scholarly journals Anterior Gradient-2 (AGR2) overexpression in colon cancer: a potential prognostic biomarker

2021 ◽  
Author(s):  
Delphine Fessart ◽  
Isabelle Mahouche ◽  
Veronique Brouste ◽  
Valerie Velasco ◽  
Isabelle Soubeyran ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Protein Expression ◽  
Cancer Patients ◽  
Causes Of Death ◽  
Early Stage ◽  
Tumour Microenvironment ◽  
Tissue Samples ◽  
Colon Cancers ◽  
Mrna And Protein Expression ◽  
Protein Disulfide

AbstractAimsColon cancer is one of the most common leading causes of death worldwide. Prognostic at an early stage is an efficient way to decrease mortality. The Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a Protein Disulfide Isomerase (PDI) is highly expressed in various solid tumours and is involved in tumour microenvironment-associated processes such as tumour growth, invasion and metastasis. This study aims at examining the expression of AGR2 protein in colon cancer as its prognostic value in such cancer remains inconclusive.MethodsAGR2 protein expression was determined using immunohistochemistry on human tissue samples issued from a cohort of 82 colorectal carcinomas (Institut Bergonié, Bordeaux, France).ResultsAGR2 protein expression was significantly higher in tumours than in adjacent non-tumour controls. AGR2 expression subgroup analyses indicated that AGR2 low expression in colon cancer patients was significantly associated with worse overall survival. Mucinous colon cancers exhibited higher AGR2 expression levels than non-mucinous cancers. Additionally, tumours with microsatellite instability (MSI) were characterised by a strong upregulation of AGR2 mRNA and protein expression despite an absence of MLH1/MSH2 mutations.ConclusionOur findings indicate that high AGR2 protein expression is correlated with longer patient survival and that AGR2 overexpression is associated with MSI and mucinous-type colorectal cancers. Overall, AGR2 might serve as a biomarker to stratify colon tumours and to contribute to the prognosis of colon cancer patients.

QIM19-124: Does Virtual Navigation Improve Care Continuity and Compliance in Patients With Early Stage Colon Cancer?

2019 ◽  
Vol 17 (3.5) ◽  
pp. QIM19-124
Author(s):  
Dayna Crawford ◽  
Brook Blackmore ◽  
Jeremy Ortega ◽  
Erica Williams
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Stage I ◽  
Stage Iii ◽  
Nccn Guidelines ◽  
Care Continuity ◽  
Colon Cancers ◽  
Follow Up Care

Background: Colon cancer is the 3rd most common cancer in men and women combined, with an occurrence rate of 4.49% for men and 4.15% for women. The 2018 expectation is 50,630 deaths related to colon cancer in the United States (American Cancer Society Facts and Figures 2018). Early detection is increasing with nearly 45% of colon cancers diagnosed as stage I/II (Sarah Cannon Cancer Registry 2015). Treatment for early stage I/II colon cancer patients usually involves surgery then surveillance. On-site navigators perform their duties by patient need and barriers to care. Late stage III/IV colon cancer patients require more assistance and face more barriers, which often leaves early stage I/II patients without an advocate. This disparity can lead to lower rates of follow-up care for early stage I/II patients. Sarah Cannon created a program for virtual colon navigation (VCN) to determine if early stage I/II patients benefit from a virtual navigator who offers support by phone throughout their disease process. Objectives: The goal was to increase early stage I/II patients’ knowledge of their cancer and convey the importance of compliance with follow-up care, such as repeat colonoscopy as recommended by their physician and NCCN Guidelines. Methods: By developing software that utilizes artificial intelligence, Sarah Cannon created an automated process to identify colon cancer patients at the time of diagnosis. This technology then routes positive pathology reports to a VCN who contacts the early stage I/II patients by telephone, ensuring patient connection to the suitable physician for treatment. The VCN helps patients understand their diagnosis, provides education, assesses barriers to care, connects to resources, provides emotional support, and offers assistance with follow-up for physician visits, imaging and procedures such as colonoscopies, based upon NCCN Guidelines and physician guidelines. The VCN also connects stage III/IV patients with an on-site navigator in their region for more hands-on navigation. Results: Through September 2018, Sarah Cannon navigated 734 colon cancers, 332 stage I/II and 402 stage III/IV. With our increased capacity, Sarah Cannon/HCA maintained a 98% rate of follow-up care with new diagnoses of all stages of colon cancer. Conclusions: The VCN program allowed Sarah Cannon/HCA to improve care continuity and compliance based upon NCCN Guidelines for early stage I/II colon cancer patients throughout 5 regions and 37 facilities.

scholarly journals Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323363
Author(s):  
Ester Pagano ◽  
Joshua E Elias ◽  
Georg Schneditz ◽  
Svetlana Saveljeva ◽  
Lorraine M Holland ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumour Growth ◽  
Tumour Microenvironment ◽  
Tube Formation ◽  
Tissue Remodelling ◽  
Colon Cancers ◽  
Inflammatory Bowel ◽  
Ion Pumping ◽  
G Protein Coupled

ObjectivePrimary sclerosing cholangitis (PSC) is in 70% of cases associated with inflammatory bowel disease. The hypermorphic T108M variant of the orphan G protein-coupled receptor GPR35 increases risk for PSC and ulcerative colitis (UC), conditions strongly predisposing for inflammation-associated liver and colon cancer. Lack of GPR35 reduces tumour numbers in mouse models of spontaneous and colitis associated cancer. The tumour microenvironment substantially determines tumour growth, and tumour-associated macrophages are crucial for neovascularisation. We aim to understand the role of the GPR35 pathway in the tumour microenvironment of spontaneous and colitis-associated colon cancers.DesignMice lacking GPR35 on their macrophages underwent models of spontaneous colon cancer or colitis-associated cancer. The role of tumour-associated macrophages was then assessed in biochemical and functional assays.ResultsHere, we show that GPR35 on macrophages is a potent amplifier of tumour growth by stimulating neoangiogenesis and tumour tissue remodelling. Deletion of Gpr35 in macrophages profoundly reduces tumour growth in inflammation-associated and spontaneous tumour models caused by mutant tumour suppressor adenomatous polyposis coli. Neoangiogenesis and matrix metalloproteinase activity is promoted by GPR35 via Na/K-ATPase-dependent ion pumping and Src activation, and is selectively inhibited by a GPR35-specific pepducin. Supernatants from human inducible-pluripotent-stem-cell derived macrophages carrying the UC and PSC risk variant stimulate tube formation by enhancing the release of angiogenic factors.ConclusionsActivation of the GPR35 pathway promotes tumour growth via two separate routes, by directly augmenting proliferation in epithelial cells that express the receptor, and by coordinating macrophages’ ability to create a tumour-permissive environment.

scholarly journals TOP2A is overexpressed and is a therapeutic target for adrenocortical carcinoma

2013 ◽  
Vol 20 (3) ◽  
pp. 361-370 ◽  
Author(s):  
Meenu Jain ◽  
Lisa Zhang ◽  
Mei He ◽  
Ya-Qin Zhang ◽  
Min Shen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Adrenocortical Carcinoma ◽  
Cellular Proliferation ◽  
Locally Advanced ◽  
Tissue Samples ◽  
Anchorage Independent Growth ◽  
Mrna And Protein Expression

Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with no effective therapy for patients with unresectable disease. The aim of the current study was i) to evaluate TOP2A expression and function in human adrenocortical neoplasm and ACC cells and ii) to determine the anticancer activity of agents that target TOP2A. TOP2A mRNA and protein expression levels were evaluated in 112 adrenocortical tissue samples (21 normal adrenal cortex, 80 benign adrenocortical tumors, and 11 ACCs). In vitro siRNA knockdown of TOP2A in ACC cell lines (NCI-H295R and SW13) was used to determine its effect on cellular proliferation, cell cycle, anchorage-independent growth, and cellular invasion. We screened 14 TOP2A inhibitors for their anticancer activity in ACC cells. TOP2A mRNA and protein expression was significantly higher in ACC than in benign and normal adrenocortical tissue samples (P<0.05). Knockdown of TOP2A gene expression in ACC cell lines significantly decreased cell proliferation, anchorage-independent growth, and invasion (P<0.05). A screening assay in NCI-H295R cells showed that 11 of 14 TOP2A inhibitors had antiproliferative activity, 5 of the 14 TOP2A inhibitors had a higher antiproliferative activity than mitotane, and aclarubicin was the agent with the highest activity. Aclarubicin was validated to significantly decrease proliferation and tumor spheroid size in both NCI-H295R and SW13 ACC cell lines (P<0.05). Our results suggest that TOP2A is overexpressed in ACC, regulates cellular proliferation and invasion in ACC cells, and is an attractive target for ACC therapy. Of the TOP2A inhibitors screened, aclarubicin is a good candidate agent to test in future clinical trials for patients with locally advanced and metastatic ACC.

scholarly journals Alteration in the immune microenvironment based on APC status in MSS/pMMR colon cancer data retrieved from TCGA

2020 ◽  
Author(s):  
Haishan Lin ◽  
Hongchao Zhen ◽  
Kun Shan ◽  
Xiaoting Ma ◽  
Bangwei Cao
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Enrichment Analysis ◽  
Tumor Immunotherapy ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Cancer Data ◽  
T Cell Infiltration ◽  
Colon Cancers ◽  
Tumor Immune Microenvironment

Abstract Immunotherapy is currently the most advanced anti-tumor treatment approach. The efficacy of anti-tumor immunotherapy is closely related to the tumor immune microenvironment, including immune cells, infiltration of immune factors, and expression of immune checkpoints. At present, the biomarkers for predicting the efficacy of colon cancer immunotherapy do not cover all colon cancer patients suitable for immunotherapy. In this study, TCGA database was used to identify tumor genotypes suitable for anti-tumor immunotherapy. We found that some of the MSS/pMMR populations, that were initially considered unsuitable for immunotherapy, might actually be suitable. In APC-wt/MSS colon cancer, the expression of PD-1, PD-L1, CTLA4 and CYT（GZMA and PRF1）were increased. Based on calculations done by ESTIMATE and CIBERSORT algorithms, the ImmunoScore and the proportion of CT8+ T cell infiltration is increased in these patients. Enrichment analysis was done to screen signaling pathways involved in immune response, extracellular matrix, and cell adhesion. Tumors from 42 colon cancer patients, including 22 APC-mt/MSS and 20 APC-wt/MSS, were immunohistochemically evaluated for expression of CD8 and PD-L1. And APC-wt/MSS tumors showed significantly higher expression of CD8 and PD-L1 than APC-mt/MSS tumor. Based on the results, we found that some colon cancers of APC-wt/MSS are classified by Tumor Immune Microenvironment types (TIMTs) TMIT I. So that we speculate that APC-wt/MSS colon cancer patients could benefit from anti-tumor immunotherapy.

scholarly journals Extracellular matrix changes in colorectal carcinoma and correlation with lymph node metastasis

2021 ◽  
Author(s):  
Thérèse Rachell Theodoro ◽  
Rodrigo Lorenzetti Serrano ◽  
Karine Corcione Turke ◽  
Sarhan Sydney Saad ◽  
Marcelo Augusto Fontenelle Ribeiro Junior ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Colorectal Carcinoma ◽  
Protein Expression ◽  
Cross Sectional ◽  
Tissue Samples ◽  
Node Metastasis ◽  
Mrna And Protein Expression ◽  
Neoplastic Tissues

AbstractThe process of proliferation and invasion of tumor cells depends on changes in the extracellular matrix (ECM) through the activation of enzymes and alterations in the profile of ECM components. We aimed to investigate the mRNA and protein expression of ECM components such as heparanase (HPSE), heparanase-2 (HPSE2), matrix metalloproteinase-9 (MMP-9), and syndecan-1 (SYND1) in neoplastic and non-neoplastic tissues of patients with colorectal carcinoma (CRC). It is a cross-sectional study in which twenty-four adult patients that had CRC were submitted to resection surgery. We analyzed the expression of HPSE, HPSE2, MMP-9, and SYND1 by quantitative RT-PCR and immunohistochemistry. Differing from most of the studies that compare the mRNA expression between tumor samples and non-neoplastic tissues, we decided to investigate whether variations exist in the expression of the ECM components between the affected tissue and nontumoral tissue collected from the same patient with CRC. We removed both tissue samples immediately after the surgical resection of CRC. The data showed higher mRNA and protein expression of HPSE2 (P = 0.0058), MMP-9 (P = 0.0268), and SYND1 (P = 0.0002) in tumor samples compared to the non-neoplastic tissues, while there was only an increase in the level of HPSE protein in tumor tissues. A greater expression of HPSE2 was observed in patients with lymph node metastasis (P = 0.048), suggesting that such protein can be a marker of lymph node metastasis in CRC.

scholarly journals Exosomal ECM1 protein expression in plasma from the tumor-draining vein (mesenteric vein) and time to relapse in colon cancer patients

2017 ◽  
Vol 28 ◽  
pp. v193-v194
Author(s):  
S. Santasusagna ◽  
A. Navarro ◽  
I. Moreno ◽  
R. Ibeas ◽  
F. Martinez ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Protein Expression ◽  
Cancer Patients ◽  
Mesenteric Vein ◽  
Time To Relapse

Impact of a simple intervention that improves colon cancer lymph node yield and assessement

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15058-e15058
Author(s):  
L. Kowalczyk ◽  
P. Shah ◽  
T. George ◽  
L. Lu ◽  
G. Sarosi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Lymph Node ◽  
Cancer Patients ◽  
Medical Center ◽  
Chi Square ◽  
Lymph Node Yield ◽  
Quality Metric ◽  
Colon Cancers ◽  
National Quality ◽  
Post Test

e15058 Background: The National Quality Forum has endorsed the 12 lymph node (LN) benchmark as a quality metric. Currently, less than 40% of institutions meet this requirement. The purpose of this study was to determine whether implementation of a simple pathology template with dedicated fields for LN reporting led to an increase in the number of colon cancer resections where >12 LNs were reported. Methods: A simple pathology template, derived from the College of American Pathology, using standardized terminology and dedicated fields for LN reporting was implemented in August 2007. Using a pre and post- test design, all consecutive pathology cases were retrospectively reviewed. Inclusion criteria consisted of all stage 0-IV colon cancer patients who underwent surgical resection at a single Veterans Affairs Medical Center. The primary outcome was the percentage of cases in which >12 LNs were assessed between the pre and post-template group. Age, gender, anatomic location, and stage were also collected. Statistical comparisons were made using chi-square and Fisher's exact t-test. Results: 111 pre-template and 71 post-template cases were analyzed. The majority of patients were Caucasian (74%) males (97%). There were no significant differences between the two groups (see Table 1 ), however there was a trend towards more right-sided colon cancers in the pre-template group. 51% of all pre-template pathology reports evaluated >12 LNs compared to 68% of post-template reports (33% improvement in LN yield; p=0.03). Conclusions: Examination of >12 LNs has important therapeutic and prognostic implications in colon cancer patients. Use of a standardized pathology template with dedicated fields for LN reporting is a simple intervention that can increase yield of LN reporting. This can have a significant impact for institutions striving to reach the 12 LN quality metric. [Table: see text] No significant financial relationships to disclose.

scholarly journals The Chemokine CXCL16 Is a New Biomarker for Lymph Node Analysis of Colon Cancer Outcome

2019 ◽  
Vol 20 (22) ◽  
pp. 5793 ◽  
Author(s):  
Manar AbdelMageed ◽  
Haytham Ali ◽  
Lina Olsson ◽  
Gudrun Lindmark ◽  
Marie-Louise Hammarström ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Protein Expression ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Mrna Levels ◽  
Colon Tissue ◽  
Regional Lymph Nodes ◽  
Primary Tumors ◽  
Kaplan Meier ◽  
Cancer Outcome

Chemokines are important in the development and progression of tumors. We investigated the expression of CXCL14 and CXCL16 in colon cancer. Expression of mRNA was assessed in primary tumors and lymph nodes and CXCL16 mRNA levels were correlated to patient’s survival. Protein expression was investigated by two-color immunofluorescence and immunomorphometry. CXCL14 and CXCL16 mRNA levels and protein expression were significantly higher in colon cancer primary tumors compared to apparently normal colon tissue. Positive cells were tumor cells, as revealed by anti-CEA and anti-EpCAM staining. CXCL16, but not CXCL14, mRNA levels were significantly higher in hematoxylin and eosin positive (H&E(+)) compared to H&E(−) colon cancer lymph nodes or control nodes (P < 0.0001). CXCL16 mRNA was expressed in 5/5 colon cancer cell lines while CXCL14 was expressed significantly in only one. Kaplan-Meier analysis revealed that colon cancer patients with lymph nodes expressing high or very high levels (7.2 and 11.4 copies/18S rRNA unit, respectively) of CXCL16 mRNA had a decreased mean survival time of 30 and 46 months at the 12-year follow-up (P = 0.04, P = 0.005, respectively). In conclusion, high expression of CXCL16 mRNA in regional lymph nodes of colon cancer patients is a sign of a poor prognosis.

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