Association of gene and protein expression and genetic polymorphism of CC chemokine ligand 4 in colorectal cancer

AbstractThe backbone of all colorectal cancer classifications including the consensus molecular subtypes (CMS) highlights microsatellite instability (MSI) as a key molecular pathway. Although mucinous histology (generally defined as >50% extracellular mucin-to-tumor area) is a “typical” feature of MSI, it is not limited to this subgroup. Here, we investigate the association of CMS classification and mucin-to-tumor area quantified using a deep learning algorithm, and the expression of specific mucins in predicting CMS groups and clinical outcome. A weakly supervised segmentation method was developed to quantify extracellular mucin-to-tumor area in H&E images. Performance was compared to two pathologists’ scores, then applied to two cohorts: (1) TCGA (n = 871 slides/412 patients) used for mucin-CMS group correlation and (2) Bern (n = 775 slides/517 patients) for histopathological correlations and next-generation Tissue Microarray construction. TCGA and CPTAC (n = 85 patients) were used to further validate mucin detection and CMS classification by gene and protein expression analysis for MUC2, MUC4, MUC5AC and MUC5B. An excellent inter-observer agreement between pathologists’ scores and the algorithm was obtained (ICC = 0.92). In TCGA, mucinous tumors were predominantly CMS1 (25.7%), CMS3 (24.6%) and CMS4 (16.2%). Average mucin in CMS2 was 1.8%, indicating negligible amounts. RNA and protein expression of MUC2, MUC4, MUC5AC and MUC5B were low-to-absent in CMS2. MUC5AC protein expression correlated with aggressive tumor features (e.g., distant metastases (p = 0.0334), BRAF mutation (p < 0.0001), mismatch repair-deficiency (p < 0.0001), and unfavorable 5-year overall survival (44% versus 65% for positive/negative staining). MUC2 expression showed the opposite trend, correlating with less lymphatic (p = 0.0096) and venous vessel invasion (p = 0.0023), no impact on survival.The absence of mucin-expressing tumors in CMS2 provides an important phenotype-genotype correlation. Together with MSI, mucinous histology may help predict CMS classification using only histopathology and should be considered in future image classifiers of molecular subtypes.

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Lysine demethylase 5B suppresses CC chemokine ligand 14 to promote progression of colorectal cancer through the Wnt/β-catenin pathway

Life Sciences ◽

10.1016/j.lfs.2020.118726 ◽

2021 ◽

Vol 264 ◽

pp. 118726

Author(s):

Guoqiang Yan ◽

Shiquan Li ◽

Meng Yue ◽

Chenyao Li ◽

Zhenhua Kang

Keyword(s):

Colorectal Cancer ◽

Cc Chemokine ◽

Chemokine Ligand ◽

Lysine Demethylase

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Added Value of Combined Gene and Protein Expression of CK20 and CEA in Non—macroscopically Involved Lymph Nodes of Colorectal Cancer

International Journal of Surgical Pathology ◽

10.1177/1066896908328574 ◽

2008 ◽

Vol 17 (2) ◽

pp. 93-98 ◽

Cited By ~ 4

Author(s):

Giuseppe D'Armento ◽

Lorenzo Daniele ◽

Sara Mariani ◽

Davide Ottaviani ◽

Antonio Mussa ◽

...

Keyword(s):

Colorectal Cancer ◽

Protein Expression ◽

Lymph Nodes ◽

Added Value ◽

Gene And Protein Expression

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CC chemokine ligand 7 expression in liver metastasis of colorectal cancer

Oncology Reports ◽

10.3892/or.2012.1815 ◽

2012 ◽

Vol 28 (2) ◽

pp. 689-694 ◽

Cited By ~ 26

Author(s):

YONG BEOM CHO ◽

WOO YONG LEE ◽

SO-JUNG CHOI ◽

JHINGOOK KIM ◽

HYE KYUNG HONG ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Cc Chemokine ◽

Chemokine Ligand

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Tribbles Pseudokinases in Colorectal Cancer

Cancers ◽

10.3390/cancers13112825 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2825

Author(s):

Bibiana I. Ferreira ◽

Bruno Santos ◽

Wolfgang Link ◽

Ana Luísa De Sousa-Coelho

Keyword(s):

Colorectal Cancer ◽

Tumor Suppressor ◽

Protein Expression ◽

Tumor Suppressor Genes ◽

Current Knowledge ◽

Pharmacological Modulation ◽

Cellular Processes ◽

Gene And Protein Expression ◽

Potential Biomarkers

The Tribbles family of pseudokinases controls a wide number of processes during cancer on-set and progression. However, the exact contribution of each of the three family members is still to be defined. Their function appears to be context-dependent as they can act as oncogenes or tumor suppressor genes. They act as scaffolds modulating the activity of several signaling pathways involved in different cellular processes. In this review, we discuss the state-of-knowledge for TRIB1, TRIB2 and TRIB3 in the development and progression of colorectal cancer. We take a perspective look at the role of Tribbles proteins as potential biomarkers and therapeutic targets. Specifically, we chronologically systematized all available articles since 2003 until 2020, for which Tribbles were associated with colorectal cancer human samples or cell lines. Herein, we discuss: (1) Tribbles amplification and overexpression; (2) the clinical significance of Tribbles overexpression; (3) upstream Tribbles gene and protein expression regulation; (4) Tribbles pharmacological modulation; (5) genetic modulation of Tribbles; and (6) downstream mechanisms regulated by Tribbles; establishing a comprehensive timeline, essential to better consolidate the current knowledge of Tribbles’ role in colorectal cancer.

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Synchronous global assessment of gene and protein expression in colorectal cancer progression

Genomics ◽

10.1016/j.ygeno.2005.03.012 ◽

2005 ◽

Vol 86 (2) ◽

pp. 142-158 ◽

Cited By ~ 37

Author(s):

K KWONG ◽

G BLOOM ◽

I YANG ◽

D BOULWARE ◽

D COPPOLA ◽

...

Keyword(s):

Colorectal Cancer ◽

Protein Expression ◽

Cancer Progression ◽

Global Assessment ◽

Gene And Protein Expression ◽

Colorectal Cancer Progression

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SEMA6B Overexpression Predicts Poor Prognosis and Correlates With the Tumor Immunosuppressive Microenvironment in Colorectal Cancer

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.687319 ◽

2021 ◽

Vol 8 ◽

Author(s):

Tiegang Li ◽

Zheng Yan ◽

Weiqi Wang ◽

Rixin Zhang ◽

Wenqiang Gan ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Colon Cancer ◽

T Cells ◽

Protein Expression ◽

Prognostic Biomarker ◽

Functional Enrichment ◽

Mrna Levels ◽

Gene And Protein Expression ◽

Immunosuppressive Microenvironment

Background: Semaphorin 6b (SEMA6B) is a member of the semaphorin axon-guidance family and has been demonstrated to both induce and inhibit tumor progression. However, the role of SEMA6B in colorectal cancer (CRC) has remained unclear. This study sought to explore the promising prognostic biomarker for CRC and to understand the expression pattern, clinical significance, immune effects, and biological functions of SEMA6B.Methods: SEMA6B expression in CRC was evaluated via multiple gene and protein expression databases and we identified its prognostic value through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Correlations between SEMA6B expression and components of the tumor immune microenvironment were analyzed by packages implemented in R, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and Tumor-Immune System Interactions database (TISIDB). RNA interference was performed to silence the expression of SEMA6B to explore its biological roles in the colon cancer cell lines HCT116 and LoVo.Results: The messenger RNA (mRNA) level of SEMA6B and the protein expression were higher in CRC tissues than adjacent normal tissues from multiple CRC datasets. High SEMA6B expression was significantly associated with dismal survival. Multivariate Cox regression analysis demonstrated that SEMA6B was an independent prognostic factor for progression-free survival (PFS). The nomogram showed a favorable predictive ability in PFS. Functional enrichment analysis and the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm revealed that the gene cluster associated with the high SEMA6B group were prominently involved in immune responses and inflammatory activities. Notably, SEMA6B expression was positively correlated with infiltrating levels of CD4+ T cells, macrophages, myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), neutrophils, and dendritic cells. Moreover, SEMA6B expression displayed strong correlations with diverse marker sets of immunosuppressive cells in CRC. Integrative analysis revealed that immunosuppressive molecules and immune checkpoints were markedly upregulated in CRC samples with high SEMA6B expression. Furthermore, knockdown of SMEA6B in colon cancer cells significantly inhibited cell proliferation, migration, invasion and reduced the mRNA levels of immunosuppressive molecules.Conclusion: Our findings provide evidence that high SEMA6B expression correlated with adverse prognosis and the tumor immunosuppressive microenvironment in CRC patients. Therefore, SEMA6B may serve as a novel prognostic biomarker for CRC, which offers further insights into developing CRC-targeted immunotherapies.

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Quantification of CK20 gene and protein expression in colorectal cancer by RT-PCR and immunohistochemistry reveals inter- and intratumour heterogeneity

The Journal of Pathology ◽

10.1002/path.1196 ◽

2002 ◽

Vol 198 (2) ◽

pp. 198-206 ◽

Cited By ~ 19

Author(s):

Silke Lassmann ◽

Markus Bauer ◽

Richie Soong ◽

Joachim Schreglmann ◽

Karim Tabiti ◽

...

Keyword(s):

Colorectal Cancer ◽

Protein Expression ◽

Rt Pcr ◽

Intratumour Heterogeneity ◽

Gene And Protein Expression

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Dihydropyrimidine Dehydrogenase Levels in Colorectal Cancer Cells Treated with a Combination of Heat Shock Protein 90 Inhibitor and Oxaliplatin or Capecitabine

Advanced Pharmaceutical Bulletin ◽

10.15171/apb.2019.052 ◽

2019 ◽

Vol 9 (3) ◽

pp. 439-444 ◽

Cited By ~ 1

Author(s):

Mahshid Mohammadian ◽

Shima Zeynali-Moghaddam ◽

Mohammad Hassan Khadem Ansari ◽

Yousef Rasmi ◽

Anahita Fathi Azarbayjani ◽

...

Keyword(s):

Colorectal Cancer ◽

Protein Expression ◽

Cell Lines ◽

Dihydropyrimidine Dehydrogenase ◽

Heat Shock Protein 90 ◽

Water Soluble ◽

Chemotherapy Response ◽

Expression Levels ◽

Protein Levels ◽

Gene And Protein Expression

Purpose: Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme in the catabolism of fluoropyrimidine drugs including capecitabine. A recent report has suggested that oxaliplatin chemotherapy is associated with elevated DPD levels and chemoresistance pattern. As a newly developed chemotherapeutic agent, 17-allyloamino-17-demethoxy-geldanamycin (17-AAG) can be effective in combination therapy with oxaliplatin and capecitabine in colorectal cancer (CRC). DPD expression level can be a predictive factor in oxaliplatin and capecitabine-based chemotherapy. We evaluated DPD in mRNA and protein levels with new treatments: 17-AAG in combination with oxaliplatin and capecitabine in HT-29 and HCT-116 cell lines. Methods: Drug sensitivity was determined by the water-soluble tetrazolium-1 assay in a previous survey. Then, we evaluated the expression levels of DPD and its relationship with the chemotherapy response in capecitabine, oxaliplatin, and 17-AAG treated cases in single and combination cases in two panels of CRC cell lines. DPD gene and protein expression levels were determined by real-time polymerase chain reaction and western blotting assay, respectively. Results: DPD gene expression levels insignificantly increased in single-treated cases versus untreated controls in both cell lines versus controls. Then, the capecitabine and oxaliplatin were added in double combinations, where DPD gene and protein expression increased in combination cases compared to pre-chemotherapy and single drug treatments. Conclusion: The elevated levels of cytotoxicity in more effective combinations could be related to a different mechanism apart from DPD mediating effects or high DPD level in the remaining resistance cells (drug-insensitive cells), which should be investigated in subsequent studies.

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