Associations of SEMA7A, SEMA4D, ADAMTS10, and ADAM8 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, Microsatellite Instability Status, and Cytokine Expression in Colorectal Cancer Tissue

被引:2
作者
Ochman, Blazej [1 ]
Limanowka, Piotr [1 ]
Mielcarska, Sylwia [1 ]
Kula, Agnieszka [2 ]
Dawidowicz, Miriam [2 ]
Wagner, Wiktor [1 ]
Hudy, Dorota [1 ]
Szrot, Monika [3 ]
Piecuch, Jerzy Zbigniew [3 ]
Piecuch, Jerzy [3 ]
Czuba, Zenon [4 ]
Swietochowska, Elzbieta [1 ]
机构
[1] Med Univ Silesia, Fac Med Sci Zabrze, Dept Med & Mol Biol, 19 Jordana, PL-41808 Zabrze, Poland
[2] Med Univ Silesia, Fac Med Sci Zabrze, Dept Oncol Surg, PL-41808 Katowice, Poland
[3] Med Univ Silesia, Fac Med Sci Zabrze, Dept Gen & Bariatr Surg & Emergency Med Zabrze, 10 Marii Curie Sklodowskiej, PL-41800 Zabrze, Poland
[4] Med Univ Silesia, Fac Med Sci Zabrze, Dept Microbiol & Immunol, 19 Jordana, PL-41808 Zabrze, Poland
关键词
semaphorin 7A (SEMA7A); ADAM (a disintegrin and metalloprotease) proteins; ADAMTS10; ADAM8; SEMA4D; colorectal cancer (CRC); microenvironment; tumor; K-ras oncogene; proto-oncogene proteins B-raf (BRAF); instability; microsatellite; SEMAPHORIN; 7A; THERAPEUTIC TARGET; TUMOR PROGRESSION; PROGNOSTIC ROLE; LUNG-CANCER; GROWTH; 4D; ANGIOGENESIS; CONTRIBUTES; METASTASIS;
D O I
10.3390/cimb46090609
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Semaphorins (SEMAs), ADAM, and ADAMTS family members are implicated in various cancer progression events within the tumor microenvironment across different cancers. In this study, we aimed to evaluate the expression of SEMA7A, SEMA4D, ADAM8, and ADAMTS10 in colorectal cancer (CRC) in relation to the mutational landscape of KRAS, NRAS, BRAF, PIK3CA, and AKT genes, microsatellite instability (MSI) status, and clinicopathological features. We also examined the associations between the expression of these proteins and selected cytokines, chemokines, and growth factors, assessed using a multiplex assay. Protein concentrations were quantified using ELISA in CRC tumors and tumor-free surgical margin tissue homogenates. Gene mutations were evaluated via RT-PCR, and MSI status was determined using immunohistochemistry (IHC). GSEA and statistical analyses were performed using R Studio. We observed a significantly elevated expression of SEMA7A in BRAF-mutant CRC tumors and an overexpression of ADAM8 in KRAS 12/13-mutant tumors. The expression of ADAMTS10 was decreased in PIK3CA-mutant CRC tumors. No significant differences in the expression of the examined proteins were observed based on MSI status. The SEMA7A and SEMA4D expressions were correlated with the expression of numerous cytokines associated with various immune processes. The potential immunomodulatory functions of these molecules and their suitability as therapeutic targets require further investigation.
引用
收藏
页码:10218 / 10248
页数:31
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