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1.
Front Immunol ; 15: 1371584, 2024.
Article En | MEDLINE | ID: mdl-38694509

Backgrounds: Extracellular matrix (ECM) is an important component of tumor microenvironment, and its abnormal expression promotes tumor formation, progression and metastasis. Methods: Weighted gene co-expression network analysis (WGCNA) was used to identify ECM-related hub genes based on The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) data. COAD clinical samples were used to verify the expression of potential biomarkers in tumor tissues, and siRNA was used to explore the role of potential biomarkers in cell proliferation and epithelial-mesenchymal transition (EMT). Results: Three potential biomarkers (LEP, NGF and PCOLCE2) related to prognosis of COAD patients were identified and used to construct ERGPI. Immunohistochemical analysis of clinical samples showed that the three potential biomarkers were highly expressed in tumor tissues of COAD patients. Knockdown of LEP, NGF or PCOLCE2 inhibited COAD cell proliferation and EMT. Dictamnine inhibited tumor cell growth by binding to these three potential biomarkers based on molecular docking and transplanted tumor model. Conclusion: The three biomarkers can provide new ideas for the diagnosis and targeted therapy of COAD patients.


Adenocarcinoma , Biomarkers, Tumor , Colonic Neoplasms , Computational Biology , Epithelial-Mesenchymal Transition , Extracellular Matrix , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colonic Neoplasms/diagnosis , Colonic Neoplasms/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Computational Biology/methods , Extracellular Matrix/metabolism , Animals , Epithelial-Mesenchymal Transition/genetics , Mice , Cell Proliferation/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Prognosis , Tumor Microenvironment , Molecular Docking Simulation , Gene Expression Profiling , Male , Gene Regulatory Networks
2.
J Am Board Fam Med ; 37(2): 328-331, 2024.
Article En | MEDLINE | ID: mdl-38740492

BACKGROUND: CRC screening is recommended for adults aged 45-75. Mt-sDNA is indicated for asymptomatic individuals between the ages of 45 and 85, but not for those with rectal bleeding, iron deficiency anemia, adenomatous polyps, previous colonoscopy within 10 years, family history of CRC, positive results from CRC screening tests within the past 6 months, or age less than 45 and greater than 85. We aimed to determine the prevalence of mt-sDNA use when not indicated and factors associated with inappropriate testing. METHODS: 7,345 patients underwent mt-sDNA testing and were randomized using EMERSE. Charts for the first 500 patients were reviewed to determine whether mt-sDNA was ordered appropriately according to the USPSTF criteria. Seven patients were excluded due to having more than one inappropriate ordering for mt-sDNA. RESULTS: Of 500 patients, 22.2% had an inappropriately ordered mt-sDNA test. The most common reason for inappropriate ordering was having a previous colonoscopy done within the past 10 years. Rates of inappropriate testing significantly varied by race and the specialty of the ordering provider, with internal medicine providers ordering the most mt-sDNA tests. Rates of inappropriate testing did not significantly vary by sex or type of insurance. DISCUSSION: Our study suggests that providers may not be familiar with guidelines for the indicated use of mtsDNA, leading to inappropriate referrals and increased costs. Patients at increased CRC risk would benefit from a more sensitive procedure such as a colonoscopy. Future studies could understand the motivation to order testing outside approved indications through provider surveys and interviews.


Early Detection of Cancer , Humans , Female , Male , Middle Aged , Aged , Early Detection of Cancer/methods , Early Detection of Cancer/statistics & numerical data , Feces/chemistry , Aged, 80 and over , Colonoscopy/statistics & numerical data , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Practice Patterns, Physicians'/statistics & numerical data , Colorectal Neoplasms/diagnosis , Mass Screening/methods , Mass Screening/statistics & numerical data , Unnecessary Procedures/statistics & numerical data
3.
BMJ Case Rep ; 17(4)2024 Apr 24.
Article En | MEDLINE | ID: mdl-38663897

A colonic lipoma is an uncommon lesion that is linked with clinical symptoms in only a small portion of patients. Patients with large lipomas are often referred for major surgery, which is associated with significant morbidity and mortality. In this case, we described a female patient with recurrent episodes of gastrointestinal blood loss, abdominal pain and colocolic intussusceptions due to a large, lumen-filling, obstructive lipoma in the splenic flexure. On abdominal CT, a lesion of 3.6 cm was visualised with a fat-like density without solid components. Considering its benign nature, we intended to preserve the colon by deroofing the upper part of the lesion and then performing a colonoscopy-assisted laparoscopic wedge resection. During reassessment, auto-amputation of part of the lesion was observed, most likely as a result of long-lasting mechanical effects, which made it possible to perform solely a wedge resection with an excellent outcome.


Colonic Neoplasms , Colonoscopy , Laparoscopy , Lipoma , Humans , Lipoma/surgery , Lipoma/diagnostic imaging , Female , Colonic Neoplasms/surgery , Colonic Neoplasms/diagnosis , Colonic Neoplasms/diagnostic imaging , Laparoscopy/methods , Colonoscopy/methods , Middle Aged , Tomography, X-Ray Computed , Abdominal Pain/etiology , Intussusception/surgery , Intussusception/diagnostic imaging , Intussusception/diagnosis , Treatment Outcome
4.
Int Immunopharmacol ; 132: 112034, 2024 May 10.
Article En | MEDLINE | ID: mdl-38588631

Colon adenocarcinoma (COAD) is a common cause of cancer-related death. Due to the difficulty in early diagnosis and drug resistance, conventional treatments are difficult to be effective. Some studies have found that the functional recovery of T cells in the tumor microenvironment, especially regulatory T cells (Tregs), plays an important role in the progression of cancer. This study used the TCGA data set, clinical information and RNA-seq data of COAD patients to construct a Tregs-related risk score (TRS) through methods such as WGCNA, single-factor Cox, multi-factor Cox and random survival forest (RSF). Moreover, we also used the TCGA test set and internal validation set to verify the predictive ability of TRS, and used functional enrichment analysis and somatic mutation analysis to mine genes related to TRS, such as like thrombin/trypsin receptor 2 (F2RL2), inhibin subunit beta B (INHBB) and melanoma antigen family A12 (MAGEA12). Moreover, this study confirmed the expression of these prognostic genes using scRNA-seq data. We also performed qPCR analysis of various genes in normal and cancerous colon cancer cell lines to verify that these genes indeed play a role in CODA patients. We also constructed a mouse CODA model to study and evaluate the impact of key genes such as MAGEA12 on tumor growth in mice. This study explores the important role of Treg cells in the prognosis of COAD and discovers some potential biomarkers for the occurrence and development of COAD, which provides some new ideas for the treatment of COAD.


Adenocarcinoma , Colonic Neoplasms , T-Lymphocytes, Regulatory , Humans , Animals , T-Lymphocytes, Regulatory/immunology , Colonic Neoplasms/genetics , Colonic Neoplasms/immunology , Colonic Neoplasms/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/immunology , Adenocarcinoma/mortality , Prognosis , Mice , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Cell Line, Tumor , Transcriptome , Male , Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , Female , Gene Expression Profiling
6.
Int Immunopharmacol ; 130: 111771, 2024 Mar 30.
Article En | MEDLINE | ID: mdl-38430807

BACKGROUND: Siglec9 has been identified as an immune checkpoint molecule on tumor-associated macrophages (TAMs). Nevertheless, the expression profile and clinical significance of Siglec9 + TAMs in colon cancer (CC) are still not fully understood. METHODS: Two clinical cohorts from distinct medical centers were retrospectively enrolled. Immunohistochemistry and immunofluorescence were conducted to evaluate the infiltration of immune cells. Single-cell RNA sequencing and flow cytometry were utilized to identify the impact of Siglec9 + TAMs on the tumor immune environment, which was subsequently validated through bioinformatics analysis of the TCGA database. Prognosis and the benefit of adjuvant chemotherapy (ACT) were also evaluated using Cox regression analysis and the Kaplan-Meier method. RESULTS: High infiltration of Siglec9 + TAMs was associated with worse prognosis and better benefit from 6-month ACT. Siglec9 + TAMs contributed to immunoevasion by promoting the infiltration of immunosuppressive cells and the dysfunction process of CD8 + T cells. Additionally, high infiltration of Siglec9 + TAMs was associated with the mesenchymal-featured subtype and overexpression of the VEGF signaling pathway, which was validated by the strongest communication between Siglec9 + TAMs and vascular endothelial cells. CONCLUSIONS: Siglec9 + TAMs may serve as a biomarker for prognosis and response to ACT in CC. Furthermore, the immunoevasive contexture and angiogenesis stimulated by Siglec9 + TAMs suggest potential treatment combinations for CC patients.


Antigens, CD , Colonic Neoplasms , Sialic Acid Binding Immunoglobulin-like Lectins , Tumor-Associated Macrophages , Humans , Colonic Neoplasms/diagnosis , Colonic Neoplasms/pathology , Endothelial Cells , Prognosis , Retrospective Studies , Tumor Microenvironment , Tumor-Associated Macrophages/immunology , Antigens, CD/metabolism , Sialic Acid Binding Immunoglobulin-like Lectins/metabolism , Male , Female , Adult , Middle Aged
7.
Front Endocrinol (Lausanne) ; 15: 1344058, 2024.
Article En | MEDLINE | ID: mdl-38501104

Background: PANoptosis is a newly discovered cell death type, and tightly associated with immune system activities. To date, the mechanism, regulation and application of PANoptosis in tumor is largely unknown. Our aim is to explore the prognostic value of PANoptosis-related genes in colon adenocarcinoma (COAD). Methods: Analyzing data from The Cancer Genome Atlas-COAD (TCGA-COAD) involving 458 COAD cases, we concentrated on five PANoptosis pathways from the Molecular Signatures Database (MSigDB) and a comprehensive set of immune-related genes. Our approach involved identifying distinct genetic COAD subtype clusters and developing a prognostic model based on these parameters. Results: The research successfully identified two genetic subtype clusters in COAD, marked by distinct profiles in PANoptosis pathways and immune-related gene expression. A prognostic model, incorporating these findings, demonstrated significant predictive power for survival outcomes, underscoring the interplay between PANoptosis and immune responses in COAD. Conclusion: This study enhances our understanding of COAD's genetic framework, emphasizing the synergy between cell death pathways and the immune system. The development of a prognostic model based on these insights offers a promising tool for personalized treatment strategies. Future research should focus on validating and refining this model in clinical settings to optimize therapeutic interventions in COAD.


Adenocarcinoma , Colonic Neoplasms , Humans , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Adenocarcinoma/genetics , Prognosis , Multigene Family , Biomarkers
8.
BMC Infect Dis ; 24(1): 293, 2024 Mar 06.
Article En | MEDLINE | ID: mdl-38448866

BACKGROUND: Colorectal cancer is one of the most frequently diagnosed forms of cancer, and it is associated with several common symptoms and signs such as rectal bleeding, altered bowel habits, abdominal pain, anemia, and unintentional weight loss. Sciatica, a debilitating condition in which the patient experiences paresthesia and pain in the dermatome of associated lumbosacral nerve roots or sciatic nerve distribution, is not considered one of these. Here we present a case of colorectal cancer manifesting symptoms of sciatica alone. CASE PRESENTATION: A 68-year-old male presented with progressive lower back pain radiating to his left thigh and calf over L5/S1 dermatome. Sciatica was suspected and initially underwent conservative treatment with analgesics. However, the symptoms progressed and MRI revealed an epidural abscess surprisingly. Surgical debridement was performed and pus culture isolated Streptococcus gallolyticus. Based on the strong association of S. gallolyticus with colorectal cancer, the presence of this pathogen prompted further tumor evaluation, even in the absence of the typical symptoms and signs. This investigation ultimately leads to the diagnosis of sigmoid adenocarcinoma. CONCLUSIONS: Although rare, sciatica caused by S. gallolyticus infection of the spinal epidural space may serve as the initial presentation of colorectal cancer. Physicians should be aware of the strong association between S. gallolyticus and colorectal cancer. Based on what we currently know about the condition; a thorough systematic assessment of occult neoplasia for patients with S. gallolyticus infection is recommended.


Colonic Neoplasms , Epidural Abscess , Sciatica , Male , Humans , Aged , Sciatica/diagnosis , Sciatica/etiology , Epidural Abscess/diagnosis , Epidural Abscess/surgery , Colonic Neoplasms/complications , Colonic Neoplasms/diagnosis , Abdominal Pain , Awareness
9.
Sci Rep ; 14(1): 2867, 2024 02 04.
Article En | MEDLINE | ID: mdl-38311637

Currently, immunotherapy has entered the clinical diagnosis and treatment guidelines for colon cancer, but existing immunotherapy markers cannot predict the effectiveness of immunotherapy well. This study utilized the TCGA-COAD queue to perform differential gene analysis on high and low-mutation burden samples, and screen differentially expressed genes (DEGs). To explore new molecular markers or predictive models of immunotherapy by using DEGs for NMF classification and prognostic model construction. Through systematic bioinformatics analysis, the TCGA-COAD cohort was successfully divided into high mutation burden subtypes and low mutation burden subtypes by NMF typing using DEGs. The proportion of MSI-H between high mutation burden subtypes was significantly higher than that of low mutation burden subtypes, but there was no significant difference in immunotherapy efficacy between the two subtypes. Drug sensitivity analysis showed significant differences in drug sensitivity between the two subtypes. Subsequently, we constructed a prognostic model using DEGs, which can effectively predict patient survival and immunotherapy outcomes. The prognosis and immunotherapy outcomes of the low-risk group were significantly better than those of the high-risk group. The external dataset validation of the constructed prognostic model using the GSE39582 dataset from the GEO database yielded consistent results. At the same time, we also analyzed the TMB and MSI situation between the high and low-risk groups, and the results showed that there was no significant difference in TMB between the high and low-risk groups, but the proportion of MSI-H in the high-risk group was significantly higher than that in the low-risk group. Finally, we conclude that TMB is not a suitable molecular marker for predicting the efficacy of immunotherapy in colon cancer. The newly constructed prognostic model can effectively differentiate the prognosis of colon cancer patients and predict their immunotherapy efficacy.


Colonic Neoplasms , Humans , Prognosis , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Colonic Neoplasms/therapy , Immunotherapy , Computational Biology , Microsatellite Instability , Mutation
10.
Eur J Cancer Prev ; 33(2): 105-114, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38299664

OBJECTIVES: Adjuvant chemotherapy benefits in elderly patients with stage II colon cancer (CC) remain controversial. We aimed to construct a nomogram to estimate the chemotherapy survival benefits in elderly patients. METHODS: The training and testing cohort were patients with stage II CC older than 70 years from the Surveillance, Epidemiology, and End Results (SEER) database, while the external validation cohort included patients from the National Cancer Center (NCC). Cox proportional hazard models were used to determine the covariates associated with overall survival (OS). Using the risk factors identified by Cox proportional hazards regression, a nomogram was developed to predict OS. Nomogram precision was assessed using receiver operating characteristic and calibration curves. RESULTS: The present study recruited 42 097 and 504 patients from the SEER database and NCC, respectively. The OS of patients who underwent surgery plus adjuvant chemotherapy was considerably longer than patients who underwent surgery alone. The nomogram included variables related to OS, including age, year of diagnosis, sex, AJCC T stage, tumor location, tumor size, harvested lymph nodes, and chemotherapy. According to the nomogram score, the elderly patients were separated into high- and low-risk groups, with high-risk group nomogram scores being greater than the median value, and vice versa. Patients in the high-risk group witnessed worse prognosis and were more likely to benefit from postoperative chemotherapy. CONCLUSION: This nomogram can be regarded as a useful clinical tool for assessing the potential adjuvant chemotherapy benefits and for predicting survival in elderly patients with stage II CC.


Colonic Neoplasms , Nomograms , Aged , Humans , Prognosis , Chemotherapy, Adjuvant , Colonic Neoplasms/diagnosis , Colonic Neoplasms/drug therapy , Colonic Neoplasms/epidemiology , Databases, Factual
11.
Can Vet J ; 65(1): 25-28, 2024 Jan.
Article En | MEDLINE | ID: mdl-38164375

An 8-year-old spayed female British bulldog was presented with vomiting, hyporexia, and large-bowel diarrhea. Abdominal ultrasound revealed a focal colonic mass with an intussusception located immediately oral to the mass. The intussusception encompassed the ascending and transverse colon and was non-reducible. Colonic resection and anastomosis were completed to include the intussusception and colonic mass. Histopathological examination of the mass demonstrated a spindle cell neoplasm arising within the muscular wall of the intussuscepted segment that obliterated normal architecture. Mild-to-moderate cytoplasmic immunoreactivity of the tumor cell population for CD117 and smooth muscle actin was consistent with a diagnosis of a gastrointestinal stromal tumor. The dog described herein remains alive and free of progressive disease at the time of writing. Key clinical message: The entire gastrointestinal tract should be evaluated in any animal with gastrointestinal symptoms. A gastrointestinal stromal tumor remains a plausible differential diagnosis, regardless of the intestinal segment affected, and tumorassociated intussusception is a rare but urgent clinical finding.


Tumeur stromale gastro-intestinale du côlon (GIST) présentant une invagination colocolique : un rapport de cas rare. Une femelle bouledogue anglais stérilisée de 8 ans a présenté des vomissements, une hyporexie et une diarrhée d'origine du gros intestin. L'échographie abdominale a révélé une masse colique focale avec une invagination située immédiatement oralement à la masse. L'intussusception englobait le côlon ascendant et transverse et était non réductible. La résection colique et l'anastomose ont été réalisées pour inclure l'intussusception et la masse colique. L'examen histopathologique de la masse a révélé un néoplasme à cellules fusiformes apparaissant dans la paroi musculaire du segment invaginé qui a oblitéré l'architecture normale. L'immunoréactivité cytoplasmique légère à modérée de la population de cellules tumorales pour le CD117 et l'actine des muscles lisses étaient compatibles avec un diagnostic de tumeur stromale gastro-intestinale. Le chien décrit ici est toujours vivant et exempt de maladie évolutive au moment de la rédaction.Message clinique clé :L'ensemble du tractus gastro-intestinal doit être évalué chez tout animal présentant des symptômes gastrointestinaux. Une tumeur stromale gastro-intestinale reste un diagnostic différentiel plausible, quel que soit le segment intestinal atteint, et l'intussusception associée à la tumeur est une constatation clinique rare mais urgente.(Traduit par Dr Serge Messier).


Colonic Neoplasms , Dog Diseases , Gastrointestinal Stromal Tumors , Intussusception , Female , Animals , Dogs , Intussusception/diagnosis , Intussusception/surgery , Intussusception/veterinary , Gastrointestinal Stromal Tumors/complications , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/veterinary , Colonic Neoplasms/complications , Colonic Neoplasms/diagnosis , Colonic Neoplasms/surgery , Colonic Neoplasms/veterinary , Diagnosis, Differential , Dog Diseases/diagnosis , Dog Diseases/surgery
12.
Histopathology ; 84(6): 1038-1046, 2024 May.
Article En | MEDLINE | ID: mdl-38253910

AIMS: Large venous invasion (VI) is prognostically significant in colon cancer. The increased use of elastic stains by pathologists results in higher VI detection rates compared to routine stains alone. This study assesses the prognostic value of VI detected by elastic versus routine stains. METHODS AND RESULTS: Colon cancers resected between 2014 and 2017 underwent pathology slide review for VI. Cases without VI on routine stain were stained by elastic trichrome and re-examined. Demographic, clinical, pathological and outcome data were gathered by retrospective review. Kaplan-Meier curves with log-rank tests were performed for survival categorised by VI status. Cox regression was performed for multivariate analysis. Of 277 cases, 97 (35%) showed VI by routine stain alone, with an additional 58 (21%) discovered by subsequent elastic stains. Thus, elastic trichrome increased VI detection by 60%. However, only VI detected by routine stain showed worse overall survival (P < 0.001). VI detected by elastic stain only was not prognostically different from cases without VI (P = 0.428). For stage 2 cancers, VI was not prognostically significant regardless of method of detection. For stage 3 cases, only VI detected by routine stain was prognostic for overall survival (P = 0.002) with a hazard ratio of 4.04 by multivariate regression (P = 0.028). CONCLUSIONS: VI detectable only by elastic stains do not show prognostic significance for survival in colon cancer. For pathologists with high baseline VI detections rates on routine stain, reflexive use of elastic stain may be of limited value.


Colonic Neoplasms , Colorectal Neoplasms , Humans , Prognosis , Coloring Agents , Colorectal Neoplasms/pathology , Neoplasm Staging , Colonic Neoplasms/diagnosis , Colonic Neoplasms/pathology , Neoplasm Invasiveness/pathology , Retrospective Studies
13.
Endoscopy ; 56(5): 376-383, 2024 May.
Article En | MEDLINE | ID: mdl-38191000

BACKGROUND: Adenoma detection rate (ADR) is an important indicator of colonoscopy quality and colorectal cancer incidence. Both linked-color imaging (LCI) with artificial intelligence (LCA) and LCI alone increase adenoma detection during colonoscopy, although it remains unclear whether one modality is superior. This study compared ADR between LCA and LCI alone, including according to endoscopists' experience (experts and trainees) and polyp size. METHODS: Patients undergoing colonoscopy for positive fecal immunochemical tests, follow-up of colon polyps, and abdominal symptoms at a single institution were randomly assigned to the LCA or LCI group. ADR, adenoma per colonoscopy (APC), cecal intubation time, withdrawal time, number of adenomas per location, and adenoma size were compared. RESULTS: The LCA (n=400) and LCI (n=400) groups showed comparable cecal intubation and withdrawal times. The LCA group showed a significantly higher ADR (58.8% vs. 43.5%; P<0.001) and mean (95%CI) APC (1.31 [1.15 to 1.47] vs. 0.94 [0.80 to 1.07]; P<0.001), particularly in the ascending colon (0.30 [0.24 to 0.36] vs. 0.20 [0.15 to 0.25]; P=0.02). Total number of nonpolypoid-type adenomas was also significantly higher in the LCA group (0.15 [0.09 to 0.20] vs. 0.08 [0.05 to 0.10]; P=0.02). Small polyps (≤5, 6-9mm) were detected significantly more frequently in the LCA group (0.75 [0.64 to 0.86] vs. 0.48 [0.40 to 0.57], P<0.001 and 0.34 [0.26 to 0.41] vs. 0.24 [0.18 to 0.29], P=0.04, respectively). In both groups, ADR was not significantly different between experts and trainees. CONCLUSIONS: LCA was significantly superior to LCI alone in terms of ADR.


Adenoma , Artificial Intelligence , Colonic Polyps , Colonoscopy , Adult , Aged , Female , Humans , Male , Middle Aged , Adenoma/diagnosis , Adenoma/diagnostic imaging , Colonic Neoplasms/diagnosis , Colonic Neoplasms/diagnostic imaging , Colonic Polyps/diagnosis , Colonic Polyps/diagnostic imaging , Colonoscopy/methods , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/diagnostic imaging
14.
Clin Lab ; 70(1)2024 Jan 01.
Article En | MEDLINE | ID: mdl-38213210

BACKGROUND: In this case study, the patient first had a colonoscopy based on an incidental episode of vomiting and abdominal pain. MATERIALS AND METHODS: Two months after recovery, a multitarget stool test (ColoAlert®) was performed and showed a known somatic mutation in the oncogene KRAS, reported to be associated with colorectal cancer. As a result, a second complete colonoscopy was performed at another center. RESULTS: This procedure led to the diagnosis and removal of a later classified high-risk polyp that had been missed during the initial colonoscopy. CONCLUSIONS: This case report shows the use of genetic markers in stool testing has the potential to detect colon cancer in very early stages when treatment is inexpensive and effective.


Colonic Neoplasms , Colorectal Neoplasms , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Genetic Markers , Colonoscopy/methods , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Early Detection of Cancer/methods , Feces
15.
Sci Rep ; 14(1): 622, 2024 01 05.
Article En | MEDLINE | ID: mdl-38182713

Lysosomes are essential components for managing tumor microenvironment and regulating tumor growth. Moreover, recent studies have also demonstrated that long non-coding RNAs could be used as a clinical biomarker for diagnosis and treatment of colorectal cancer. However, the influence of lysosome-related lncRNA (LRLs) on the progression of colon cancer is still unclear. This study aimed to identify a prognostic LRL signature in colon cancer and elucidated potential biological function. Herein, 10 differential expressed lysosome-related genes were obtained by the TCGA database and ultimately 4 prognostic LRLs for conducting a risk model were identified by the co-expression, univariate cox, least absolute shrinkage and selection operator analyses. Kaplan-Meier analysis, principal-component analysis, functional enrichment annotation, and nomogram were used to verify the risk model. Besides, the association between the prognostic model and immune infiltration, chemotherapeutic drugs sensitivity were also discussed in this study. This risk model based on the LRLs may be promising for potential clinical prognosis and immunotherapeutic responses related indicator in colon cancer patients.


Colonic Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Prognosis , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Nomograms , Lysosomes/genetics , Tumor Microenvironment/genetics
16.
Int J Mol Sci ; 25(2)2024 Jan 13.
Article En | MEDLINE | ID: mdl-38256082

Glutaredoxin 1 (Grx1) is an essential enzyme that regulates redox signal transduction and repairs protein oxidation by reversing S-glutathionylation, an oxidative modification of protein cysteine residues. Grx1 removes glutathione from proteins to restore their reduced state (protein-SH) and regulate protein-SSG levels in redox signaling networks. Thus, it can exert an influence on the development of cancer. To further investigate this problem, we performed an analysis of Grx1 expression in colon adenocarcinoma samples from the Polish population of patients with primary colon adenocarcinoma (stages I and II of colon cancer) and those with regional lymph node metastasis (stage III of colon cancer). Our study revealed a significant correlation between the expression of Grx1 protein through immunohistochemical analysis and various clinical characteristics of patients, such as histological grade, depth of invasion, angioinvasion, staging, regional lymph node invasion, and PCNA expression. It was found that almost 88% of patients with stage I had high levels of Grx1 expression, while only 1% of patients with stage III exhibited high levels of Grx1 protein expression. Furthermore, the study discovered that high levels of Grx1 expression were present in samples of colon mucosa without any pathological changes. These results were supported by in vitro analysis conducted on colorectal cancer cell lines that corresponded to stages I, II, and III of colorectal cancer, using qRT-PCR and Western blot.


Adenocarcinoma , Colonic Neoplasms , Glutaredoxins , Humans , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Glutaredoxins/genetics , Prognosis
18.
Patient Educ Couns ; 119: 108047, 2024 Feb.
Article En | MEDLINE | ID: mdl-37976668

OBJECTIVE: Identify if primary care physicians (PCPs) accurately understand patient preferences for colorectal cancer (CRC) testing, whether shared decision making (SDM) training improves understanding of patient preferences, and whether time spent discussing CRC testing improves understanding of patient preferences. METHODS: Secondary analysis of a trial comparing SDM training plus a reminder arm to a reminder alone arm. PCPs and their patients completed surveys after visits assessing whether they discussed CRC testing, patient testing preference, and time spent discussing CRC testing. We compared patient and PCP responses, calculating concordance between patient-physician dyads. Multilevel models tested for differences in preference concordance by arm or time discussing CRC. RESULTS: 382 PCP and patient survey dyads were identified. Most dyads agreed on whether CRC testing was discussed (82%). Only 52% of dyads agreed on the patient's preference. SDM training did not impact accuracy of PCPs preference diagnoses (55%v.48%,p = 0.22). PCPs were more likely to accurately diagnose patient's preferences when discussions occurred, regardless of length. CONCLUSION: Only half of PCPs accurately identified patient testing preferences. Training did not impact accuracy. Visits where CRC testing was discussed resulted in PCPs better understanding patient preferences. PRACTICE IMPLICATIONS: PCPs should take time to discuss testing and elicit patient preferences.


Colonic Neoplasms , Colorectal Neoplasms , Physicians , Humans , Colonic Neoplasms/diagnosis , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Patient Preference
19.
J Gene Med ; 26(1): e3620, 2024 Jan.
Article En | MEDLINE | ID: mdl-37973153

BACKGROUND: The global prevalence and metastasis rates of colon adenocarcinoma (COAD) are high, and therapeutic success is limited. Although previous research has primarily explored changes in gene phenotypes, the incidence rate of COAD remains unchanged. Metabolic reprogramming is a crucial aspect of cancer research and therapy. The present study aims to develop cluster and polygenic risk prediction models for COAD based on glucose metabolism pathways to assess the survival status of patients and potentially identify novel immunotherapy strategies and related therapeutic targets. METHODS: COAD-specific data (including clinicopathological information and gene expression profiles) were sourced from The Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus (GEO) datasets (GSE33113 and GSE39582). Gene sets related to glucose metabolism were obtained from the MSigDB database. The Gene Set Variation Analysis (GSVA) method was utilized to calculate pathway scores for glucose metabolism. The hclust function in R, part of the Pheatmap package, was used to establish a clustering system. The mutation characteristics of identified clusters were assessed via MOVICS software, and differentially expressed genes (DEGs) were filtered using limma software. Signature analysis was performed using the least absolute shrinkage and selection operator (LASSO) method. Survival curves, survival receiver operating characteristic (ROC) curves and multivariate Cox regression were analyzed to assess the efficacy and accuracy of the signature for prognostic prediction. The pRRophetic program was employed to predict drug sensitivity, with data sourced from the Genomics of Drug Sensitivity in Cancer (GDSC) database. RESULTS: Four COAD subgroups (i.e., C1, C2, C3 and C4) were identified based on glucose metabolism, with the C4 group having higher survival rates. These four clusters were bifurcated into a new Clust2 system (C1 + C2 + C3 and C4). In total, 2175 DEGs were obtained (C1 + C2 + C3 vs. C4), from which 139 prognosis-related genes were identified. ROC curves predicting 1-, 3- and 5-year survival based on a signature containing nine genes showed an area under the curve greater than 0.7. Meanwhile, the study also found this feature to be an important predictor of prognosis in COAD and accordingly assessed the risk score, with higher risk scores being associated with a worse prognosis. The high-risk and low-risk groups responded differently to immunotherapy and chemotherapeutic agents, and there were differences in functional enrichment pathways. CONCLUSIONS: This unique signature based on glucose metabolism may potentially provide a basis for predicting patient prognosis, biological characteristics and more effective immunotherapy strategies for COAD.


Adenocarcinoma , Colonic Neoplasms , Humans , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Colonic Neoplasms/therapy , Adenocarcinoma/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/therapy , Immunotherapy , Carbohydrate Metabolism , Glucose
20.
Gastroenterology ; 166(2): 338-340.e3, 2024 Feb.
Article En | MEDLINE | ID: mdl-37839498

The global burden of colorectal cancer is expected to increase more than 60% by 2030; however, compelling evidence now shows that the implementation of population screening programs in developed countries has led to a substantial reduction in incidence and mortality.1,2 Despite this, patients continue to develop preventable colorectal cancers, in part because of high rates of interval colon cancer diagnosed after screening or surveillance colonoscopies.3.


Adenoma , Colonic Neoplasms , Colonic Polyps , Colorectal Neoplasms , Humans , Colonic Neoplasms/diagnosis , Colonoscopy/methods , Adenoma/diagnostic imaging , Adenoma/epidemiology , Diagnostic Imaging , Incidence , Early Detection of Cancer/methods , Colorectal Neoplasms/diagnosis , Colonic Polyps/diagnosis
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