Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients

Ribeiro, Carolina; Kramm, Karina; Gálvez‐Jirón, Felipe; Pola, V; Bustamante, Marco; Contreras, Héctor R.; Sabag, Andrea; Garrido‐Tapia, Macarena; Hernández, Carolina; Zúñiga, Roberto Ariel Abeldaño; Collazo, Norberto; Sotelo, Pablo H.; Morales, Cristián; Mercado, Luís; Catalán, Diego; Aguillón, Juan Carlos; Molina, Marı́a

doi:10.3892/or.2015.4510

Cited by 26 publications

(15 citation statements)

References 48 publications

(70 reference statements)

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“…The expression of MHC class I in carcinoma cells may induce cytotoxic effects of lymphocytes and other immune cells (27,28). Carcinoma cells that do not express MHC class I may evade from the cytotoxic effects of immune cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of protein disulfide isomerase�A3 and its clinicopathological association in gastric cancer

et al. 2019

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Protein disulfide isomerase A3 (PDIA3) is a chaperone protein that supports the folding and processing of synthesized proteins. Its expression is associated with the prognosis of laryngeal cancer, hepatocellular carcinoma, diffuse glioma and uterine cervical cancer. In the present study, the expression levels of PDIA3 and its clinicopathological association were examined in 52 cases of gastric cancer (GC). The expression of PDIA3 was examined by immunohistochemistry and scored using a semi-quantitative method. According to the score, GC samples were classified into PDIA3-High and PDIA3-Low GC. PDIA3-High GC samples were predominantly of the intestinal type. Multivariate survival analysis indicated that PDIA3 expression and cancer stage were independent factors. The overall survival of PDIA3-High GC cases was significantly favorable compared with that of PDIA3-Low GC cases, and this was more evident in cases at an advanced stage. In GC cell cultures, the PDIA3 and major histocompatibility complex (MHC) class I proteins were expressed in three out of the four assessed cell lines according to western blot analysis. Notably, the expression of MHC class I was increased by the stimulation of interferon γ. Co-immunoprecipitation assays suggested the formation of a PDIA3 and MHC class I complex. The findings suggested that PDIA3 may be involved in the immune response of carcinoma cells. The improved prognosis in PDIA3-High GC may be accounted for, in part, by sufficient antigen processing and expression of MHC class I, which can be mediated by PDIA3. It was suggested that PDIA3 serves an important role in the pathobiology of GC, and that PDIA3 is a useful marker for the prediction of prognosis.

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Section: Discussionmentioning

confidence: 99%

Expression of protein disulfide isomerase�A3 and its clinicopathological association in gastric cancer

et al. 2019

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“…Furthermore, these two pathways were significantly enriched with major histocompatibility complex (MHC), class II, DRβ5 (HLA-DRB5), MHC class II, DMα (HLA-DMA), MHC class II, DQα1 (HLA-DQA1), and MHC class II, DRα (HLA-DRA), which encode important MHC class II molecules on antigen-presenting cells. Ribeiro et al found that the expression of MHC class I-related chains A and B in tumors may be involved in the progression of GC and be of predictive value for prognosis in GC with large tumors ( 32 ). This suggested that HLA-DRB5, HLA-DMA, HLA-DQA1 and HLA-DRA may be of predictive value for survival rates of patients with GC.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of microsatellite instability‑associated pathways and genes in gastric cancer

Hang

Wang

et al. 2018

Int J Mol Med

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The aim of the present study was to reveal the potential molecular mechanisms of microsatellite instability (MSI) on the prognosis of gastric cancer (GC). The investigation was performed based on an RNAseq expression profiling dataset downloaded from The Cancer Genome Atlas, including 64 high-level MSI (MSI-H) GC samples, 44 low-level MSI (MSI-L) GC samples and 187 stable microsatellite (MSI-S) GC samples. Differentially expressed genes (DEGs) were identified between the MSI-H, MSI-L and MSI-S samples. Pathway enrichment analysis was performed for the identified DEGs and the pathway deviation scores of the significant enrichment pathways were calculated. A Multi-Layer Perceptron (MLP) classifier, based on the different pathways associated with the MSI statuses was constructed for predicting the outcome of patients with GC, which was validated in another independent dataset. A total of 190 DEGs were selected between the MSI-H, MSI-L and MSI-S samples. The MLP classifier was established based on the deviation scores of 10 significant pathways, among which antigen processing and presentation, and inflammatory bowel disease pathways were significantly enriched with HLA-DRB5, HLA-DMA, HLA-DQA1 and HLA-DRA; the measles, toxoplasmosis and herpes simplex infection pathways were significantly enriched with Janus kinase 2 (JAK2), caspase-8 (CASP8) and Fas. The classifier performed well on an independent validation set with 100 GC samples. Taken together, the results indicated that MSI status may affect GC prognosis, partly through the antigen processing and presentation, inflammatory bowel disease, measles, toxoplasmosis and herpes simplex infection pathways. HLA-DRB5, HLA-DMA, HLA-DQA1, HLA-DRA, JAK2, CASP8 and Fas may be predictive factors for prognosis in GC.

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“…The expression of MICA and MICB proteins has been reported for many tumour types, with high expression associated with poor prognosis ( Spear et al , 2013 ). In contrast expression of MICA and MICB has been reported to be restricted to only a few normal tissue types, including gastrointestinal tract epithelium ( Groh et al , 1996 ; Allegretti et al , 2013 ), and adjacent normal mucosa from gastric cancer patients ( Ribeiro et al , 2015 ). MICA/B is also reported to be shed from the surface of cancer cells ( Salih et al , 2008 ; Zhang et al , 2015 ).…”

Section: Discussionmentioning

confidence: 99%

MHC class I chain-related protein A and B (MICA and MICB) are predominantly expressed intracellularly in tumour and normal tissue

Ghadially¹,

Brown²,

Lloyd³

et al. 2017

Br J Cancer

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Background:Major histocompatibility complex (MHC) class I chain-related protein A (MICA) and MHC class I chain-related protein B (MICB) are polymorphic proteins that are induced upon stress, damage or transformation of cells which act as a ‘kill me' signal through the natural-killer group 2, member D receptor expressed on cytotoxic lymphocytes. MICA/B are not thought to be constitutively expressed by healthy normal cells but expression has been reported for most tumour types. However, it is not clear how much of this protein is expressed on the cell surface.Methods:Using a novel, well-characterised antibody and both standard and confocal microscopy, we systematically profiled MICA/B expression in multiple human tumour and normal tissue.Results:High expression of MICA/B was detected in the majority of tumour tissues from multiple indications. Importantly, MICA/B proteins were predominantly localised intracellularly with only occasional evidence of cell membrane localisation. MICA/B expression was also demonstrated in most normal tissue epithelia and predominantly localised intracellularly. Crucially, we did not observe qualitative differences in cell surface expression between tumour and MICA/B expressing normal epithelia.Conclusions:This demonstrates for the first time that MICA/B is more broadly expressed in normal tissue and that expression is mainly intracellular with only a small fraction appearing on the cell surface of some epithelia and tumour cells.

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Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients

Cited by 26 publications

References 48 publications

Expression of protein disulfide isomerase�A3 and its clinicopathological association in gastric cancer

Expression of protein disulfide isomerase�A3 and its clinicopathological association in gastric cancer

Prognostic significance of microsatellite instability‑associated pathways and genes in gastric cancer

MHC class I chain-related protein A and B (MICA and MICB) are predominantly expressed intracellularly in tumour and normal tissue

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