Spectral histopathology of colon cancer tissue sections by Raman imaging with 532 nm excitation provides label free annotation of lymphocytes, erythrocytes and proliferating nuclei of cancer cells

Abstract Colon cancer is often complicated by thromboembolic episodes. It has been recognized that blood coagulation proteins play a role in malignant tumor progression and metastatic dissemination. An important inhibitory mechanism is provided by protein C (PC) system consisting of protein C, protein S (PS) and thrombomodulin (TM). Thrombin binds to membrane-bound TM and consequently activates PC. Active PC together with its cofactor - PS inactivates coagulation factors Va and VIIIa. Recently novel biological activities have been desribed for protein C system components that do not relate to its hemostatic functions. Active protein C exerts antiapoptotic activity towards endothelial cells (ECs) and activates proteolytic enzymes. It induces proliferation of ECs and angiogenesis. Protein S was documented to inhibit apoptosis as well as inflammatory and immunologic response. The purpose of the study was to elucidate the solid phase interactions between colon cancer tissue and components of protein C system that may contribute to tumor progression. The tissues from colon cancer were obtained at surgical resection during radical treatment of 66 patients. The patients undergoing surgery have not received any previous anticancer therapy. Tumor fragments were processed acc. to AMeX method and than embedded in paraffin. Immunohistochemical studies (avidin-biotin complex-ABC - technique) were performed using polyclonal antibodies against PC, PS and TM. Weak expression of PC was observed in cancer cells of two thirds of the examined specimens while in 4/66 cases there was no staining for PC in cancer cell bodies. One third of colon cancer fragments revealed strong expression of PC. Presence of PS was demonstrated in 64 cases of colon cancer, however its expression was irregular: a weak staining was observed in 60 cases and strong one - only in 4 cases. Two cases of colon cancer tissue have not revealed any staining for PS in cancer cells. Weak expression of TM was observed in two thirds of the examined cases, while a strong staining was revealed in one third of colon cancer tissues. However the expression of TM was inconsistent: not all cell bodies were TM-positive. The presence of PC and PS, but not TM was demonstrated in tumor associated macrophages. Furthermore, PS and TM antigens were localized in tumor stroma. Heterogeneous expression of PC system components in colon cancer tissue may indicate that their biological activity, exerted via their interplay with coagulation/fibrinolysis and regardless of their function in hemostasis, may modulate tumor growth.

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Research for Expression and Prognostic Value of GABRD in Colon Cancer and Coexpressed Gene Network Construction Based on Data Mining

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/5544182 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Tao Liu ◽

Yuejun Fang

Keyword(s):

Data Mining ◽

Colon Cancer ◽

Normal Tissue ◽

Predictive Ability ◽

Gene Interaction ◽

Notch Signaling Pathway ◽

Cancer Tissue ◽

Gamma Aminobutyric Acid ◽

Colon Cancer Tissue ◽

Go Annotation

Colon cancer is one of the top five cancers with the highest incidence rate in the world. In order to better understand the pathogenesis and progression of colon cancer, it is still necessary to investigate the abnormally expressed genes in cancer tissue. In this study, the Oncomine database was used for expression analysis, and it was found that the expression level of gamma-aminobutyric acid type A receptor subunit delta (GABRD) gene was upregulated in colon cancer tissue compared with that in normal tissue. UALCAN was used to analyze the expression of GABRD in different groups of age, gender, cancer stage, N stage, and histological subtype. Then, it was also found that the expression of GABRD in each subgroup of colon cancer tissue was all high compared with that in normal tissue. LinkedOmics was used to screen out the differentially expressed genes related to GABRD expression in colon cancer. GO annotation and KEGG pathway enrichment analyses found that the correlated genes may be related to breast cancer, human papillomavirus infection, Notch signaling pathway, and other pathways. Thereafter, GSEA was performed to obtain GABRD-related kinases, miRNAs, and transcription factors, and gene interaction networks were constructed. It was found that GABRD may be involved in cell cycle regulation. Finally, websites like GEPIA were used to detect the predictive ability of GABRD on the prognosis of patients with colon cancer. Kaplan-Meier analysis suggested that the upregulation of GABRD expression was related to the poor prognosis of patients with colon cancer. Overall, in this study, the potential role and prognostic ability of GABRD in colon cancer were explored through data mining, which can be a clue for further research on GABRD.

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Abstract 5166: Gene expression microarray analysis identifies association of genes in the integrin/fak signaling pathway with claudin-7 in human colon cancer tissue

10.1158/1538-7445.am2016-5166 ◽

2016 ◽

Cited By ~ 1

Author(s):

Lu Kong ◽

Lei Ding

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Signaling Pathway ◽

Human Colon ◽

Cancer Tissue ◽

Gene Expression Microarray ◽

Expression Microarray ◽

Colon Cancer Tissue ◽

Human Colon Cancer ◽

Gene Expression Microarray Analysis

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Abstract 4944: Detection of functional P-selectin ligands expressed on colon cancer tissue using a novel flow-based assay

10.1158/1538-7445.am2016-4944 ◽

2016 ◽

Author(s):

Eric W. Martin ◽

Ramiro Malgor ◽

Vicente A. Resto ◽

Douglas J. Goetz ◽

Monica M. Burdick

Keyword(s):

Colon Cancer ◽

Cancer Tissue ◽

Colon Cancer Tissue ◽

Selectin Ligands

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Two-tier classifier for identifying small objects in histological tissue classification: experiments with colon cancer tissue mapping

Medical Imaging 2019: Digital Pathology ◽

10.1117/12.2512973 ◽

2019 ◽

Author(s):

Chen-Yu Sun ◽

Weiguo Liu ◽

Scott Doyle

Keyword(s):

Colon Cancer ◽

Cancer Tissue ◽

Tissue Classification ◽

Colon Cancer Tissue ◽

Tissue Mapping

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Exploring the efficacy and cellular uptake of sorafenib in colon cancer cells by Raman micro-spectroscopy

The Analyst ◽

10.1039/c8an02029a ◽

2018 ◽

Vol 143 (24) ◽

pp. 6069-6078 ◽

Cited By ~ 5

Author(s):

H. K. Yosef ◽

T. Frick ◽

M. K. Hammoud ◽

A. Maghnouj ◽

S. Hahn ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Cellular Uptake ◽

Raman Microscopy ◽

Label Free ◽

Colon Cancer Cells

This study demonstrates the efficacy and distribution of sorafenib in colon cancer cells by label-free Raman microscopy.

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Identification of alternatively spliced TIMP-1 mRNA in cancer cell lines and colon cancer tissue

Molecular Oncology ◽

10.1016/j.molonc.2007.05.002 ◽

2007 ◽

Vol 1 (2) ◽

pp. 205-215 ◽

Cited By ~ 10

Author(s):

P.A. Usher ◽

A.M. Sieuwerts ◽

A. Bartels ◽

U. Lademann ◽

H.J. Nielsen ◽

...

Keyword(s):

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Cancer Tissue ◽

Colon Cancer Tissue ◽

Alternatively Spliced

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A pilot study of the immunohistochemical pattern of neuropilin-2 (NRP2) labeling and correlation with tumor stage in colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14098 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14098-e14098

Author(s):

Hongliu Sun ◽

Ashleigh M. Kussman ◽

Carol Freeman ◽

Judy Meredith ◽

Kenneth Hensley ◽

...

Keyword(s):

Colon Cancer ◽

Pilot Study ◽

Internal Control ◽

Medical Center ◽

Tumor Grade ◽

Prognostic Indicator ◽

Tumor Stage ◽

Cancer Tissue ◽

Cytoplasmic Staining ◽

Tissue Sections

e14098 Background: Neuropilin 2 (NRP2) is a transmembrane glycoprotein, non-associated with kinase domains, implicated in neovascularization and metastasis of colon cancer. NRP2 has been proposed as a molecular marker for targeted cancer therapy based on its multiple functions in cancer promotion. NRP2 signaling pathway and its expression have been demonstrated in many carcinomas. To the best of our knowledge, no description of the immunohistochemical staining pattern of NRP2 in colon cancer has been published in the English medical literature. The aim of this study is to investigate the NRP2 labelilng pattern in colon cancer and correlate it with tumor stage. Methods: Tumor sections from 35 randomly selected colectomy specimens with colorectal cancer collected during the last three years were retrieved from the University of Toledo Medical Center Department of Pathology archival material. Formalin fixed, paraffin embedded, 4 μm tissue sections containing invasive tumor were immunolabeled with a commercial antibody against NRP2, using a Ventana Benchmark LT automated instrument. Randomized, immunolabeled colon cancer tissue sections were blindly reviewed by two pathologists. Cytoplasmic and nuclear expression of NRP2 by tumor cells was graded as negative (no staining), focal (staining in <50% of cells), and diffuse (staining in ≥ 50% of cells). Adjacent benign colonic mucosa was used as an internal control. Results: No T1 or T2 tumor displayed diffuse nuclear labeling for the NRP2 epitope. In contrast, 13/20 T3 tumors (65%) and 4/4 T4 tumors (100%) displayed diffuse nuclear labeling. The association of diffuse nuclear NRP2 labeling with tumor grade was highly statistically significant (p=0.0055 by Chi-squared test). In contrast to nuclear labeling, cytoplasmic staining was observed in all stages and varied from negative to diffuse, but demonstrated no significant correlation with stage. Conclusions: This pilot study on colon cancer specimens suggests that diffuse nuclear immunolabeling of neuropilin-2 is indicative of a higher tumor stage. This finding suggests a potential use for this marker as a prognostic indicator for colon cancer in small biopsy samples.

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