The serine protease HtrA1 is a novel prognostic factor for human mesothelioma

Alfonso Baldi, Marcella Mottolese, Bruno Vincenzi, Mara Campioni, Pasquale Mellone, Mariapia Di Marino, Vincenzo G. di Crescenzo, Paolo Visca, Simona Menegozzo, Enrico P. Spugnini, Gennaro Citro, Anna Ceribelli, Alessandra Mirri, Jeremy Chien, Viji Shridhar, Michael Ehrmann, Mario Santini, Francesco Facciolo

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Aims: The objective of our study was to analyze the potential prognostic value of the expression of the serine protease HtrA1 and of EGFR in 70 malignant mesotheliomas. Materials & methods: Immunohistochemistry was used to determine the expression of HtrA1 and EGFR. Univariate and multivariate analyses were used to correlate expression of these molecular factors in combination with available clinicopathologic data to patient survival. Results: A positive, statistically significant relationship has been recorded between HtrA1 expression level and survival (p < 0.0001). By contrast, a negative relationship has been identified between EGFR expression and survival (p = 0.02). Moreover, extension of the tumor (T) and involvement of lymph nodes (N) advanced status (p = 0.001 and 0.002, respectively), as well as the sarcomatoid histotype (p = 0.005), correlated significantly with poor survival. Finally, by a multivariate Cox regression analysis, the only immunohistochemical parameter that resulted to influence overall survival was HtrA1 (p = 0.0001). Interestingly, the prognostic value of HtrA1 expression was completely independent from EGFR expression (p < 0.0001). Conclusion: This is the first study of the relationship between HtrA1 expression and survival of mesothelioma patients. The data obtained strongly indicate the utilization of HtrA1 expression as a prognostic parameter for mesothelioma and suggest this serine protease as a possible molecular target for the treatment of malignant mesotheliomas.

Original languageEnglish (US)
Pages (from-to)1069-1077
Number of pages9
JournalPharmacogenomics
Volume9
Issue number8
DOIs
StatePublished - Aug 29 2008
Externally publishedYes

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Mesothelioma
Serine Proteases
Survival
Multivariate Analysis
Lymph Nodes
Immunohistochemistry
Regression Analysis
Neoplasms

Keywords

  • EGFR
  • HtrA1
  • Immunohistochemistry
  • Mesothelioma
  • Prognosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Baldi, A., Mottolese, M., Vincenzi, B., Campioni, M., Mellone, P., Di Marino, M., ... Facciolo, F. (2008). The serine protease HtrA1 is a novel prognostic factor for human mesothelioma. Pharmacogenomics, 9(8), 1069-1077. https://doi.org/10.2217/14622416.9.8.1069

The serine protease HtrA1 is a novel prognostic factor for human mesothelioma. / Baldi, Alfonso; Mottolese, Marcella; Vincenzi, Bruno; Campioni, Mara; Mellone, Pasquale; Di Marino, Mariapia; di Crescenzo, Vincenzo G.; Visca, Paolo; Menegozzo, Simona; Spugnini, Enrico P.; Citro, Gennaro; Ceribelli, Anna; Mirri, Alessandra; Chien, Jeremy; Shridhar, Viji; Ehrmann, Michael; Santini, Mario; Facciolo, Francesco.

In: Pharmacogenomics, Vol. 9, No. 8, 29.08.2008, p. 1069-1077.

Research output: Contribution to journalArticle

Baldi, A, Mottolese, M, Vincenzi, B, Campioni, M, Mellone, P, Di Marino, M, di Crescenzo, VG, Visca, P, Menegozzo, S, Spugnini, EP, Citro, G, Ceribelli, A, Mirri, A, Chien, J, Shridhar, V, Ehrmann, M, Santini, M & Facciolo, F 2008, 'The serine protease HtrA1 is a novel prognostic factor for human mesothelioma', Pharmacogenomics, vol. 9, no. 8, pp. 1069-1077. https://doi.org/10.2217/14622416.9.8.1069
Baldi A, Mottolese M, Vincenzi B, Campioni M, Mellone P, Di Marino M et al. The serine protease HtrA1 is a novel prognostic factor for human mesothelioma. Pharmacogenomics. 2008 Aug 29;9(8):1069-1077. https://doi.org/10.2217/14622416.9.8.1069
Baldi, Alfonso ; Mottolese, Marcella ; Vincenzi, Bruno ; Campioni, Mara ; Mellone, Pasquale ; Di Marino, Mariapia ; di Crescenzo, Vincenzo G. ; Visca, Paolo ; Menegozzo, Simona ; Spugnini, Enrico P. ; Citro, Gennaro ; Ceribelli, Anna ; Mirri, Alessandra ; Chien, Jeremy ; Shridhar, Viji ; Ehrmann, Michael ; Santini, Mario ; Facciolo, Francesco. / The serine protease HtrA1 is a novel prognostic factor for human mesothelioma. In: Pharmacogenomics. 2008 ; Vol. 9, No. 8. pp. 1069-1077.
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AU - Mottolese, Marcella

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AU - Mellone, Pasquale

AU - Di Marino, Mariapia

AU - di Crescenzo, Vincenzo G.

AU - Visca, Paolo

AU - Menegozzo, Simona

AU - Spugnini, Enrico P.

AU - Citro, Gennaro

AU - Ceribelli, Anna

AU - Mirri, Alessandra

AU - Chien, Jeremy

AU - Shridhar, Viji

AU - Ehrmann, Michael

AU - Santini, Mario

AU - Facciolo, Francesco

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N2 - Aims: The objective of our study was to analyze the potential prognostic value of the expression of the serine protease HtrA1 and of EGFR in 70 malignant mesotheliomas. Materials & methods: Immunohistochemistry was used to determine the expression of HtrA1 and EGFR. Univariate and multivariate analyses were used to correlate expression of these molecular factors in combination with available clinicopathologic data to patient survival. Results: A positive, statistically significant relationship has been recorded between HtrA1 expression level and survival (p < 0.0001). By contrast, a negative relationship has been identified between EGFR expression and survival (p = 0.02). Moreover, extension of the tumor (T) and involvement of lymph nodes (N) advanced status (p = 0.001 and 0.002, respectively), as well as the sarcomatoid histotype (p = 0.005), correlated significantly with poor survival. Finally, by a multivariate Cox regression analysis, the only immunohistochemical parameter that resulted to influence overall survival was HtrA1 (p = 0.0001). Interestingly, the prognostic value of HtrA1 expression was completely independent from EGFR expression (p < 0.0001). Conclusion: This is the first study of the relationship between HtrA1 expression and survival of mesothelioma patients. The data obtained strongly indicate the utilization of HtrA1 expression as a prognostic parameter for mesothelioma and suggest this serine protease as a possible molecular target for the treatment of malignant mesotheliomas.

AB - Aims: The objective of our study was to analyze the potential prognostic value of the expression of the serine protease HtrA1 and of EGFR in 70 malignant mesotheliomas. Materials & methods: Immunohistochemistry was used to determine the expression of HtrA1 and EGFR. Univariate and multivariate analyses were used to correlate expression of these molecular factors in combination with available clinicopathologic data to patient survival. Results: A positive, statistically significant relationship has been recorded between HtrA1 expression level and survival (p < 0.0001). By contrast, a negative relationship has been identified between EGFR expression and survival (p = 0.02). Moreover, extension of the tumor (T) and involvement of lymph nodes (N) advanced status (p = 0.001 and 0.002, respectively), as well as the sarcomatoid histotype (p = 0.005), correlated significantly with poor survival. Finally, by a multivariate Cox regression analysis, the only immunohistochemical parameter that resulted to influence overall survival was HtrA1 (p = 0.0001). Interestingly, the prognostic value of HtrA1 expression was completely independent from EGFR expression (p < 0.0001). Conclusion: This is the first study of the relationship between HtrA1 expression and survival of mesothelioma patients. The data obtained strongly indicate the utilization of HtrA1 expression as a prognostic parameter for mesothelioma and suggest this serine protease as a possible molecular target for the treatment of malignant mesotheliomas.

KW - EGFR

KW - HtrA1

KW - Immunohistochemistry

KW - Mesothelioma

KW - Prognosis

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