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1.
Clin. transl. oncol. (Print) ; 24(9): 1673-1681, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-JHG-502

RESUMO

Colorectal cancer (CRC) is one of the most common cancers in the world. The incidence rate of cancer is high. The overall response to traditional treatment methods such as surgery, radiotherapy, and chemotherapy is not very satisfactory. Therefore, finding new therapeutic targets is very important for improving CRC treatment. In recent reports, the role of circRNAs in regulating colorectal angiogenesis has been gradually revealed. CircRNAs can indirectly act on angiogenesis pathways and regulate the expression of growth factors such as vascular endothelial growth factor (VEGF). CircRNAs are endogenous noncoding RNAs formed by pre-mRNAs through exon circular splicing. The covalent closed-loop structure makes these RNAs highly conserved and stable. CircRNAs have been found in human plasma, serum, urine, and other body fluids. Their highly conserved characteristics play important roles in many biological activities. CircRNAs can participate in the progression of many diseases by sponging miRNAs, interacting with proteins, and regulating transcription. Angiogenesis can provide nutrients and oxygen for tumour proliferation and metastasis. Angiogenesis is an important sign of the formation of the tumour microenvironment. Here, we will summarize the role of the latest circRNAs in the mechanism of angiogenesis in CRC and provide potential therapeutic targets for clinical treatment. (AU)


Assuntos
Humanos , Neoplasias Colorretais/patologia , MicroRNAs/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Splicing de RNA , Microambiente Tumoral
2.
Clin. transl. oncol. (Print) ; 24(9): 1776–1784, septiembre 2022. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-JHG-510

RESUMO

PurposeThe recently developed fibroblast activation protein inhibitor (FAPI) tracer for PET/CT, binding tumour-stromal cancer-associated fibroblasts, is a promising tool for detection of positive lymph nodes. This study provides an overview of features, including sizes and tumour-stromal content, of lymph nodes and their respective lymph node metastases (LNM) in colorectal cancer (CRC), since literature lacks on whether LNMs contain sufficient stroma to potentially allow FAPI-based tumour detection.MethodsHaematoxylin and eosin-stained tissue slides from 73 stage III colon cancer patients were included. Diameters and areas of all lymph nodes and their LNMs were assessed, the amount of stroma by measuring the stromal compartment area, the conventional and total tumour-stroma ratios (TSR-c and TSR-t, respectively), as well as correlations between these parameters. Also, subgroup analysis using a minimal diameter cut off of 5.0 mm was performed.ResultsIn total, 126 lymph nodes were analysed. Although positive correlations were observed between node and LNM for diameter and area (r = 0.852, p < 0.001 and r = 0.960, p < 0.001, respectively), and also between the LNM stromal compartment area and nodal diameter (r = 0.612, p < 0.001), nodal area (r = 0.747, p < 0.001) and LNM area (r = 0.746, p < 0.001), novel insight was that nearly all (98%) LNMs contained stroma, with median TSR-c scores of 35% (IQR 20–60%) and TSR-t of 20% (IQR 10–30%). Moreover, a total of 32 (25%) positive lymph nodes had a diameter of < 5.0 mm.ConclusionIn LNMs, stroma is abundantly present, independent of size, suggesting a role for FAPI PET/CT in improved lymph node detection in CRC. (AU)


Assuntos
Humanos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Neoplásica/patologia , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos
3.
Clin. transl. oncol. (Print) ; 24(9): 1818–1827, septiembre 2022. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-JHG-514

RESUMO

BackgroundTumor-associated macrophages (TAM) are known to facilitate colorectal cancer (CRC) growth. High macrophage infiltration in thymidine phosphorylase (TYMP) expressing CRC may correspond to poor prognosis. The prognostic impact of the expression CD163, a receptor associated with TAM, and TYMP in stroma, respectively, tumor tissue is not yet established. The aim of this study was to identify the potential associations between TYMP and CD163 expression levels and relapse-free survival (RFS) of patients with stage II CRC, and if microdissection is of importance.MethodsStage II CRC patients, radically resected with relapse (n = 104), were matched to patients with a 5-year relapse-free follow-up (n = 206). Gene expression of TYMP and CD163 was analyzed in snap-frozen tumor tissues and in microdissected formalin-fixed tumor tissues separated into tumor epithelium and stroma.ResultsTYMP expression was high in poorly differentiated tumors, right-sided CRC, and tumors with high microsatellite instability CD163-expressing macrophages near tumor epithelial cells had high expression in poorly differentiated and T4 tumors. High TYMP expression in tumor epithelial cells was in the multivariate analyses associated with shorter relapse-free survival (hazard ratio 1.66; 95% confidence interval: 1.09–2.56; p < 0.05).ConclusionsTYMP expression in tumor epithelial cells was associated with RFS and emphasizes the need for tissue microdissection. Additional studies are needed to establish whether TYMP and CD163 could add clinically relevant information to identify high-risk stage II patients that could benefit from adjuvant chemotherapy. (AU)


Assuntos
Humanos , Antígenos CD/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Receptores de Superfície Celular , Prognóstico
4.
Khirurgiia (Mosk) ; (8): 45-52, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35920222

RESUMO

OBJECTIVE: To analyze patients undergoing redo liver resections for metastatic colorectal cancer. MATERIAL AND METHODS: The study included 14 patients with colorectal cancer who underwent several redo liver resections for metastatic lesions between September 2011 and June 2021. Mean age of patients was 63.5 years. Left-sided colonic G2 adenocarcinoma T4N1-2 prevailed (wild-type KRAS). RESULTS: Fourteen patients (100%) underwent two liver resections, 7 (50%) - three resections, 1 (7.1%) - four resections. Mean period between the first and the second liver resections was 16.2 months, between the second and the third resections - 9.9 months, between the third and the fourth resections - 5 months. Maximum follow-up period after primary surgery was 9 years and 9 months. Seventy-five percent of patients were alive after 34.2 months, 50% - after 58.9 months. N+ status of colorectal tumor decreased survival while KRAS mutation and synchronous metastatic liver lesions increased survival. CONCLUSION: Redo liver resections for metastatic colorectal cancer are safe and ensure favorable long-term survival in certain patients.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Retais , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias Retais/cirurgia , Estudos Retrospectivos
5.
Cell Stem Cell ; 29(8): 1213-1228.e8, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35931031

RESUMO

Intestinal homeostasis is underpinned by LGR5+ve crypt-base columnar stem cells (CBCs), but following injury, dedifferentiation results in the emergence of LGR5-ve regenerative stem cell populations (RSCs), characterized by fetal transcriptional profiles. Neoplasia hijacks regenerative signaling, so we assessed the distribution of CBCs and RSCs in mouse and human intestinal tumors. Using combined molecular-morphological analysis, we demonstrate variable expression of stem cell markers across a range of lesions. The degree of CBC-RSC admixture was associated with both epithelial mutation and microenvironmental signaling disruption and could be mapped across disease molecular subtypes. The CBC-RSC equilibrium was adaptive, with a dynamic response to acute selective pressure, and adaptability was associated with chemoresistance. We propose a fitness landscape model where individual tumors have equilibrated stem cell population distributions along a CBC-RSC phenotypic axis. Cellular plasticity is represented by position shift along this axis and is influenced by cell-intrinsic, extrinsic, and therapeutic selective pressures.


Assuntos
Neoplasias Colorretais , Mucosa Intestinal , Animais , Neoplasias Colorretais/patologia , Homeostase/fisiologia , Humanos , Mucosa Intestinal/metabolismo , Intestinos , Camundongos , Células-Tronco Neoplásicas/patologia , Receptores Acoplados a Proteínas G/metabolismo
6.
Contrast Media Mol Imaging ; 2022: 2387192, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935327

RESUMO

Chemokine C-C motif chemokine ligand 3 (CCL3) plays an important role in the invasion and metastasis of malignant tumors. For developing new therapeutic targets and antitumor drugs, the effect of chemokine CCL3 and the related cytokine network on colorectal cancer should be investigated. This study used cell, tissue, and animal experiments to prove that CCL3 is highly expressed in colorectal cancer and confirmed that CCL3 can promote the proliferation of cancer cells, and its expression is closely related to TRAF6/NF-κB molecular pathway. In addition, protein chip technology was used to examine colorectal cancer tissue samples and identify the key factors of chemokine CCL3 and the toll-like receptors/nuclear factor-κB (TLR/NF-κB) pathway in cancer and metastatic lymph nodes. Furthermore, the lentiviral vector technology was employed for transfection to construct interference and overexpression cell lines. The experimental results reveal the mechanism of CCL3 and TNF receptor-associated factor 6 (TRAF6)/NF-κB pathway-related factors and their effects on the proliferation of colon cancer cells. Finally, the expression and significance of CCL3 in colorectal cancer tissues and its correlation with clinical pathology were studied by immunohistochemistry. Also, the results confirmed that CCL3 and C-C motif chemokine receptor 5 (CCR5) were expressed in adjacent tissues, colorectal cancer tissues, and metastatic cancer. The expression level was correlated with the clinical stage and nerve invasion. The expression of chemokine CCL3 and receptor CCR5 was positively correlated with the expression of TRAF6 and NF-κB and could promote the proliferation, invasion, and migration of colorectal cancer cells through TRAF6 and NF-κB.


Assuntos
Neoplasias Colorretais , NF-kappa B , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CCL3/metabolismo , Quimiocina CCL3/farmacologia , Neoplasias Colorretais/patologia , NF-kappa B/metabolismo , NF-kappa B/farmacologia , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/farmacologia
7.
Pathol Oncol Res ; 28: 1610502, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936516

RESUMO

Colorectal cancer (CRC) is one of the most common cancers worldwide. The patient's prognosis largely depends on the tumor stage at diagnosis. The pathological TNM Classification of Malignant Tumors (pTNM) staging of surgically resected cancers represents the main prognostic factor and guidance for decision-making in CRC patients. However, this approach alone is insufficient as a prognostic predictor because clinical outcomes in patients at the same histological tumor stage can still differ. Recently, significant progress in the treatment of CRC has been made due to improvements in both chemotherapy and surgical management. Immunotherapy-based approaches are one of the most rapidly developing areas of tumor therapy. This review summarizes the current knowledge about the tumor microenvironment (TME), immune response and its interactions with CRC development, immunotherapy and prognosis.


Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Neoplasias Colorretais/patologia , Humanos , Imunidade , Imunoterapia , Prognóstico
8.
BMC Cancer ; 22(1): 861, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933369

RESUMO

BACKGROUND: Tumor budding is associated with lymph node (LN) metastasis in submucosal colorectal cancer (CRC). However, the rate of LN metastasis associated with the number of tumor buds is unknown. Here, we determined the optimal tumor budding cut-off number and developed a composite scoring system (CSS) for estimating LN metastasis of submucosal CRC. METHODS: In total, 395 patients with histologically confirmed T1N0-2M0 CRC were evaluated. The clinicopathological characteristics were subjected to univariate and multivariate analyses. The Akaike information criterion (AIC) values of the multivariate models were evaluated to identify the optimal cut-off number. A CSS for LN metastasis was developed using independent risk factors. RESULTS: The prevalence of LN metastasis was 13.2%. Histological differentiation, lymphatic or venous invasion, and tumor budding were associated with LN metastasis in univariate analyses. In multivariate models adjusted for histological differentiation and lymphatic or venous invasion, the AIC value was lowest for five tumor buds. Unfavorable differentiation (odds ratio [OR], 8.16; 95% confidence interval [CI], 1.80-36.89), lymphatic or venous invasion (OR, 5.91; 95% CI, 2.91-11.97), and five or more tumor buds (OR, 3.01; 95% CI, 1.21-7.69) were independent risk factors. In a CSS using these three risk factors, the rates of LN metastasis were 5.6%, 15.5%, 31.0%, and 52.4% for total composite scores of 0, 1, 2, and ≥ 3, respectively. CONCLUSIONS: For the estimation of LN metastasis in submucosal CRC, the optimal tumor budding cut-off number was five. Our CSS can be utilized to estimate LN metastasis.


Assuntos
Neoplasias Colorretais , Vasos Linfáticos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Invasividade Neoplásica/patologia , Razão de Chances , Estudos Retrospectivos , Fatores de Risco
9.
BMC Cancer ; 22(1): 839, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915403

RESUMO

BACKGROUND: Inflammatory indices and tumor-infiltrating lymphocytes (TILs) have prognostic value in many cancer types. This study aimed to assess the prognostic value of inflammatory indices and evaluate their correlation with survival and presence of TILs in patients with colorectal liver metastasis (CRLM). METHODS: Medical records of 117 patients who underwent hepatectomy for CRLM were retrospectively reviewed. We calculated inflammatory indices comprising the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, C-reactive protein/albumin ratio (CAR), and Glasgow prognostic score (GPS). Furthermore, we evaluated the relationship between these ratios and the GPS and survival rates and immunohistochemical results of tumor-infiltrating CD3+, CD8+, and Foxp3+ lymphocytes. RESULTS: The patients with low CAR values and low GPS had significantly better overall survival as per the log-rank test (p = 0.025 and p = 0.012, respectively). According to the multivariate analysis using the Cox proportional hazard model, the CAR (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.33-0.99; p = 0.048) and GPS (HR, 0.40; 95% CI, 0.19-0.83; p = 0.013) were independent prognostic factors. Additionally, Foxp3+ lymphocytes were more common in samples from the patients with a low CAR (p = 0.041). Moreover, the number of CD3+ TILs was significantly higher in the patients with a low GPS (p = 0.015). CONCLUSIONS: The CAR and GPS are simple, inexpensive, and objective markers associated with predicting survival in patients with CRLM. Moreover, they can predict the presence of Foxp3+ and CD3+ lymphocytes in the invasive margin of a tumor. TRIAL REGISTRATION: Retrospectively registered. https://www.kurume-u.ac.jp/uploaded/attachment/14282.pdf .


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Albuminas , Proteína C-Reativa , Complexo CD3 , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Fatores de Transcrição Forkhead , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Linfócitos/patologia , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Fatores de Transcrição
10.
Nat Commun ; 13(1): 4443, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927254

RESUMO

A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course of their disease. PMs are associated with a poor quality of life, significant morbidity and dismal disease outcome. To improve care for this patient group, a better understanding of the molecular characteristics of CRC-PM is required. Here we present a comprehensive molecular characterization of a cohort of 52 patients. This reveals that CRC-PM represent a distinct CRC molecular subtype, CMS4, but can be further divided in three separate categories, each presenting with unique features. We uncover that the CMS4-associated structural protein Moesin plays a key role in peritoneal dissemination. Finally, we define specific evolutionary features of CRC-PM which indicate that polyclonal metastatic seeding underlies these lesions. Together our results suggest that CRC-PM should be perceived as a distinct disease entity.


Assuntos
Neoplasias Colorretais , Segunda Neoplasia Primária , Neoplasias Peritoneais , Neoplasias Colorretais/patologia , Humanos , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/secundário , Peritônio/metabolismo , Qualidade de Vida
11.
Sci Rep ; 12(1): 13447, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927305

RESUMO

Various omics-based biomarkers related to the occurrence, progression, and prognosis of colorectal cancer (CRC) have been identified. In this study, we attempted to identify gut microbiome-based biomarkers and detect their association with host gene expression in the initiation and progression of CRC by integrating analysis of the gut mucosal metagenome, RNA sequencing, and sociomedical factors. We performed metagenome and RNA sequencing on colonic mucosa samples from 13 patients with advanced CRC (ACRC), 10 patients with high-risk adenoma (HRA), and 7 normal control (NC) individuals. All participants completed a questionnaire on sociomedical factors. The interaction and correlation between changes in the microbiome and gene expression were assessed using bioinformatic analysis. When comparing HRA and NC samples, which can be considered to represent the process of tumor initiation, 28 genes and five microbiome species were analyzed with correlation plots. When comparing ACRC and HRA samples, which can be considered to represent the progression of CRC, seven bacterial species and 21 genes were analyzed. When comparing ACRC and NC samples, 16 genes and five bacterial species were analyzed, and four correlation plots were generated. A network visualizing the relationship between bacterial and host gene expression in the initiation and progression of CRC indicated that Clostridium spiroforme and Tyzzerella nexilis were hub bacteria in the development and progression of CRC. Our study revealed the interactions of and correlation between the colonic mucosal microbiome and host gene expression to identify potential roles of the microbiome in the initiation and progression of CRC. Our results provide gut microbiome-based biomarkers that may be potential diagnostic markers and therapeutic targets in patients with CRC.


Assuntos
Adenoma , Neoplasias Colorretais , Microbioma Gastrointestinal , Microbiota , Adenoma/genética , Adenoma/microbiologia , Bactérias/genética , Neoplasias Colorretais/patologia , Microbioma Gastrointestinal/genética , Expressão Gênica , Humanos , Mucosa Intestinal/patologia , Microbiota/genética
12.
Front Immunol ; 13: 898561, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936004

RESUMO

Background: We previously reported rare regressive genetic trajectories of KRAS pathogenic mutations as a specific hallmark of the genuine oligometastatic status in colorectal cancer (CRC). Methods: Survival and prognostic impact of disease extent in 140 metastatic CRC patients were evaluated through the Kaplan-Meyer curves and the Log-Rank test. KRAS mutations were assessed through the Illumina NovaSeq 6000 platform and TruSight™ Oncology 500 kit. HLA typing was carried out by PCR with sequence-specific oligonucleotides. Lymphocyte densities in tumors were expressed as cells per square millimeter. NKs isolated and CD8+ from NK-depleted PBMCs were characterized through flow cytometry. CD107a externalization was evaluated as NKs/CD8 cytotoxicity toward human colon cancer cells HT29, SW620, HCT116, and LS174T carrying different KRAS mutations. Results: The oligometastatic status was a strong and independent variable for survival (HR: 0.08 vs. polymetastatic disease; 95% CI: 0.02-0.26; p < 0.001). Eighteen oligometastatic patients were selected. Twelve were alive at the last follow-up, and 9 were characterized. Genetic regression of KRAS was observed in 3 patients: patient (PAT)2, PAT5, and PAT8. PAT2 and PAT5 presented the highest levels of GrzB+ lymphocytes in the tumor cores of the metastases (120 ± 11.2 and 132 ± 12.2 cells/mm2, respectively). Six out of 9 patients (67%), including PAT2 and PAT5, expressed HLA-C7. Twopatients (PAT2 and PAT5) presented high CD3+/CD8+-dependent cytotoxicity against HLA-C7+ SW620 cells (p.G12V-mutated cells), which was consistent with their observed mutational regression (p.G12V/p.G13D in primary→p.G13D in metastatic tumor). Conclusions: We provide evidence that CD3+/CD8+ lymphocytes from oligometastatic CRC patients display differential cytotoxicity against human colon cancer cells carrying KRAS mutations. This could provide an interesting basis for monitoring oligometastatic disease and developing future adoptive immunotherapies.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Mutação , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética
13.
Contrast Media Mol Imaging ; 2022: 2279018, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935311

RESUMO

The aim of this research was to investigate the predictive role of texture features in computed tomography (CT) images based on artificial intelligence (AI) algorithms for colorectal liver metastases (CRLM). A total of 150 patients with colorectal cancer who were admitted to the hospital were selected as the research objects and randomly divided into three groups with 50 cases in each group. The patients who were found to suffer from the CRLM in the initial examination were included in group A. Patients who were found with CRLM in the follow-up were assigned to group B (B1: metastasis within 0.5 years, 16 cases; B2: metastasis within 0.5-1.0 years, 17 cases; and B3: metastasis within 1.0-2.0 years, 17 cases). Patients without liver metastases during the initial examination and subsequent follow-up were designated as group C. Image textures were analyzed for patients in each group. The prediction accuracy, sensitivity, and specificity of CRLM in patients with six classifiers were calculated, based on which the receiver operator characteristic (ROC) curves were drawn. The results showed that the logistic regression (LR) classifier had the highest prediction accuracy, sensitivity, and specificity, showing the best prediction effect, followed by the linear discriminant (LD) classifier. The prediction accuracy, sensitivity, and specificity of the LR classifier were higher in group B1 and group B3, and the prediction effect was better than that in group B2. The texture features of CT images based on the AI algorithms showed a good prediction effect on CRLM and had a guiding significance for the early diagnosis and treatment of CRLM. In addition, the LR classifier showed the best prediction effect and high clinical value and can be popularized and applied.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Algoritmos , Inteligência Artificial , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Humanos , Neoplasias Hepáticas/diagnóstico , Tomografia Computadorizada por Raios X/métodos
14.
Cir Cir ; 90(S1): 96-107, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35944108

RESUMO

BACKGROUND: Criteria for resectability of colorectal liver metastases (CRLM) have been expanded over the last decade along with the improvement in chemotherapy. OBJECTIVE: Analyze the differences in several clinicopathological characteristics and overall survival (OS) between patients who underwent an R0 (tumour margin > 1 mm) or R1 (margin < 1 mm) resection. METHOD: Retrospective study including 144 patients with CRLM who underwent a potentially curative liver surgery between 2010 and 2018. Patients are classified according to their surgical margin status (R0 or R1). OS and 17 clinicopathological variables are compared. RESULTS: Both groups are similar and comparable in all the studied variables: age (p = 0.158), sex (p = 0.675), ASA (p = 0.502), tumour location (p = 0.793), tumoral stadium (p = 0.280), post-colectomy chemotherapy (p = 0.664), CRLM synchronicity (p = 0.983) and location (p = 0.078), CEA at diagnosis (p = 0.735), neoadjuvant chemotherapy (p = 0.403), minor/major hepatectomy (p = 0.415), post-operatory complications (p = 0.822) and mortality (p = 0.535), average hospital stay (p = 0.960), post-operative chemotherapy (p = 0.791) and re-hepatectomy (p = 0.530). No significant differences are found in OS a 1, 3 and 5 years (p = 0.160) between patients with R0 and R1 resection. CONCLUSIONS: We consider indicated hepatectomy in any patient with resectable CRLM in whom an R0 resection can be achieved maintaining an adequate hepatic reserve, regardless of the final microscopic resection margin status.


ANTECEDENTES: El avance en oncología ha contribuido a ampliar las indicaciones quirúrgicas de las metástasis hepáticas (MH) del carcinoma colorrectal (CCR). OBJETIVO: Analizar las diferencias en la supervivencia global (SG) y en determinadas características clinicopatológicas entre pacientes con resección R0 (margen tumoral > 1 mm) y R1 (margen < 1 mm). MÉTODO: Estudio retrospectivo con 144 pacientes con MH de CCR intervenidos con intención curativa entre 2010 y 2018, divididos en dos grupos en función del margen de resección (R0 y R1). Se comparan la SG y 17 características clinicopatológicas. RESULTADOS: Ambos grupos son homogéneos y comparables en todas las variables estudiadas: edad (p = 0.158), sexo (p = 0.675), ASA (p = 0.502), localización del CCR (p = 0.793), estadio tumoral (p = 0.280), quimioterapia (QT) adyuvante poscolectomía (p = 0.664), sincronicidad (p = 0.983) y localización (p = 0.078) de las MH, CEA al diagnóstico (p = 0.735), QT neoadyuvante (p = 0.403), hepatectomía mayor/menor (p = 0.415), complicaciones (p = 0.822) y mortalidad posoperatorias (p = 0.535), estancia media (p = 0.960), QT adyuvante poshepatectomía (p = 0.791) y nueva hepatectomía (p = 0.530). Tampoco se observaron diferencias significativas en la SG a 1, 3 y 5 años (p = 0.160) entre pacientes con resección R0 y R1. CONCLUSIONES: Consideramos indicada la hepatectomía en pacientes con MH resecables con posibilidad de conseguir resecciones R0 manteniendo suficiente remanente hepático, independientemente de la afectación microscópica final del margen tumoral.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Margens de Excisão , Estudos Retrospectivos , Taxa de Sobrevida
15.
Med Sci Monit ; 28: e936745, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35945827

RESUMO

BACKGROUND This retrospective study from a single center in China was conducted using data from medical records between 2012 and 2020, to identify hematological factors that distinguish between patients with colorectal carcinoma (CRC) and colorectal adenoma. MATERIAL AND METHODS In this case-control study, 856 eligible patients were randomly divided into a training set (n=600) and a testing set (n=256). Routine blood parameters, blood coagulation, and liver and kidney function parameters were collected. Univariate and multivariate Cox regression analyses were used to explore diagnostic indicators. The values of the area under the curve and calibration curves were used to evaluate the model. RESULTS The study included 325 colorectal adenoma and 531 CRC patients. The prediction model for diagnosing CRC using hemoglobin-to-platelet ratio, fibrinogen-albumin ratio (FAR), albumin-globulin ratio (A/G), platelet-lymphocyte ratio, carcinoembryonic antigen (CEA), and thrombin time (TT) was developed on the basis of the patients grouped into the CRC and colorectal adenoma groups. The prediction model for diagnosing CRC stage was developed using prothrombin time (PT), TT, CEA, A/G, FAR, and HPR. The prediction model for diagnosing CRC grade was developed using PT, TT, A/G, plateletcrit, FAR, and HPR. The AUCs of the 3 prediction models were [0.848, 95% CI: (0.800-0.896)], [0.806, 95% CI: (0.775-0.836)], and [0.829, 95% CI: (0.797-0.860)] in the testing set. CONCLUSIONS Three diagnostic prediction models for early screening of CRC, stage of CRC, and grade of CRC were established through a panel of readily available hematological parameters, which could provide auxiliary tools for early screening of CRC.


Assuntos
Adenoma , Neoplasias Colorretais , Adenoma/patologia , Albuminas , Biomarcadores Tumorais , Antígeno Carcinoembrionário , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Humanos , Estudos Retrospectivos
16.
Theranostics ; 12(12): 5258-5271, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910805

RESUMO

Rationale: Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that selectively marks cancer stem-like cells (CSCs) and promotes malignant progression in colorectal cancer (CRC). However, the exact molecular mechanism by which DCLK1 drives the aggressive phenotype of cancer cells is incompletely determined. Methods: Here, we performed comprehensive genomics and proteomics analyses to identify binding proteins of DCLK1 and discovered X-ray repair cross-complementing 5 (XRCC5). Thus, we explored the biological role and downstream events of the DCLK1/XRCC5 axis in human CRC cells and CRC mouse models. Results: The results of comprehensive bioinformatics analyses suggested that DCLK1-driven CRC aggressiveness is linked to inflammation. Mechanistically, DCLK1 bound and phosphorylated XRCC5, which in turn transcriptionally activated cyclooxygenase-2 expression and enhanced prostaglandin E2 production; these events collectively generated the inflammatory tumor microenvironment and enhanced the aggressive behavior of CRC cells. Consistent with the discovered mechanism, inhibition of DCLK1 kinase activity strongly impaired the tumor seeding and growth capabilities in CRC mouse models. Conclusion: Our study illuminates a novel mechanism that mediates the pro-inflammatory function of CSCs in driving the aggressive phenotype of CRC, broadening the biological function of DCLK1 in CRC.


Assuntos
Neoplasias Colorretais , Quinases Semelhantes a Duplacortina , Animais , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Complemento C5/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Quinases Semelhantes a Duplacortina/metabolismo , Transição Epitelial-Mesenquimal/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Autoantígeno Ku/metabolismo , Camundongos , Células-Tronco Neoplásicas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Microambiente Tumoral/genética , Raios X
17.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(8): 1074-1079, 2022 Aug 06.
Artigo em Chinês | MEDLINE | ID: mdl-35922234

RESUMO

Objective: To compare the application effect of the colonoscopy, fecal immunochemical test (FIT) and novel risk-adapted screening approach in colorectal cancer screening in Xuzhou population. Methods: From May 2018 to April 2019, 4 280 subjects aged 50-74 were recruited from Gulou district, Yunlong district and Quanshan district of Xuzhou. They were randomly assigned to the colonoscopy group (n=863), FIT group (n=1 723) and novel risk-adapted screening approach group (n=1 694) according to the ratio of 1∶2∶2. For the novel risk-adapted screening approach group, after the risk assessment, high-risk subjects were invited to undergo colonoscopy and low-risk subjects were invited to undergo FIT examination. All FIT positive subjects were invited to undergo colonoscopy. Colonoscopy participation rate [(the number of colonoscopies completed/the number of colonoscopies invited to participate)×100%], detection rate of colorectal lesions [(the number of diagnosed patients/the number of colonoscopies completed)×100%], colonoscopy resource load (the number of colonoscopies completed/the number of diagnosed advanced tumors) and FIT resource load in each group were calculated and compared. Results: The age of all subjects was (61±6) years old, including 1 816 males (42.43%). There was no statistically significant difference in the socio-demographic characteristics of the subjects in different screening groups. The colonoscopy participation rate was 22.60% (195/863) in the colonoscopy group, 57.04% (77/135) in the FIT group, and 33.94% (149/439) in the novel risk-adapted screening approach group, respectively. The colonoscopy participation rate was higher in the FIT group than in the colonoscopy group and the novel risk-adapted screening approach group (P<0.001). The colonoscopy participation rate of novel risk-adapted screening group was significantly higher than the colonoscopy group (P<0.001). The detection rates of advanced tumors were 6.67% (13/195), 9.09% (7/77) and 8.72% (13/149), respectively, and the difference was not statistically significant (P>0.05). The colonoscopy resource load (95%CI) was 15 (13-17) in the colonoscopy group, 11 (9-14) in the FIT group and 11 (10-13) in the novel risk-adapted screening approach group, respectively. Among them, the colonoscopy resource load of high-risk individuals in the novel risk-adapted screening approach group was 12 (9-15). FIT resource loads (95%CI) were 207 (196-218) and 88 (83-94) in the FIT group and the novel risk-adapted screening approach group. Conclusion: The combined application of risk-adapted screening approach and FIT may have a good application effect in colorectal cancer screening.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Fezes , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Sangue Oculto
18.
Technol Cancer Res Treat ; 21: 15330338221118717, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35929169

RESUMO

Background: Forkhead box F2, a member of the Forkhead box transcription factor superfamily, plays an important role in several types of cancer. However, the mechanisms of Forkhead box F2 in the progression of colorectal cancer remain unclear. PRUNE2 is closely associated with prostate cancer, neuroblastoma, glioblastoma, and melanoma. The relationship between Forkhead box F2 and PRUNE2 in colorectal cancer remains unknown. Method: We investigated the effects of Forkhead box F2 upregulation on colorectal cancer cell behavior in vitro using Cell Counting Kit-8, colony formation, flow cytometry, Transwell, reverse transcription quantitative polymerase chain reaction and Western blot analyses. Nude mouse xenografts were established to investigate the effect of Forkhead box F2 upregulation on the growth of colorectal cancer cells. Dual-luciferase reporter assays were performed to confirm the Forkhead box F2 regulation of PRUNE2 transcription. A series of in vitro assays was performed in cells with Forkhead box F2 upregulation and PRUNE2 knockdown to elucidate the function and regulatory effects of Forkhead box F2 on PRUNE2 transcription in colorectal cancer. Results: Forkhead box F2 was downregulated in colorectal cancer tissues compared with adjacent tissues. Forkhead box F2 overexpression significantly suppressed the proliferation and invasion of colorectal cancer cells in vitro and in vivo. Moreover, Forkhead box F2 directly targeted PRUNE2 to promote its transcription in colorectal cancer cells. Furthermore, PRUNE2 mediated the Forkhead box F2-regulated proliferation and invasion of colorectal cancer cells. Additionally, we demonstrated a significant positive correlation between Forkhead box F2 and PRUNE2 mRNA levels in colorectal cancer tissues. Conclusion: These results indicated that Forkhead box F2 and PRUNE2 in combination may serve as a prognostic biomarker for colorectal cancer and that Forkhead box F2 upregulation inhibits the proliferation and invasion of colorectal cancer cells by upregulating PRUNE2.


Assuntos
Neoplasias Colorretais , MicroRNAs , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , MicroRNAs/genética , Regulação para Cima/genética
19.
BMC Cancer ; 22(1): 855, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931997

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. However, limited effective biomarkers are associated with the tumorigenesis and prognosis of CRC. METHODS: The present study identified potential signatures from The Cancer Genome Atlas (TCGA) database and further validated the identified biomarkers in CRC tissues by immunohistochemistry (IHC). RESULTS: The expression of insulin-like growth factor 1 receptor (IGF-1R) and Livin gene was significantly upregulated in CRC samples compared to the adjacent normal samples in the TCGA dataset. IHC indicated that IGF-1R and Livin protein levels are increased in CRC and adenoma tissues compared to normal tissues. Notably, the IGF-1R protein levels differed significantly between adenoma and CRC. The elevated IGF-1R and Livin expression was associated with CRC clinicopathological features, including age, gender, histological subtype, individual cancer stages, nodal metastasis, and TP53-mutant in TCGA. Additionally, the IGF-1R promoter methylation level was closely related to CRC. Consistent with the TCGA study, IHC indicated that overexpressed IGF-1R and Livin proteins were independent risk factors for stage and metastasis. A marked correlation was established between IGF-1R and Livin expression in CRC, while the survival map showed no significant correlation with CRC. Kaplan-Meier survival curves showed that CRC patients with high IGF-1R or Livin expression had a prolonged overall disease-free survival than those with low expression in TCGA. CONCLUSION: IGF-1R and Livin are associated with CRC tumorigenesis and might be valuable for novel biomarker identification and targeted therapeutic strategy development.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Colorretais , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas de Neoplasias/metabolismo , Receptor IGF Tipo 1/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinogênese/patologia , Neoplasias Colorretais/patologia , Humanos , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose/análise , Proteínas de Neoplasias/análise , Estadiamento de Neoplasias , Prognóstico , Receptor IGF Tipo 1/análise , Receptor IGF Tipo 1/genética
20.
Dis Markers ; 2022: 4433270, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909892

RESUMO

Background: Alternative splicing (AS) plays a crucial role in regulating the progression of colorectal cancer (CRC), but its distribution remains to be explored. Here, we aim to investigate the genes edited by AS which show differential expression in patients with mismatch repair deficiency (dMMR)/microsatellite instability (MSI). Materials and Methods: We applied long-read nanopore sequencing to determine the mRNA profiles and screen AS genes using Oxford Nanopore Technologies (ONT) method in ten paired CRC tissues. CRC tissue and plasma samples were used to validate the differential genes with AS using real-time fluorescent quantitative PCR, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ONT sequencing identified 404 genes were downregulated, and 348 genes were upregulated in MSI cancer tissues compared with microsatellite stability (MSS) cancer tissues. In total, 6,200 AS events were identified in 2,728 mRNA transcripts. WGCNA revealed dMMR/MSI-correlated gene modules, including INHBA and RPL22L1, which were upregulated; conversely, HMGCS2 was downregulated in MSI cancer. Overexpression of RPL22L1, INHBA, and CAPZA1 was further confirmed in CRC tissues. INHBA was found to be associated with tumor lymphatic metastasis. Importantly, the levels of INHBA in CRC plasma were significantly increased compared with those in noncancer plasma. INHBA showed a higher level in dMMR/MSI CRC than in MSS CRC, indicating that INHBA is a useful biomarker. Conclusion: Our results showed that ONT-identified genes provide a pool to explore AS-associated markers for dMMR/MSI CRC. We demonstrated INHBA as a promising signature for clinical application in predicting tumor lymphatic metastasis and screening dMMR/MSI candidates.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Sequenciamento por Nanoporos , Processamento Alternativo , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA/genética , Humanos , Metástase Linfática , Instabilidade de Microssatélites , RNA Mensageiro/genética
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