positively correlated with the reduced overall survival rates in CRC patients. Overexpression of UBXN11 significantly enhanced CRC cell proliferation in vitro and promoted tumor growth in vivo. Mechanistically, UBXN11 promoted CRC tumorigenesis through increasing the activation of NF-κB signaling pathway. This study underscores the pivotal role of UBXN11 in CRC progression and paves the way for novel therapeutic strategies for CRC treatment.

Abstract 3176: Otopetrin 3 promotes cell proliferation and regulates glycolysis via interaction with MYC in colorectal cancer

Abstract Otopetrin 3 (OTOP3) stands out as a pivotal regulator of intracellular pH through its control over proton transportation into cells, affecting fundamental cellular processes. Previous studies have shown that OTOP3 is associated with the prognosis of colorectal cancer (CRC) patients. However, the mechanism underlying OTOP3 regulation remains unclear in cancer. Our investigation reveals OTOP3 as a potent oncogene in CRC, with higher OTOP3 levels correlating with diminished overall survival rates in CRC patients. Comparative analysis between cancerous and normal colon cells highlights a pronounced overexpression of OTOP3 in cancer cells. Suppression of OTOP3 expression significantly curtailed CRC cell proliferation, colony formation, migration, and invasion, concurrently inducing apoptosis and cell cycle arrest, ultimately leading to cancer cell death. Moreover, through CHX, FBS inactivation, and MG132 treatment experiments, it was confirmed that OTOP3 regulates c-Myc expression and stability through ubiquitination and has a critical impact on CRC cell proliferation and growth. Additionally, OTOP3's modulation of HK2, PKM2, and LDHA, underscores its role in impacting cancer cell behavior via glycolytic pathways. In summary, the overexpression of OTOP3 in CRC cells drives cell proliferation and growth through the regulation of c-Myc, impacting crucial cellular processes. Additionally, it promotes these processes by influencing glycolysis. These findings provide valuable insights into potential therapeutic targets for CRC treatment, possibly involving OTOP3 and its associated pathways. Citation Format: Hyeung-Jin Jang, Wona Jee, So-Mi Park, Ye-rin Park, Seok Woo Kim, Ji Hoon Jung. Otopetrin 3 promotes cell proliferation and regulates glycolysis via interaction with MYC in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3176.

Evaluation and Application of Frailty Index in Colorectal Cancer: A Comprehensive Review.

Colorectal cancer (CRC) is a common malignant tumor that primarily affects the elderly population. Surgery is one of the main treatment modalities for CRC. Frailty is a prevalent characteristic among the elderly and a leading cause of mortality. The frailty index (FI) is a comprehensive tool for assessing patients' frailty status, quantifying indicators such as weight loss, fatigue, and nutritional status, to reflect the degree of frailty. In recent years, the FI has undergone modifications to more accurately evaluate the risk of surgical complications and prognosis in CRC patients. This review summarizes the methods for frailty assessment, the development and modifications of the FI, and compiles the research findings and applications of the FI in predicting surgical complications, postoperative recovery, and survival rates in CRC patients. Furthermore, limitations in the current modified frailty index (mFI) and future research directions are discussed. This review provides essential references for further understanding the role of frailty in CRC patients and the clinical application of the mFI.

Effects of T2DM on postoperative outcome of patients with colorectal cancer: a study on the relationship between blood glucose control and survival rate.

To investigate the impact of type 2 diabetes (T2DM) on the prognosis of colorectal cancer (CRC). The data of 312 patients with CRC treated in the First Affiliated Hospital of Huzhou University from 2012 to 2018 were analyzed retrospectively. The patients were divided into a comorbidity group (n = 62) and a non-comorbidity group (n = 250) according to the presence of T2DM. The baseline data of the two groups were balanced by 1:2 propensity score matching (PSM). Kaplan-Meier analysis and Log-rank test were employed to compare the 5-year overall survival (OS) rates of patients. Cox regression model and inverse probability of treatment weighting (IPTW) were utilized to assess the influence of T2DM on 5-year OS of patients. Based on the results of Cox regression, a nomogram model of T2DM on 5-year OS of patients was constructed. A total of 62 patients in the comorbidity group and 124 patients in the non-comorbidity group were matched using PSM. The 5-year OS rate was lower in the comorbidity group than in the non-comorbidity group (82.23% VS 90.32%, P = 0.038). Subgroup analysis showed that the 5-year overall survival rate was higher in the good blood glucose control group than in the poor blood glucose control group (97.14% VS 62.96%, P<0.01). Multivariate Cox regression showed that the 5-year mortality risk in the comorbidity group was 2.641 times higher than that in the non-comorbidity group (P = 0.026). IPTW analysis showed that the 5-year risk of death in the comorbidity group was 2.458 times that of the non-comorbidity group (P = 0.019). The results showed that poor blood glucose control, BMI≥25 kg/m2, low differentiation, III/IV stage, and postoperative infection were independent factors affecting the 5-year overall survival rate of CRC patients (P<0.05). The ROC curve showed that the AUCs of the constructed model in predicting the 5-year OS in the training set and the testing set were 0.784 and 0.776, respectively. T2DM is identified as a risk factor for reduced 5-year survival among CRC patients, necessitating increased attention for this subgroup, particularly those with poor blood glucose control.

XAF1 promotes colorectal cancer metastasis via VCP-RNF114-JUP axis.

Metastasis is the main cause of colorectal cancer (CRC)-related death, and the 5-year relative survival rate for CRC patients with distant metastasis is only 14%. X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a zinc-rich protein belonging to the interferon (IFN)-induced gene family. Here, we report a metastasis-promoting role of XAF1 in CRC by acting as a novel adaptor of valosin-containing protein (VCP). XAF1 facilitates VCP-mediated deubiquitination of the E3 ligase RING finger protein 114 (RNF114), which promotes K48-linked ubiquitination and subsequent degradation of junction plakoglobin (JUP). The XAF1-VCP-RNF114-JUP axis is critical for the migration and metastasis of CRC cells. Moreover, we observe correlations between the protein levels of XAF1, RNF114, and JUP in clinical samples. Collectively, our findings reveal an oncogenic function of XAF1 in mCRC and suggest that the XAF1-VCP-RNF114-JUP axis is a potential therapeutic target for CRC treatment.

Correlation between pre-treatment serum total blood bilirubin and unconjugated bilirubin and prognosis in patients with colorectal cancer.

Epidemiological studies have found that unconjugated bilirubin (UCB) levels are positively correlated with the incidence of colorectal cancer (CRC). Therefore, bilirubin may also play an important role in the prognosis of CRC. To investigate the predictive value of total bilirubin (TBIL) and UCB in the prognosis of patients with CRC. A total of 142 CRC patients were selected as the research subjects in Jingxian Hospital, from October 2014 to May 2021. General and tumour-related clinical data at admission and the overall survival at 3 years after surgery were collected. The optimal cut-off values of TBIL and UCB were determined by receiver operating characteristic curve analysis. Univariate and multivariate Cox regression were used to analyse the effect of bilirubin level on the survival of CRC patients. The Kaplan-Meier method was used to assess the survival time. The 3-year overall survival rate of CRC patients was significantly higher in the high TBIL (> 13.45 μmol/L) group than in the low TBIL (≤ 13.45 μmol/L) group (76.4% vs 37.1%; P < 0.05). The 3-year overall survival rate of CRC patients in the high UCB (> 10.75 μmol/L) group was significantly higher than that in the low UCB (≤ 10.75 μmol/L) group (83.3% vs 34.2%; P < 0.05). Multivariate Cox regression analysis showed that higher TBIL levels were an independent predictor of better prognosis in CRC patients (hazard ratio = 0.360, 95% confidence interval: 0.159-0.812, P = 0.014). TBIL levels can be used as a prognostic indicator for CRC patients.

The Advances in Chitosan-based Drug Delivery Systems for Colorectal Cancer: A Narrative Review.

Colorectal cancer (CRC) is considered a lethal cancer all around the world, and its incidence has been reported to be increasing. Chemotherapeutic drugs commonly used for treating this cancer have shown some drawbacks, including toxicity to healthy cells and non-precise delivery. Thus, there is a necessity for discovering novel diagnostic and therapeutic options to increase the survival rate of CRC patients. Chitosan, as a natural polymer, has attracted a lot attention during the past years in different fields, including cancer. Studies have indicated that chitosan-based materials play various roles in prevention, diagnosis, and treatment of cancers. Chitosan nanoparticles (NPs) have been shown to serve as anti-cancer agents, which provide sustained drug release and targeted delivery of drugs to the tumor site. In this paper, we review available literature on the roles of chitosan in CRC. We discuss the applications of chitosan in designing drug delivery systems as well as anti-cancer activities of chitosan and involved signaling pathways.

Identification of autophagy and angiogenesis modulators in colorectal cancer based on bioinformatics analysis

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-related death worldwide. The purpose of this study was to discover novel molecular pathways and potential prognosis biomarkers. To achieve this, we acquired five microarray datasets from the Gene Expression Omnibus (GEO) database. We identified differentially expressed genes between CRC and adjacent normal tissue samples and further validated them using The Cancer Genome Atlas (TCGA) database. Using various analytical approaches, including the construction of a competing endogenous RNA (ceRNA) network, Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses, as well as survival analysis, we identified key genes and pathways associated with the diagnosis and prognosis of CRC. We obtained a total of 185 differentially expressed genes, comprising 17 lncRNAs, 30 miRNAs, and 138 mRNAs. The ceRNA network consisted of 17 lncRNAs, 25 miRNAs, and 7 mRNAs. Among the 7 mRNAs involved in the ceRNA network, SLC7A5 and KRT80 were found to be upregulated, while ADIPOQ, CCBE1, KCNB1, CADM2, and CHRDL1 were downregulated in CRC. Further analysis revealed that ADIPOQ and SLC7A5 are involved in the AMPK and mTOR signaling pathway, respectively. In addition, survival analysis demonstrated a statistically significant relationship between ADIPOQ, SLC7A5, and overall survival rates in CRC patients. In conclusion, our findings suggest that downregulation of ADIPOQ and upregulation of SLC7A5 in tumor cells lead to increased mTORC1 activity, reduced autophagy, enhanced angiogenesis, and ultimately contribute to cancer progression and decreased survival in CRC patients.

Identification of CD147-positive extracellular vesicles as novel non-invasive biomarkers for the diagnosis and prognosis of colorectal cancer

BackgroundThe mortality rate of colorectal cancer (CRC) can be decreased with effective screening and early diagnosis. Exosomes are released from cancer cells into the bloodstream, and circulating exosomes may serve as novel biomarkers. This study aimed to identify a sensitive and rapid method of exosome collection and measurement using specific antibodies. MethodsExoCounter, a high-sensitive exosome-counting system, allows the identification of exosomes without enrichment or purification, based on the identification of the transmembrane protein—CD147—on serum exosomes that are associated with CRC. ResultsReceiver operating characteristic curves between healthy donors and CRC patients were described and assessed by CD147-specific exosomes (exo-CD147), CEA, and CA19-9. And area under curves for exo-CD147, CEA, and CA19-9 were 0.827 (95%CI: 0.764–0.891), 0.630 (95%CI: 0.536–0.724), and 0.659 (95%CI: 0.559–0.759), respectively. Drawing a clinical decision curve of exo-CD147 for the diagnosis of CRC metastases showed that when the threshold probability of exo-CD147 was between 20% and 92%, the net clinical utilization rate was higher than for all patients with or without metastases. A nomogram was constructed using multivariate COX regression analysis to select significant variables such as the high CD147 group (>34 × 105 particles). Calibration curves for 1-, 3-, and 5-year survival rates of CRC patients showed that the actual 1-, 3-, and 5-year survival rates were in excellent agreement with the survival rates predicted by the nomogram. ConclusionsThe increased CD147 expression in exosomes could serve as a diagnostic and prognostic biomarker for CRC.

An immune-related gene prognostic index for predicting prognosis in patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common solid malignant burdens worldwide. Cancer immunology and immunotherapy have become fundamental areas in CRC research and treatment. Currently, the method of generating Immune-Related Gene Prognostic Indices (IRGPIs) has been found to predict patient prognosis as an immune-related prognostic biomarker in a variety of tumors. However, their role in patients with CRC remains mostly unknown. Therefore, we aimed to establish an IRGPI for prognosis evaluation in CRC. RNA-sequencing data and clinical information of CRC patients were retrieved from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) databases as training and validation sets, respectively. Immune-related gene data was obtained from the ImmPort and InnateDB databases. The weighted gene co-expression network analysis (WGCNA) was used to identify hub immune-related genes. An IRGPI was then constructed using Cox regression methods. Based on the median risk score of IRGPI, patients could be divided into high-risk and low-risk groups. To further investigate the immunologic differences, Gene set variation analysis (GSVA) studies were conducted. In addition, immune cell infiltration and related functional analysis were used to identify the differential immune cell subsets and related functional pathways. We identified 49 immune-related genes associated with the prognosis of CRC, 17 of which were selected for an IRGPI. The IRGPI model significantly differentiates the survival rates of CRC patients in the different groups. The IRGPI as an independent prognostic factor significantly correlates with clinico-pathological factors such as age and tumor stage. Furthermore, we developed a nomogram to improve the clinical utility of the IRGPI score. Immuno-correlation analysis in different IRGPI groups revealed distinct immune cell infiltration (CD4+ T cells resting memory) and associated pathways (macrophages, Type I IFNs responses, iDCs.), providing new insights into the tumor microenvironment. At last, drug sensitivity analysis revealed that the high-risk IRGPI group was sensitive to 11 and resistant to 15 drugs. Our study established a promising immune-related risk model for predicting survival in CRC patients. This could help to better understand the correlation between immunity and the prognosis of CRC providing a new perspective for personalized treatment of CRC.

Therapeutic m6A Eraser ALKBH5 mRNA-Loaded Exosome-Liposome Hybrid Nanoparticles Inhibit Progression of Colorectal Cancer in Preclinical Tumor Models.

Although therapeutic targets have been developed for colorectal cancer (CRC) therapy, the therapeutic effects are not ideal and the survival rate for CRC patients remains poor. Therefore, it is crucial to recognize a specific target and develop an efficacious delivery system for CRC therapy. Herein, we demonstrate that reduced ALKBH5 mediates aberrant m6A modification and tumor progression in CRC. Mechanically, histone deacetylase 2-mediated H3K27 deacetylation inhibits ALKBH5 transcription in CRC, whereas ectopic ALKBH5 expression decreases tumorigenesis of CRC cells and protects mice from colitis-associated tumor development. Further, METTL14/ALKBH5/IGF2BPs combine to modulate JMJD8 stability in an m6A-dependent manner, which increases glycolysis and accelerates the development of CRC by enhancing the enzymatic activity of PKM2. Moreover, ALKBH5 mRNA-loaded folic acid-modified exosome-liposome hybrid nanoparticles were synthesized and significantly inhibit the progression of CRC in preclinical tumor models by modulating the ALKBH5/JMJD8/PKM2 axis and inhibiting glycolysis. Overall, our research confirms the crucial function of ALKBH5 in regulating the m6A status in CRC and provides a direct preclinical approach for using ALKBH5 mRNA nanotherapeutics for CRC.

Abstract 3380: Use of liquid biopsy for detection of pathogenic variants in cell-free tumor DNA from patients with precursor lesions and colorectal cancer

Abstract Background: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. The development of colorectal cancer is composed of multiple stages, starting with benign polyps in the large intestine and rectum, and gradually progress to carcinomas, providing a window of opportunity for early detection. Early diagnosis increases the survival rate of patients, thus making screening tests for precursor lesions (PL) and early-stage CRC essential for reducing the mortality rate. In this context, the early detection of tumors based on liquid biopsy could provide benefits for improving the survival rate of CRC patients and has emerged as a promising avenue for cancer screening. The aim of the study was to evaluate the presence of variants in plasma cell-free tumor DNA from patients with PL and CCR to identify diagnostic and early screening biomarkers. Material and Methods: The cell-free DNA (cfDNA) samples were obtained from plasma of patients that underwent diagnostic colonoscopy. Eight patients did not have any significant lesions (normal colonoscopy or hyperplastic polyp) and were classified as normal (N), 28 as CRC and 23 as PL - 13 as early adenomas (EA), 9 advanced adenomas (AA), and 1 sessile serrated lesion (SSL). In addition, the genomic DNA samples from 2 FFPE tumor matched pair samples were analyzed. Analysis of variants in 14 CRC associated genes was performed using Oncomine Colon cfDNA Assay and Ion Torrent PGM/S5 sequencer. Results and discussion: All variants were classified as missense or truncating and considered as pathogenic. Forty-seven variants were detected in nine genes (TP53, PIK3CA,FBXW7, APC, BRAF, GNAS, KRAS, MAP2K1, and SMAD4). TP53 gene showed the highest number of variants, comprising 53.19% of all detected variants, followed by KRAS (10.63%) and APC (8.51%). It was possible to detect the presence of at least one variant in ctDNA for 5 PL (5/23 - 21.73%) patients, including variants in 3 patients with early adenoma (3/13 - 23.07%) and 2 with advanced adenomas (2/9 - 22.22%) and fourteen CRC (14/28 - 50%). No variants were detected in patients with normal findings during colonoscopy. Concordance between detected variants in tumor tissue and plasma ctDNA (from matched samples) was observed only for two variants for CRC patients (GNAS and KRAS). Conclusion: The detection of variants in liquid biopsy demonstrates the potential for non-invasive early screening and diagnostic of CRC. Citation Format: Mariana Bisarro Dos Reis, Wellington dos Santos, Ana Carolina de Carvalho, Adhara Brandão, Adhara Brandão, Marcus Matsushita, Rui Manuel Reis, Denise Peixoto Guimarães. Use of liquid biopsy for detection of pathogenic variants in cell-free tumor DNA from patients with precursor lesions and colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3380.

CCAT 1- A Pivotal Oncogenic Long Non-Coding RNA in Colorectal Cancer.

Colorectal cancer (CRC) is ranked as the third most common cancer and second deadliest cancer in both men and women in the world. Currently, the cure rate and 5-year survival rate of CRC patients remain relatively low. Therefore, discovering a novel molecular biomarker that can be used to improve CRC screening, diagnosis, prognosis, and treatment would be beneficial. Long non-coding RNA colon cancer-associated transcript 1 (CCAT 1) has been found overexpressed in CRC and is associated with CRC tumorigenesis and treatment outcome. CCAT 1 has a high degree of specificity and sensitivity, it is readily detected in CRC tissues and is significantly overexpressed in both premalignant and malignant CRC tissues. Besides, CCAT 1 is associated with clinical manifestation and advanced features of CRC, such as lymph node metastasis, high tumor node metastasis stage, differentiation, invasion, and distant metastasis. In addition, they can upregulate oncogenic c-MYC and negatively modulate microRNAs via different mechanisms of action. Furthermore, dysregulated CCAT 1 also enhances the chemoresistance in CRC cells while downregulation of them reverses the malignant phenotypes of cancer cells. In brief, CCAT 1 serves as a potential screening, diagnostic and prognostic biomarker in CRC, it also serves as a potential therapeutic marker to treat CRC patients.

High expression of LY6E is an independent prognostic factor of colorectal cancer patients.

Colorectal cancer (CRC) is common cancer worldwide, and the 5‑year relative survival rate of CRC patients with distant metastasis is as low as 14%. Therefore, identifying markers of CRC is important for the early detection of CRC and applying appropriate treatment strategies. The lymphocyte antigen 6 family (LY6 family) is closely related to the behavior of various cancer types. Among the LY6 family, the lymphocyte antigen 6 complex, locus E (LY6E), which is specifically highly expressed in CRC. Hence, the effects of LY6E on cell function in CRC and its role in CRC recurrence and metastasis were investigated. Reverse transcription‑quantitative PCR, western blotting and invitro functional studies were carried out using four CRC cell lines. Immunohistochemical analysis of 110 CRC tissues was performed to explore the biological functions and expression patterns of LY6E in CRC. LY6E was overexpressed CRC tissues compared with that in adjacent normal tissues. High expression of LY6E in CRC tissues was an independent prognostic factor of worse overall survival (P=0.048). Knockdown of LY6E using small interfering RNA inhibited CRC cell proliferation, migration, invasion, and soft agar colony formation, indicating some of its effects on CRC carcinogenic functions. High expression of LY6E may have oncogenic functions in CRC and be useful as a valuable prognostic marker and potential therapeutic target for CRC.

Circ_0084188 Regulates the progression of colorectal cancer through the miR-769-5p/KIF20A axis.

Colorectal cancer (CRC) is one of the major gastrointestinal malignancies threatening human health. More and more studies indicate that circular RNAs (circRNAs) are important regulatory factors of CRC, but the mechanism is still indistinct. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of circ_0084188, microRNA-769-5p (miR-769-5p), and kinesin family member 20A (KIF20A) in CRC tissues. Kaplan-Meier curve was used to analyze the relationship between circ_0084188 expression and the survival rate of CRC patients. Cell proliferation, viability, apoptosis, migration, and invasion were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound-healing, and transwell assays, respectively. The relationship between miR-769-5p and circ_0084188 or KIF20A was detected by a dual-luciferase reporter and RNA pull-down. The effect of circ_0084188 on tumor growth was verified by xenograft studies in vivo. Circ_0084188 and KIF20A were upregulated and miR-769-5p was downregulated in CRC. Circ_0084188 knockdown repressed the proliferation, migration, and invasion of CRC cells, as well as enhanced apoptosis in vitro. Mechanistically, circ_0084188 targeted miR-769-5p, and the reduction of miR-769-5p reversed the effects of circ_0084188 knockdown on cell functional behaviors. KLF20A was a direct miR-769-5p target, and circ_0084188 acted as a sponge for miR-769-5p to regulate the KIF20A level. Moreover, miR-769-5p regulated the functional behaviors of CRC cells by targeting KIF20A. In addition, circ_0084188 knockdown confined the growth of xenograft tumors in vivo. Circ_0084188 upregulated the expression of KIF20A to promote the tumorigenesis of CRC through miR-769-5p, providing a new therapeutic target for CRC.

Identification of potential biomarkers for colorectal cancer by clinical database analysis and Kaplan-Meier curves analysis.

This study aimed to explore critical genes as potential biomarkers for the diagnosis and prognosis of colorectal cancer (CRC) for clinical utility. To identify and screen candidate genes involved in CRC carcinogenesis and disease progression, we downloaded microarray datasets GSE89076, GSE73360, and GSE32323 from the GEO database identified differentially expressed genes (DEGs), and performed a functional enrichment analysis. A protein-protein interaction network was constructed, and correlated module analysis was performed using STRING and Cytoscape. The Kaplan-Meier survival curve shows the survival of the hub genes. The expression of cyclin-dependent kinase (CDK1), cyclin B1 (CCNB1), and PCNA in tissues and changes in tumor grade were analyzed. A total of 329 DEGs were identified, including 264 upregulated and 65 downregulated genes. The functions and pathways of DEGs include the mitotic cell cycle, poly(A) RNA binding replication, ATP binding, DNA replication, ribosome biogenesis in eukaryotes, and RNA transport. Forty-seven Hub genes were identified, and biological process analysis showed that these genes were mainly enriched in cell cycle and DNA replication. Patients with mutations in CDK1, PCNA, and CCNB1 had poorer survival rates. CDK1, PCNA, and CCNB1 were significantly overexpressed in the tumor tissues. The expression of CDK1 and CCNB1 gradually decreased with increasing tumor grade. CDK1, CCNB1, and PCNA can be used as potential markers for the diagnosis and prognosis of CRC. These genes are overexpressed in colon cancer tissues and are associated with low survival rates in CRC patients.

Using an anomaly detection approach for the segmentation of colorectal cancer tumors in whole slide images

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in the United States. Genetic testing is critical in assisting in the early detection of CRC and selection of individualized treatment plans, which have shown to improve the survival rate of CRC patients. The tissue slide review (TSR), a tumor tissue macro-dissection procedure, is a required pre-analytical step to perform genetic testing. Due to the subjective nature of the process, major discrepancies in CRC diagnostics by pathologists are reported, and metrics for quality are often only qualitative. Progressive context encoder anomaly detection (P-CEAD) is an anomaly detection approach to detect tumor tissue from whole slide images (WSIs), since tumor tissue is by its nature, an anomaly. P-CEAD-based CRC tumor segmentation achieves a 71% 26% sensitivity, 92% 7% specificity, and 63% 23% F1 score. The proposed approach provides an automated CRC tumor segmentation pipeline with a quantitatively reproducible quality compared with the conventional manual tumor segmentation procedure.

A novel Anoikis and immune-related genes marked prognostic signature for colorectal cancer.

Colorectal cancer (CRC) is second most commonly diagnosed cancer with high morbidity and mortality. The heterogeneity of CRC makes clinical treatment tremendously challenging. Here, we aimed to comprehensively analyze the prognosis of CRC patients based on ANOIKIS- and immune-related genes. ANOIKIS-related genes were identified by differentially analysis of high anoikis score group (ANOIKIS_high group) and low anoikis score group (ANOIKIS_low group) divided by the cutoff value of anoikis score. Immune-related genes were screened by differentially analysis of high immune score group (ImmuneScore_high group) and low immune score group (ImmuneScore_low group) classified by the cutoff value of ImmuneScore. Prognostic ANOIKIS- and immune-related genes were identified by univariate Cox regression analysis. Multivariate Cox regression analysis were used for prognostic model construction. Ferroptosis expression profiles, the infiltration of immune cells, and the somatic mutation status were analyzed and compared. Univariate and multivariate Cox-regression analyses were performed to identify independent prognostic factors for CRC patient. Nomogram that contained the independent prognostic factors was established to predict 1-, 3-, and 5-year OS probability of CRC patients. Three ANOIKIS- and immune-related signatures were applied to construct a prognostic model, which divided the CRC patients into high-risk and low-risk groups. The patients with high-risk scores had obviously shorter OSs than those with low-risk scores. The time dependent ROC curve indicated that the risk score model had a stable performance to predict survival rates. Notably, the age, pathologic T, and risk score could be used independent indicators for CRC prognosis prediction. A nomogram containing the independent prognostic factors showed that the nomogram accurately predicted 1-, 3-, and 5-year survival rates of CRC patients. In our research, a novel prognostic model was developed based on ANOIKIS- and immune-related genes in CRC, which could be used for prognostic prediction of CRC patients.

TRPM8 indicates poor prognosis in colorectal cancer patients and its pharmacological targeting reduces tumour growth in mice by inhibiting Wnt/β-catenin signalling.

Transient receptor potential melastatin type-8 (TRPM8) is a cold-sensitive cation channel protein belonging to the TRP superfamily of ion channels. Here, we reveal the molecular mechanism of TRPM8 and its clinical relevance in colorectal cancer (CRC). TRPM8 expression and its correlation with the survival rate of CRC patients was analysed. To identify the key pathways and genes related to TRPM8 high expression, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted in CRC patients. TRPM8 functional role was assessed by using Trpm8-/- mice in models of sporadic and colitis-associated colon cancer. TRPM8 pharmacological targeting by WS12 was evaluated in murine models of CRC. TRPM8 is overexpressed in colon primary tumours and in CD326+ tumour cell fraction. TRPM8 high expression was related to lower survival rate of CRC patients, Wnt-Frizzled signalling hyperactivation and adenomatous polyposis coli down-regulation. In sporadic and colitis-associated models of colon cancer, either absence or pharmacological desensitization of TRPM8 reduced tumour development via inhibition of the oncogenic Wnt/β-catenin signalling. TRPM8 pharmacological blockade reduced tumour growth in CRC xenograft mice by reducing the transcription of Wnt signalling regulators and the activation of β-catenin and its target oncogenes such as C-Myc and Cyclin D1. Human data provide valuable insights to propose TRPM8 as a prognostic marker with a negative predictive value for CRC patient survival. Animal experiments demonstrate TRPM8 involvement in colon cancer pathophysiology and its potential as a drug target for CRC.

Bioinformatics-based identification of key genes and pathways associated with colorectal cancer diagnosis, treatment, and prognosis.

Colorectal cancer (CRC) is known to display a high risk of metastasis and recurrence. The main objective of our investigation was to shed more light on CRC pathogenesis by screening CRC datasets for the identification of key genes and signaling pathways, possibly leading to new approaches for the diagnosis and treatment of CRC. We downloaded the colorectal cancer datasets from the Gene Expression Omnibus (GEO) database site. We used GEO2R to screen for differentially expressed genes (DEGs) of which those with a fold change >1 were considered as up-regulated and those with a fold change <-1 were considered as down-regulated on the basis of a P < .05. “Gene ontology (GO)” and “Kyoto Encyclopedia of Genes and Genomes (KEGG)” data were analyzed by the “DAVID” software. The online search tool “STRING” was used to search for interacting genes or proteins and we used Cytoscape (v3.8.0) to generate a PPI network map and to identify key genes. Finally, survival analysis and stage mapping of key genes were performed using “GEPIA” with the aim of elucidating their potential impact on CRC. Our study revealed 120 intersecting genes of which 55 were up- and 65 were downregulated, respectively. GO analysis revealed that these genes were involved in cell proliferation, exosome secretion, G2/M transition, cytosol, protein binding, and protein kinase activity. KEGG pathway analysis showed that these genes were involved in cell cycle and mineral absorption. The Cytoscape PPI map showed 17 nodes and 262 edges, and 10 hub genes were identified by top 10 degrees. Survival analysis demonstrated that the AURKA, CCNB1, and CCNA2 genes were strongly associated with the survival rate of CRC patients. In addition, CCNB1, CCNA2, CDK1, CKS2, MAD2L1, and DLGAP5 could be correlated to pathological CRC staging. In this research, we identified key genes that may explain the molecular mechanism of occurrence and progression of CRC but may also contribute to an improvement in the clinical staging and prognosis of CRC patients.