Id-1, Id-2, and Id-3co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy

Carregando...
Imagem de Miniatura
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2016
Título da Revista
ISSN da Revista
Título do Volume
Editora
SAGE PUBLICATIONS LTD
Citação
EXPERIMENTAL BIOLOGY AND MEDICINE, v.241, n.11, p.1159-1168, 2016
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Inhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC.
Palavras-chave
Lung adenocarcinoma, inhibitors of DNA binding/inhibitors of differentiation, angiogenesis, immunohistochemistry, morphometry, prognosis
Referências
  1. BARONE MV, 1994, P NATL ACAD SCI USA, V91, P4985, DOI 10.1073/pnas.91.11.4985
  2. Benezra R, 2001, ONCOGENE, V20, P8334, DOI 10.1038/sj.onc.1205160
  3. Bhattacharya R, 2010, J ONCOL, V2010
  4. Chan ASW, 2003, ONCOGENE, V22, P6946, DOI 10.1038/sj.onc.1206799
  5. Damdinsuren B, 2005, INT J ONCOL, V26, P319
  6. de Sa VK, 2013, BRAZ J MED BIOL RES, V46, P21, DOI 10.1590/1414-431X20122263
  7. de Sa VK, 2012, HUM PATHOL, V43, P675, DOI 10.1016/j.humpath.2011.06.010
  8. Desprez PY, 1998, MOL CELL BIOL, V18, P4577
  9. FOLKMAN J, 1990, J NATL CANCER I, V82, P4, DOI 10.1093/jnci/82.1.4
  10. Goldstraw P, 2007, J THORAC ONCOL, V2, P706, DOI 10.1097/JTO.0b013e31812f3c1a
  11. Gugger M, 2001, LUNG CANCER-J IASLC, V33, P229, DOI 10.1016/S0169-5002(01)00196-9
  12. Hasskarl J, 2002, CANCER BIOL THER, V1, P91
  13. Irigoyen M, 2010, MOL CANCER, V9, DOI 10.1186/1476-4598-9-130
  14. Jang KS, 2006, CANCER LETT, V244, P203, DOI 10.1016/j.canlet.2005.12.016
  15. Jang TJ, 2006, INT J CANCER, V118, P1356, DOI 10.1002/ijc.21503
  16. Kadota K, 2015, J THORAC ONCOL, V10, P806, DOI 10.1097/JTO.0000000000000486
  17. Kamalian L, 2008, CLIN CANCER RES, V14, P2318, DOI 10.1158/1078-0432.CCR-07-4716
  18. Lyden D, 1999, NATURE, V401, P670, DOI 10.1038/44334
  19. Maruyama H, 1999, AM J PATHOL, V155, P815, DOI 10.1016/S0002-9440(10)65180-2
  20. Maw MK, 2008, BRIT J CANCER, V99, P1557, DOI 10.1038/sj.bjc.6604722
  21. MCCARTY KS, 1985, ARCH PATHOL LAB MED, V109, P716
  22. Norton JD, 1998, TRENDS CELL BIOL, V8, P58, DOI 10.1016/S0962-8924(97)01183-5
  23. Norton JD, 1998, MOL CELL BIOL, V18, P2371
  24. Perk J, 2005, NAT REV CANCER, V5, P603, DOI 10.1038/nrc1673
  25. Perk J, 2006, CANCER RES, V66, P10870, DOI 10.1158/0008-5472.CAN-06-2643
  26. Ponz-Sarvise M, 2011, CLIN CANCER RES, V17, P4155, DOI 10.1158/1078-0432.CCR-10-3381
  27. Ratto GB, 2009, J THORAC CARDIOV SUR, V138, P849, DOI 10.1016/j.jtcvs.2009.03.017
  28. RIECHMANN V, 1995, CELL GROWTH DIFFER, V6, P837
  29. RIECHMANN V, 1994, NUCLEIC ACIDS RES, V22, P749, DOI 10.1093/nar/22.5.749
  30. Riquet Marc, 2007, Ann Thorac Surg, V84, P1818, DOI 10.1016/j.athoracsur.2007.07.015
  31. Rothschild SI, 2011, LUNG CANCER, V71, P306, DOI 10.1016/j.lungcan.2010.06.018
  32. Rush WR, 2009, J THORAC ONCOL, V4, P568
  33. Sica G, 2010, AM J SURG PATHOL, V34, P1155, DOI 10.1097/PAS.0b013e3181e4ee32
  34. Sikder HA, 2003, CANCER CELL, V3, P525, DOI 10.1016/S1535-6108(03)00141-7
  35. Song XB, 2011, ACTA BIOCH BIOPH SIN, V43, P796, DOI 10.1093/abbs/gmr074
  36. Souza P, 2010, HUM PATHOL, V41, P239, DOI 10.1016/j.humpath.2009.07.018
  37. Su Y, 2013, J TRANSL MED, V29, P132
  38. Tsuchiya T, 2005, CANCER SCI, V96, P784, DOI 10.1111/j.1349-7006.2005.0113.x
  39. Umetani N, 2004, CLIN CANCER RES, V10, P7475, DOI 10.1158/1078-0432.CCR-04-0689
  40. Wilson JW, 2001, CANCER RES, V61, P8803
  41. Yang HY, 2010, ONCOL REP, V23, P321, DOI 10.3892/or_00000639
  42. Yu L, 2013, GYNECOL ONCOL, V128, P391, DOI 10.1016/j.ygyno.2012.11.002
  43. Yu XL, 2009, PATHOL ONCOL RES, V15, P91, DOI 10.1007/s12253-008-9096-y
  44. Yuen HF, 2007, BRIT J CANCER, V97, P1409, DOI 10.1038/sj.bjc.6604035
  45. Yuen HF, 2006, MODERN PATHOL, V19, P931, DOI 10.1038/modpathol.3800602