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

Carolina Hager Ribeiro, Karina Kramm, Felipe Gálvez-Jirón, Víctor Pola, Marco Bustamante, Hector R. Contreras, Andrea Sabag, Macarena Garrido-Tapia, Carolina J. Hernández, Roberto Zúñiga, Norberto Collazo, Pablo Hernán Sotelo, Camila Morales, Luis Mercado, Diego Catalán, Juan Carlos Aguillón, María Carmen Molina

Resultado de la investigación: Article

11 Citas (Scopus)

Resumen

Gastric cancer (GC) is the third most common cause of cancer death worldwide. Natural killer cells play an important role in the immune defense against transformed cells. They express the activating receptor NKG2D, whose ligands belong to the MIC and ULBP/RAET family. Although it is well established that these ligands are generally expressed in tumors, the association between their expression in the tumor and gastric mucosa and clinical parameters and prognosis of GC remains to be addressed. In the present study, MICA and MICB expression was analyzed, by flow cytometry, in 23 and 20 pairs of gastric tumor and adjacent non-neoplasic gastric mucosa, respectively. Additionally, ligands expression in 13 tumors and 7 gastric mucosa samples from GC patients were evaluated by immunohistochemistry. The mRNA levels of MICA in 9 pairs of tumor and mucosa were determined by quantitative PCR. Data were associated with the clinicopathological characteristics and the patient outcome. MICA expression was observed in 57% of tumors (13/23) and 44% of mucosal samples (10/23), while MICB was detected in 50% of tumors (10/20) and 45% of mucosal tissues (9/20). At the protein level, ligand expression was significantly higher in the tumor than in the gastric mucosa. MICA mRNA levels were also increased in the tumor as compared to the mucosa. However, clinicopathological analysis indicated that, in patients with tumors >5 cm, the expression of MICA and MICB in the tumor did not differ from that of the mucosa, and tumors >5 cm showed significantly higher MICA and MICB expression than tumors ≤5 cm. Patients presenting tumors >5 cm that expressed MICA and MICB had substantially shorter survival than those with large tumors that did not express these ligands. Our results suggest that locally sustained expression of MICA and MICB in the tumor may contribute to the malignant progression of GC and that expression of these ligands predicts an unfavorable prognosis in GC patients presenting large tumors.

Idioma originalEnglish
Páginas (desde-hasta)1309-1317
Número de páginas9
PublicaciónOncology Reports
Volumen35
N.º3
DOI
EstadoPublished - 1 mar 2016
Publicado de forma externa

Huella dactilar

Major Histocompatibility Complex
Stomach Neoplasms
Neoplasms
Gastric Mucosa
Ligands
Mucous Membrane
NK Cell Lectin-Like Receptor Subfamily K
Messenger RNA
Natural Killer Cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Medicine(all)

Citar esto

Ribeiro, C. H., Kramm, K., Gálvez-Jirón, F., Pola, V., Bustamante, M., Contreras, H. R., ... Molina, M. C. (2016). Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients. Oncology Reports, 35(3), 1309-1317. https://doi.org/10.3892/or.2015.4510
Ribeiro, Carolina Hager ; Kramm, Karina ; Gálvez-Jirón, Felipe ; Pola, Víctor ; Bustamante, Marco ; Contreras, Hector R. ; Sabag, Andrea ; Garrido-Tapia, Macarena ; Hernández, Carolina J. ; Zúñiga, Roberto ; Collazo, Norberto ; Sotelo, Pablo Hernán ; Morales, Camila ; Mercado, Luis ; Catalán, Diego ; Aguillón, Juan Carlos ; Molina, María Carmen. / Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients. En: Oncology Reports. 2016 ; Vol. 35, N.º 3. pp. 1309-1317.
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title = "Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients",
abstract = "Gastric cancer (GC) is the third most common cause of cancer death worldwide. Natural killer cells play an important role in the immune defense against transformed cells. They express the activating receptor NKG2D, whose ligands belong to the MIC and ULBP/RAET family. Although it is well established that these ligands are generally expressed in tumors, the association between their expression in the tumor and gastric mucosa and clinical parameters and prognosis of GC remains to be addressed. In the present study, MICA and MICB expression was analyzed, by flow cytometry, in 23 and 20 pairs of gastric tumor and adjacent non-neoplasic gastric mucosa, respectively. Additionally, ligands expression in 13 tumors and 7 gastric mucosa samples from GC patients were evaluated by immunohistochemistry. The mRNA levels of MICA in 9 pairs of tumor and mucosa were determined by quantitative PCR. Data were associated with the clinicopathological characteristics and the patient outcome. MICA expression was observed in 57{\%} of tumors (13/23) and 44{\%} of mucosal samples (10/23), while MICB was detected in 50{\%} of tumors (10/20) and 45{\%} of mucosal tissues (9/20). At the protein level, ligand expression was significantly higher in the tumor than in the gastric mucosa. MICA mRNA levels were also increased in the tumor as compared to the mucosa. However, clinicopathological analysis indicated that, in patients with tumors >5 cm, the expression of MICA and MICB in the tumor did not differ from that of the mucosa, and tumors >5 cm showed significantly higher MICA and MICB expression than tumors ≤5 cm. Patients presenting tumors >5 cm that expressed MICA and MICB had substantially shorter survival than those with large tumors that did not express these ligands. Our results suggest that locally sustained expression of MICA and MICB in the tumor may contribute to the malignant progression of GC and that expression of these ligands predicts an unfavorable prognosis in GC patients presenting large tumors.",
keywords = "Gastric cancer, Immune evasion, Major histocompatibility complex class I-related chains A and B, Natural killer cells, NKG2D receptor",
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Ribeiro, CH, Kramm, K, Gálvez-Jirón, F, Pola, V, Bustamante, M, Contreras, HR, Sabag, A, Garrido-Tapia, M, Hernández, CJ, Zúñiga, R, Collazo, N, Sotelo, PH, Morales, C, Mercado, L, Catalán, D, Aguillón, JC & Molina, MC 2016, 'Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients', Oncology Reports, vol. 35, n.º 3, pp. 1309-1317. https://doi.org/10.3892/or.2015.4510

Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients. / Ribeiro, Carolina Hager; Kramm, Karina; Gálvez-Jirón, Felipe; Pola, Víctor; Bustamante, Marco; Contreras, Hector R.; Sabag, Andrea; Garrido-Tapia, Macarena; Hernández, Carolina J.; Zúñiga, Roberto; Collazo, Norberto; Sotelo, Pablo Hernán; Morales, Camila; Mercado, Luis; Catalán, Diego; Aguillón, Juan Carlos; Molina, María Carmen.

En: Oncology Reports, Vol. 35, N.º 3, 01.03.2016, p. 1309-1317.

Resultado de la investigación: Article

TY - JOUR

T1 - Clinical significance of tumor expression of major histocompatibility complex class I-related chains A and B (MICA/B) in gastric cancer patients

AU - Ribeiro, Carolina Hager

AU - Kramm, Karina

AU - Gálvez-Jirón, Felipe

AU - Pola, Víctor

AU - Bustamante, Marco

AU - Contreras, Hector R.

AU - Sabag, Andrea

AU - Garrido-Tapia, Macarena

AU - Hernández, Carolina J.

AU - Zúñiga, Roberto

AU - Collazo, Norberto

AU - Sotelo, Pablo Hernán

AU - Morales, Camila

AU - Mercado, Luis

AU - Catalán, Diego

AU - Aguillón, Juan Carlos

AU - Molina, María Carmen

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Gastric cancer (GC) is the third most common cause of cancer death worldwide. Natural killer cells play an important role in the immune defense against transformed cells. They express the activating receptor NKG2D, whose ligands belong to the MIC and ULBP/RAET family. Although it is well established that these ligands are generally expressed in tumors, the association between their expression in the tumor and gastric mucosa and clinical parameters and prognosis of GC remains to be addressed. In the present study, MICA and MICB expression was analyzed, by flow cytometry, in 23 and 20 pairs of gastric tumor and adjacent non-neoplasic gastric mucosa, respectively. Additionally, ligands expression in 13 tumors and 7 gastric mucosa samples from GC patients were evaluated by immunohistochemistry. The mRNA levels of MICA in 9 pairs of tumor and mucosa were determined by quantitative PCR. Data were associated with the clinicopathological characteristics and the patient outcome. MICA expression was observed in 57% of tumors (13/23) and 44% of mucosal samples (10/23), while MICB was detected in 50% of tumors (10/20) and 45% of mucosal tissues (9/20). At the protein level, ligand expression was significantly higher in the tumor than in the gastric mucosa. MICA mRNA levels were also increased in the tumor as compared to the mucosa. However, clinicopathological analysis indicated that, in patients with tumors >5 cm, the expression of MICA and MICB in the tumor did not differ from that of the mucosa, and tumors >5 cm showed significantly higher MICA and MICB expression than tumors ≤5 cm. Patients presenting tumors >5 cm that expressed MICA and MICB had substantially shorter survival than those with large tumors that did not express these ligands. Our results suggest that locally sustained expression of MICA and MICB in the tumor may contribute to the malignant progression of GC and that expression of these ligands predicts an unfavorable prognosis in GC patients presenting large tumors.

AB - Gastric cancer (GC) is the third most common cause of cancer death worldwide. Natural killer cells play an important role in the immune defense against transformed cells. They express the activating receptor NKG2D, whose ligands belong to the MIC and ULBP/RAET family. Although it is well established that these ligands are generally expressed in tumors, the association between their expression in the tumor and gastric mucosa and clinical parameters and prognosis of GC remains to be addressed. In the present study, MICA and MICB expression was analyzed, by flow cytometry, in 23 and 20 pairs of gastric tumor and adjacent non-neoplasic gastric mucosa, respectively. Additionally, ligands expression in 13 tumors and 7 gastric mucosa samples from GC patients were evaluated by immunohistochemistry. The mRNA levels of MICA in 9 pairs of tumor and mucosa were determined by quantitative PCR. Data were associated with the clinicopathological characteristics and the patient outcome. MICA expression was observed in 57% of tumors (13/23) and 44% of mucosal samples (10/23), while MICB was detected in 50% of tumors (10/20) and 45% of mucosal tissues (9/20). At the protein level, ligand expression was significantly higher in the tumor than in the gastric mucosa. MICA mRNA levels were also increased in the tumor as compared to the mucosa. However, clinicopathological analysis indicated that, in patients with tumors >5 cm, the expression of MICA and MICB in the tumor did not differ from that of the mucosa, and tumors >5 cm showed significantly higher MICA and MICB expression than tumors ≤5 cm. Patients presenting tumors >5 cm that expressed MICA and MICB had substantially shorter survival than those with large tumors that did not express these ligands. Our results suggest that locally sustained expression of MICA and MICB in the tumor may contribute to the malignant progression of GC and that expression of these ligands predicts an unfavorable prognosis in GC patients presenting large tumors.

KW - Gastric cancer

KW - Immune evasion

KW - Major histocompatibility complex class I-related chains A and B

KW - Natural killer cells

KW - NKG2D receptor

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U2 - 10.3892/or.2015.4510

DO - 10.3892/or.2015.4510

M3 - Article

C2 - 26708143

AN - SCOPUS:84955448500

VL - 35

SP - 1309

EP - 1317

JO - Oncology Reports

JF - Oncology Reports

SN - 1021-335X

IS - 3

ER -