Novel insights into transcriptional dysregulation in colorectal cancer

被引:11
|
作者
Feodorova, Y. [1 ]
Tashkova, D. [2 ]
Koev, I. [3 ]
Todorov, A. [4 ]
Kostov, G. [5 ,6 ]
Simitchiev, K. [7 ]
Belovejdov, V. [2 ]
Dimov, R. [5 ,6 ]
Sarafian, V. [1 ,8 ]
机构
[1] Med Univ Plovdiv, Dept Med Biol, Plovdiv, Bulgaria
[2] Med Univ Plovdiv, Dept Gen & Clin Pathol, Plovdiv, Bulgaria
[3] Univ Hosp Pulmed, Dept Neurosurg, Plovdiv, Bulgaria
[4] Med Univ Plovdiv, Dept Propedeut Surg Dis, Plovdiv, Bulgaria
[5] Med Univ Plovdiv, Dept Special Surg, Plovdiv, Bulgaria
[6] Univ Hosp Kaspela, Dept Surg, Plovdiv, Bulgaria
[7] Univ Plovdiv Paisii Hilendarski, Dept Analyt Chem & Comp Chem, Plovdiv, Bulgaria
[8] Technol Ctr Emergency Med, Plovdiv, Bulgaria
关键词
CRC; gene expression; GUCA2B; KRAS; GENE-EXPRESSION SIGNATURE; MESSENGER-RNA EXPRESSION; NECROSIS-FACTOR-ALPHA; COLON-CANCER; EGFR EXPRESSION; TNF-ALPHA; CYTOKINE PROFILES; RECTAL-CANCER; INTERLEUKIN-6; PROGNOSIS;
D O I
10.4149/neo_2018_170707N467
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Although CRC has been comprehensively characterized at the molecular level, the tumor heterogeneity hinders the identification of reliable diagnostic, prognostic and predictive biomarkers. Molecular stratification of CRC is based on prevalent gene mutations and transcription profiles but its significance for clinical practice remains obscure. Indeed, activating mutations in the genes KRAS, NRAS, and BRAF are the only predictive biomarkers for anti-EGFR antibody therapy routinely tested in the clinic for advanced stages of CRC. Gene expression signatures are important for clarifying the molecular mechanisms of CRC development and progression, but only two such tests for predicting recurrence risk are commercially available. The aim of our study was to propose a diagnostic approach based on mutation and gene expression analysis that can be routinely applied in the clinic for defining the most appropriate treatment strategy for each patient. We used qPCR to determine the presence of KRAS mutations and measure the transcription levels of a panel of 26 genes in 24 CRC patients. Statistical analyses were applied to check for associations between clinicopathological and molecular parameters. Our results reveal novel data concerning CRC carcinogenesis: almost universal downregulation of EGFR; differential role of the pro-inflammatory cytokines TNF-a and IL-6; overexpression of the vitamin B12 transporter transcobalamin 1; tumor-suppressor function of SETD2, CA7, and GUCA2B. The practical application of these findings has yet to be clarified.
引用
收藏
页码:415 / 424
页数:10
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