scholarly journals Fecal galectin-1 as a potential marker for colorectal cancer and disease severity

2019 ◽  
Vol 76 (10) ◽  
pp. 1037-1044 ◽  
Author(s):  
Milan Jovanovic ◽  
Nevena Gajovic ◽  
Natasa Zdravkovic ◽  
Marina Jovanovic ◽  
Milena Jurisevic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Tissue ◽  
Liquid Fraction ◽  
Interleukin 1 ◽  
Blood Vessel Invasion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Marker ◽  
Histological Differentiation ◽  
Potential Marker ◽  
Advanced Tumor

Background/Aim. Colorectal cancer (CRC) represents one of the most common cancers worldwide. CRC is frequently diagnosed at advanced stages with poor prognosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine systemic and fecal values of galectin- 1 (gal-1) and ratios between gal-1 and proinflammatory cytokines: tumor necrosis factor-alpha (TNF-?), interleukin-1 beta (IL-1?) and interferon gamma (IFN-?), in the patients with CRC and the relationship with clinicopathological aspects of the disease. Methods. The blood samples and feces liquid fraction of 58 patients with CRC were analyzed. The serum and fecal levels of TNF-?, IL-1? and IFN-? and gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Results. The fecal level of gal-1 was increased in the CRC patients with higher nuclear grade and poor tumor tissue differentiation. The gal-1/TNF-? ratio in the serum and feces had a higher trend in the patients with the advanced tumor-nodemetastasis (TNM) stage as well as the detectable lymphatic and blood vessel invasion. The gal-1/TNF-? and gal-1/IFN-? ratios were increased in the serum of patients with presence of lung/liver metastasis or peritoneal carcinomatosis, while the enhanced gal-1/IL-1 ratio was detected only in the serum of patients with lung metastasis. A positive correlation between the gal-1 value in feces and histological differentiation of tumor and biomarkers alpha-fetoprotein (AFP) and cancer antigen- 19-9 (CA 19-9), respectively, was also observed. The fecal values of gal-1 higher than 13,708.29 pg/g presented a highly sensitive and specific marker for histological differentiation of tumor tissue. Conclusion. We believe that the predomination of gal-1 over pro-inflammatory cytokines TNF-?, IL-1? and IFN- ? in the patients with advanced and progressive CRC may implicate on an immunomodulatory role of gal-1 in the limiting ongoing proinflammatory processes. The fecal values of gal-1 can be used as a valuable marker for the severity of CRC.

scholarly journals Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Milan Jovanovic ◽  
Nevena Gajovic ◽  
Natasa Zdravkovic ◽  
Marina Jovanovic ◽  
Milena Jurisevic ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Tumor Tissue ◽  
Tnm Stage ◽  
Nuclear Grade ◽  
Blood Vessel Invasion ◽  
Histological Differentiation ◽  
Galectin 3 ◽  
Valuable Marker ◽  
Anti Inflammatory ◽  
The Relationship

Background and Objectives. The aim of the study was to determine systemic and fecal values of galectin-3 and pro- and anti-inflammatory cytokines in patients with CRC and the relationship with clinicopathological aspects. Methods. Concentrations of galectin-3, TNF-α, TGF-β, IL-10, and IL-1β were analyzed in samples of blood and stool of 60 patients with CRC. Results. Systemic concentration of TNF-α was significantly lower in patients with severe diseases (advanced TNM stage, nuclear grade, and poor histological differentiation) as in patients with more progressive CRC (lymph and blood vessel invasion, presence of metastasis). Fecal values of anti-inflammatory cytokines TGF-β and IL-10 were increased in patients with severe stadium of CRC. Fecal concentration of Gal-3 was enhanced in CRC patients with higher nuclear grade, poor tumor tissue differentiation, advanced TNM stage, and metastatic disease. Gal-3/TNF-α ratio in sera and feces had a higher trend in patients with severe and advanced diseases. Positive correlation between fecal Gal-3 and disease severity, tumor progression, and biomarkers AFP and CEA, respectively, was also observed. Conclusions. Predomination of Gal-3 in patients with advanced diseases may implicate on its role in limiting ongoing proinflammatory processes. The fecal values of Gal-3 can be used as a valuable marker for CRC severity and progression.

scholarly journals Cytoplasmic Expression of DCLK1-S, a Novel DCLK1 Isoform, Is Associated with Tumor Aggressiveness and Worse Disease-Specific Survival in Colorectal Cancer

2021 ◽  
Author(s):  
Elham Kalantari ◽  
Roya Ghods ◽  
Leili Saeednejad Zanjani ◽  
Mandana Rahimi ◽  
Leila Eini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Polyclonal Antibody ◽  
Prognostic Significance ◽  
Rank Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease Specific Survival ◽  
Cytoplasmic Expression ◽  
Advanced Tumor ◽  
Disease Specific

Abstract Background: Oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC). Isoform-specific function of DCLK1 has highlighted key role of the DCLK1-S (short isoform) in tumor maintenance, progression, and invasion. Considering the lack of commercial anti-DCLK1-S antibody suitable for immunohistochemical (IHC) application, this study was conducted to produce and validate an anti-DCLK1-S polyclonal antibody in order to specifically evaluate expression pattern and clinical significance of short isoform of DCLK1 in colorectal cancer tissues.Methods: Rabbit immunization was performed against a synthetic peptide corresponding to the published six specific amino acid sequences of DCLK1-S, and production of antibody was evaluated by enzyme-linked immunosorbent assay (ELISA). After IHC assessment of the purified anti-DCLK1-S polyclonal antibody, it was used to undertake a definitive study for determining prognostic significance of DCLK1-S expression in a well-defined tissue microarray (TMA) series including 348 CRC and 51 adjacent normal tissues with a follow-up period of 108 months. Results: Positive immunoreactivity of DCLK1-S was found in 84.2% of CRC samples. Cytoplasmic expression was the main localization of DCLK1-S compared to nuclear and membranous area of tumor cells. Expression of DCLK1-S in CRC samples was significantly higher compared to adjacent normal samples (P <0.001). A positive significant association was found between high cytoplasmic expression of DCLK1-S and advanced tumor, nodes, and metastases (TNM) stage (P<0.001) as well as the increased tumor differentiation (P= 0.02). Moreover, the patients with CRC whose tumors showed higher cytoplasmic expression of DCLK1-S had worse disease-specific survival (DSS) (log-rank test, P = 0.03) and 5-year DSS rate (P= 0.01). Additionally, the improved prognostic value was seen in the patients with CRC with high DCLK1-S expression versus moderate expression (HR: 2.70, 95% CI: 0.98-7.38; p =0.04) by multivariate analysis.Conclusions: Our findings strongly supported that DCLK1-S isoform may play a crucial role in invasion, tumor aggressive behavior, and worsened DSS of the patients with CRC. Importantly, high cytoplasmic expression of DCLK1-S compared to moderate expression could be considered as an independent prognostic factor influencing DSS. Taken together, DCLK1-S can be a candidate as a promising prognostic and targeted-therapeutic indicator for effective treatment of CRC.

scholarly journals High Expression of MMP-9 in Primary Tumors and High Preoperative MPO in Serum Predict Improved Prognosis in Colorectal Cancer with Operable Liver Metastases

Oncology ◽  
2020 ◽  
pp. 1-17
Author(s):  
Reetta Peltonen ◽  
Jaana Hagström ◽  
Taina Tervahartiala ◽  
Timo Sorsa ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Tumor Tissue ◽  
Prognostic Significance ◽  
Colorectal Tumor ◽  
High Expression ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Tumors ◽  
Cox Regression Analysis ◽  
Postoperative Serum

<b><i>Introduction:</i></b> The liver metastases of colorectal cancer (CRC) can be surgically treated in selected cases, with continuously improving results. Matrix metalloproteinases (MMPs) contribute to cancer invasion by degrading the extracellular matrix, and elevated levels of MMP-2, MMP-8, and MMP-9 have been detected in several malignancies. Myeloperoxidase (MPO) is a mediator of tissue damage that can oxidatively activate latent MMPs. We evaluated the prognostic value of MMP-2, MMP-8, and MMP-9 in tissue samples of primary tumors and liver metastases and the pre- and postoperative serum levels of MMP-8, MMP-9, and MPO in CRC patients undergoing liver resection. <b><i>Methods:</i></b> Tissue and serum samples were obtained from 111 patients who had primary colorectal tumors and their liver metastases surgically treated at the Helsinki University Hospital between 1988 and 2007. Tissue expression of MMP-2, MMP-8, and MMP-9 in primary tumors and liver metastases was evaluated by immunohistochemistry. Pre- and postoperative serum concentrations of MMP-8, MMP-9, and MPO were determined using a time-resolved immunofluorometric assay or commercially available enzyme-linked immunosorbent assay kits. Clinical data were retrieved from patient records and the Central Statistical Office of Finland. Associations with disease-free survival (DFS) and overall survival (OS) were estimated using Cox regression analysis and the Kaplan-Meier method. <b><i>Results:</i></b> High expression of MMP-9 in colorectal tumor tissue was associated with better DFS (<i>p</i> = 0.010), and high preoperative MPO in serum with improved DFS and OS (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.014, respectively). The prognostic significance varied according to gender, age, and the synchronicity of liver metastases. <b><i>Conclusion:</i></b> Low preoperative MPO in serum might identify patients at high risk of recurrence and death after resection of colorectal liver metastases. Elevated preoperative MPO and high expression of MMP-9 in colorectal tumor tissue indicate an improved prognosis. The use of these biomarkers should be adjusted according to clinical characteristics.

scholarly journals Anemia of inflammation in patients with colorectal cancer: Correlation with Interleukin-1, Interleukin-33 and Galectin-1

2021 ◽  
Author(s):  
Miodrag Jocic
Keyword(s):  
Colorectal Cancer ◽  
Interleukin 1 ◽  
Roc Curves ◽  
Microcytic Anemia ◽  
Blood Vessel Invasion ◽  
Range Analysis ◽  
Mutual Correlation ◽  
Interleukin 33 ◽  
Colorectal Cancer Patients ◽  
Anemia Of Inflammation

Purpose: Patients with colorectal cancer (CRC) have anemia often present as a consequence of chronic bleeding from tumor. The exact role of lL-33, Galectin-l and IL-l in the pathological genesis of anemia in colorectal cancer patients has not been elucidated yet. The main goal of this research was to analyze Gal-l, IL-l and lL-33 systemic values in anemic and non-anemic CRC patients. Methods: Concentrations of IL-33, Galectin-1 and IL-1 have been studied in blood samples of 55 CRC patients (27 without anemia and 28 with anemia). Results: CRC patients with anemia had more severe and local advanced disease compared to CRC non-anemic patients. Anemia positively correlated with higher nuclear grade, lymph and blood vessel invasion, as well as with higher TNM stage, detectable metastatic lesions in lung and liver and peritoneal carcinomatosis. Significantly higher IL-33, Gal-1 and IL-1 concentration have been found in sera of patients with CRC and detected anemia. CRC patients mostly had microcytic anemia, while ferritin values were in normal range. Analysis revealed positive mutual correlation between serum values of galectin-1, IL-1 and IL-33 in CRC patients. Level of hemoglobin negatively correlated with serum IL-33, Gal-1 and IL-1. We have analyzed the Receiver Operating Characteristic (ROC) curves of serum IL-33, Gal-1 and IL-1 showed that these cytokines can be treated as additional markers for anemia of inflammation in CRC patients. Conclusions: Predomination of Galectin-1, IL-1 and IL-33 in anemic CRC patients implicates on their potential role in anemia genesis and further development.

scholarly journals Metadherin (MTDH) Overexpression Significantly Correlates with Advanced Tumor Grade and Stages among Colorectal Cancer Patients

2021 ◽  
Author(s):  
Aimen Sultan ◽  
Namood-e Sahar ◽  
Syeda Kiran Riaz ◽  
Javeria Qadir ◽  
Shahzad Hussain Waqar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Tumor Tissue ◽  
Tumor Grade ◽  
Ki 67 ◽  
Core Element ◽  
Age And Gender ◽  
Tissue Samples ◽  
Advanced Tumor ◽  
And Gender

Abstract BackgroundColorectal cancer is the 4th leading cause of cancer related deaths affecting both men and women worldwide. In the present study, any probable role of MTDH mRNA expression in CRC tumorigenesis was explored using both discovery and validation cohorts. Methods and resultsAfter prior ethical and biosafety approvals, tumor tissue samples along with their adjacent controls were collected for this study from Pakistani patients diagnosed with colorectal cancer. RNA was isolated using Trizol reagent, followed by cDNA synthesis. Transcript analysis of MTDH was performed by using qPCR. Moreover, genome-wide expression of MTDH was also determined through micro-array data analysis using BRB- Array Tools software. MTDH expression was significantly high in tumor tissue samples (p<0.05) compared to their respective controls. Likewise, results of microarray analysis also revealed overamplification of MTDH in tumor samples as compared to controls. Expression of MTDH was also found to be positively correlated with KI-67 index (p<0.05) and were observed to be significantly upregulated in advance tumor grade (p< 0.05) and stage (p< 0.05). However, no association of MTDH overexpression with age and gender could be established. ConclusionHence, it can be concluded that MTDH is a core element that plays a pivotal role in colorectal tumorigenesis irrespective of patient’s age and gender. Molecular insight into the tumor microenvironment revealed MTDH as a niche, representing distinctive framework for cancer progression, thus, making it an innovative target strategy for colorectal cancer treatment.

scholarly journals Development, Optimization, and In Vitro Evaluation of Novel Oral Long-Acting Resveratrol Nanocomposite In-Situ Gelling Film in the Treatment of Colorectal Cancer

Gels ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 276
Author(s):  
Shadab Md ◽  
Samaa Abdullah ◽  
Nabil A. Alhakamy ◽  
Waleed S. Alharbi ◽  
Javed Ahmad ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Release ◽  
Encapsulation Efficiency ◽  
Interleukin 1 ◽  
B Cell Lymphoma ◽  
Enzyme Linked Immunosorbent Assay ◽  
Drug Release Profile ◽  
Long Acting ◽  
In Situ Gelling

this study aimed to develop and evaluate sustained-release (SR) long-acting oral nanocomposites in-situ gelling films of resveratrol (Rv) to treat colorectal cancer. In these formulations, Rv-Soy protein (Rv-Sp) wet granules were prepared by the kneading method and then encapsulated in the sodium alginate (NA) dry films. The prepared nanocomposite in-situ gels films were characterized using dynamic light scattering, Fourier-transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The optimized formulations were further evaluated based on drug encapsulation efficiency, pH-drug release profile, swelling study, and storage time effects. The optimized formulation was tested for its anticancer activity against colorectal cancer cells using the cytotoxicity assessment, apoptosis testing, cell cycle analysis, gene expression analysis, and protein estimation by the reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. The optimum film showed encapsulation efficiency of 97.87% ± 0.51 and drug release of 14.45% ± 0.043 after 8 h. All physiochemical characterizations confirmed, reasoned, and supported the drug release experiment’s findings and the encapsulation assay. The Rv nanocomposite formulation showed concentration-dependent cytotoxicity enhanced apoptotic activity as compared to free Rv (p < 0.05). In addition, Rv nanocomposite formulation caused a significant increase in Bcl-2-associated protein X (Bax) and a decrease in expression of B-cell lymphoma 2, interleukin 1 beta, IL-6, and tumor necrosis factor-alpha (Bcl2, IL-1β, IL-6, and TNF-α respectively) compared to that of free Rv in HCT-116 cells. These results suggest that long-acting Rv nanocomposite gels could be a promising agent for colorectal cancer treatment.

scholarly journals Morphofunctional malignancy grading is a valuable prognostic factor for colorectal cancer

2010 ◽  
Vol 47 (3) ◽  
pp. 225-232 ◽  
Author(s):  
Denise Gonçalves Priolli ◽  
Carlos Augusto Real Martinez ◽  
Helenice Piovesan ◽  
Izilda Aparecida Cardinalli ◽  
Nelson Fontana Margarido ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Functional Characterization ◽  
Tissue Expression ◽  
Cell Polarization ◽  
Blood Levels ◽  
Computer Assisted ◽  
Histological Differentiation ◽  
Advanced Tumor ◽  
Tumor Stages

CONTEXT: Novel strategies are needed to identify more efficient biomarkers to accurately diagnose prognose and improve the treatment outcome of colorectal cancer. OBJECTIVES: To analyze the functional and morphological features of colorectal cancer to identify the neoplastic patterns that affect patient survival. METHODS: Forty-five patients with colorectal cancer were followed for a minimum of 3 years. Blood levels of carcinoembryonic antigen (CEA) were measured by chemiluminescence and immunohistochemical analysis of tissue expression followed by computer-assisted image processing. Tumors were assigned to three morphofunctional classes. The morphofunctional classification was based on combination between histological differentiation and cell polarization. The functional characterization was based on the CEA cell polarization. The tissue polarization of CEA was classified in well-polarized, moderately polarized or nonpolarized cells. Morphofunctional staging was defined by the association between morphofunctional class (polarization and histological differentiation) and TNM by score given to each one classification. RESULTS: There was an association between increased CEA tissue expression and loss of histological differentiation (P = 0.01) or loss of polarization capacity (P = 0.03). There was a progressive increase in tissue CEA quantities in accordance with the proposed morphofunctional grading system. Plasma levels of CEA were increased in advanced tumor stages. Blood levels of CEA were increased in advanced morphofunctional stages (P = 0.001). There was a relationship between survival outcome and morphofunctional staging (P = 0.005). CONCLUSION: Morphofunctional staging is a valuable prognostic factor for colorectal cancer and it correlates with plasma CEA levels.

scholarly journals Increased IL-33 And IL-17 in Colorectal Carcinoma Patients with Severe Disease

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Veljko Maric ◽  
Milan Jovanovic ◽  
Natasa Zdravkovic ◽  
Marina Jovanovic ◽  
Nevena Gajovic ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Peritoneal Carcinomatosis ◽  
Poor Prognosis ◽  
Tumor Tissue ◽  
Liquid Fraction ◽  
Severe Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Samples ◽  
Advanced Stages ◽  
The Relationship

Abstract Colorectal cancer (CRC) represents one of the most common cancers. It is frequently diagnosed at advanced stages, indicating on need for new diagnostic markers. Th e aim of this study was to determine systemic and fecal values of IL- 17 and IL-33 in patients with CRC and the relationship with clinicopathological aspects of disease. Th e blood samples and feces liquid fraction of 50 patients with CRC were analyzed. Serum and fecal levels of IL-33 and IL-17 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Fecal levels of IL-33 and IL-17 were increased in CRC patients with poor tumor tissue diff erentiation. Serum IL-33 and fecal IL-17 were increased in patients with presence of lung/liver metastasis or peritoneal carcinomatosis, respectively, while enhanced fecal IL-33 was detected only in patients with peritoneal carcinomatosis. Positive correlation between IL-33 and IL-17 values in sera and feces, respectively was also observed. We believe that increased local values of IL-33 and IL-17, reflected trough higher fecal concentration, in CRC patients with poor tumor tissue differentiation and with presence of lung/liver metastasis or peritoneal carcinomatosis may be considered as a sign of the tumor’s malignant progression and, consequently, of a poor prognosis for patients.

Role of inflammation in the development of colorectal cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
R. Ileng Kumaran ◽  
Kokelavani Nampalli Babu ◽  
Sneha Krishnamoorthy ◽  
Akash Guruswamy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Interleukin 1 ◽  
Cell Types ◽  
Model Systems ◽  
Cytokine Gene Expression ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

scholarly journals PRMT1 enhances oncogenic arginine methylation of NONO in colorectal cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Xin-Ke Yin ◽  
Yun-Long Wang ◽  
Fei Wang ◽  
Wei-Xing Feng ◽  
Shao-Mei Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Locally Advanced ◽  
Xenograft Model ◽  
Arginine Methylation ◽  
Mass Spectrometry Analysis ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Potential Marker

AbstractArginine methylation is an important posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs). However, the role of PRMTs in colorectal cancer (CRC) progression is not well understood. Here we report that non-POU domain-containing octamer-binding protein (NONO) is overexpressed in CRC tissue and is a potential marker for poor prognosis in CRC patients. NONO silencing resulted in decreased proliferation, migration, and invasion of CRC cells, whereas overexpression had the opposite effect. In a xenograft model, tumors derived from NONO-deficient CRC cells were smaller than those derived from wild-type (WT) cells, and PRMT1 inhibition blocked CRC xenograft progression. A mass spectrometry analysis indicated that NONO is a substrate of PRMT1. R251 of NONO was asymmetrically dimethylated by PRMT1 in vitro and in vivo. Compared to NONO WT cells, NONO R251K mutant-expressing CRC cells showed reduced proliferation, migration, and invasion, and PRMT1 knockdown or pharmacological inhibition abrogated the malignant phenotype associated with NONO asymmetric dimethylation in both KRAS WT and mutant CRC cells. Compared to adjacent normal tissue, PRMT1 was highly expressed in the CRC zone in clinical specimens, which was correlated with poor overall survival in patients with locally advanced CRC. These results demonstrate that PRMT1-mediated methylation of NONO at R251 promotes CRC growth and metastasis, and suggest that PRMT1 inhibition may be an effective therapeutic strategy for CRC treatment regardless of KRAS mutation status.

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