Prognostic role of XTP1/DEPDC1B and SDP35/DEPDC1A in high grade soft-tissue sarcomas

Serena Pollino, Maria Serena Benassi, Laura Pazzaglia, Amalia Conti, Nicoletta Bertani, Alberto Righi, Martina Piccinni Leopardi, Piero Picci, Roberto Perris

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background. The outcome of patients with metastatic soft tissue sarcoma (STS) remains unfavourable and new therapeutic strategies are needed. The aim of this study was to determine the role of RhoGAP, XTP1/DEPDC1B and SDP35/DEPDC1A, as possible prognostic markers, to be used to identify candidate patients for more effective and personalized therapies. Materials-Methods. SDP35/DEPDC1A and XTP1/ DEPDC1B transcriptional levels were evaluated by Real-Time PCR in 86 primary STS and 22 paired lung metastasis. 17 normal tissues were used as control. Protein expression was evaluated by tissue microarray, including 152 paraffin-embedded STS samples and by western blot in 22 lung metastases and paired primary STS. Non-parametric and parametric analysis were used to establish the differences in gene and protein expression and prognostic factors were tested with Kaplan Meier and Cox’s regression analyses. Results. SDP35/DEPDC1A and XTP1/DEPDC1B gene were down-regulated in adjacent normal tissues while sarcoma specimens presented high mRNA levels, significantly related to metastasis-free survival. Gene expression further increased in paired metastatic lesions. Immunohistochemical staining showed a variable expression in intensity and distribution, with a significantly higher probability of metastatic disease in patients up-regulating SDP35/DEPDC1A. Western blotting assessed high levels of proteins in STS specimens and indicated a stronger expression of SDP35/DEPDC1A in metastases when compared to primary tumours. Multivariate analyses highlighted that SDP35/DEPDC1A abundance, grade III and no history of radiation therapy were significant independent risk factors. Conclusions. Our results demonstrated that increased expression of SDP35/DEPDC1A and XPT1/DEPDC1B correlates with metastatic progression and identified SDP35/DEPDC1A as an independent marker for prediction of poor prognosis.

Original languageEnglish
Pages (from-to)597-608
Number of pages12
JournalHistology and Histopathology
Volume33
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Sarcoma
Neoplasm Metastasis
Western Blotting
Gene Expression
Lung
Proteins
Paraffin
Real-Time Polymerase Chain Reaction
Radiotherapy
Multivariate Analysis
Regression Analysis
Staining and Labeling
Messenger RNA
Survival
Therapeutics
Genes
Neoplasms

Keywords

  • Sarcoma
  • Metastasis
  • Gene and protein expression
  • Prognosis
  • Biomarkers

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Prognostic role of XTP1/DEPDC1B and SDP35/DEPDC1A in high grade soft-tissue sarcomas. / Pollino, Serena; Benassi, Maria Serena; Pazzaglia, Laura; Conti, Amalia; Bertani, Nicoletta; Righi, Alberto; Piccinni Leopardi, Martina; Picci, Piero; Perris, Roberto.

In: Histology and Histopathology, Vol. 33, No. 6, 01.06.2018, p. 597-608.

Research output: Contribution to journalArticle

Pollino, Serena ; Benassi, Maria Serena ; Pazzaglia, Laura ; Conti, Amalia ; Bertani, Nicoletta ; Righi, Alberto ; Piccinni Leopardi, Martina ; Picci, Piero ; Perris, Roberto. / Prognostic role of XTP1/DEPDC1B and SDP35/DEPDC1A in high grade soft-tissue sarcomas. In: Histology and Histopathology. 2018 ; Vol. 33, No. 6. pp. 597-608.
@article{19a83189258d43deb5e247cc644dff26,
title = "Prognostic role of XTP1/DEPDC1B and SDP35/DEPDC1A in high grade soft-tissue sarcomas",
abstract = "Background. The outcome of patients with metastatic soft tissue sarcoma (STS) remains unfavourable and new therapeutic strategies are needed. The aim of this study was to determine the role of RhoGAP, XTP1/DEPDC1B and SDP35/DEPDC1A, as possible prognostic markers, to be used to identify candidate patients for more effective and personalized therapies. Materials-Methods. SDP35/DEPDC1A and XTP1/ DEPDC1B transcriptional levels were evaluated by Real-Time PCR in 86 primary STS and 22 paired lung metastasis. 17 normal tissues were used as control. Protein expression was evaluated by tissue microarray, including 152 paraffin-embedded STS samples and by western blot in 22 lung metastases and paired primary STS. Non-parametric and parametric analysis were used to establish the differences in gene and protein expression and prognostic factors were tested with Kaplan Meier and Cox’s regression analyses. Results. SDP35/DEPDC1A and XTP1/DEPDC1B gene were down-regulated in adjacent normal tissues while sarcoma specimens presented high mRNA levels, significantly related to metastasis-free survival. Gene expression further increased in paired metastatic lesions. Immunohistochemical staining showed a variable expression in intensity and distribution, with a significantly higher probability of metastatic disease in patients up-regulating SDP35/DEPDC1A. Western blotting assessed high levels of proteins in STS specimens and indicated a stronger expression of SDP35/DEPDC1A in metastases when compared to primary tumours. Multivariate analyses highlighted that SDP35/DEPDC1A abundance, grade III and no history of radiation therapy were significant independent risk factors. Conclusions. Our results demonstrated that increased expression of SDP35/DEPDC1A and XPT1/DEPDC1B correlates with metastatic progression and identified SDP35/DEPDC1A as an independent marker for prediction of poor prognosis.",
keywords = "Sarcoma, Metastasis, Gene and protein expression, Prognosis, Biomarkers",
author = "Serena Pollino and Benassi, {Maria Serena} and Laura Pazzaglia and Amalia Conti and Nicoletta Bertani and Alberto Righi and {Piccinni Leopardi}, Martina and Piero Picci and Roberto Perris",
year = "2018",
month = "6",
day = "1",
doi = "10.14670/HH-11-959",
language = "English",
volume = "33",
pages = "597--608",
journal = "Histology and Histopathology",
issn = "0213-3911",
publisher = "Histology and Histopathology",
number = "6",

}

TY - JOUR

T1 - Prognostic role of XTP1/DEPDC1B and SDP35/DEPDC1A in high grade soft-tissue sarcomas

AU - Pollino, Serena

AU - Benassi, Maria Serena

AU - Pazzaglia, Laura

AU - Conti, Amalia

AU - Bertani, Nicoletta

AU - Righi, Alberto

AU - Piccinni Leopardi, Martina

AU - Picci, Piero

AU - Perris, Roberto

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background. The outcome of patients with metastatic soft tissue sarcoma (STS) remains unfavourable and new therapeutic strategies are needed. The aim of this study was to determine the role of RhoGAP, XTP1/DEPDC1B and SDP35/DEPDC1A, as possible prognostic markers, to be used to identify candidate patients for more effective and personalized therapies. Materials-Methods. SDP35/DEPDC1A and XTP1/ DEPDC1B transcriptional levels were evaluated by Real-Time PCR in 86 primary STS and 22 paired lung metastasis. 17 normal tissues were used as control. Protein expression was evaluated by tissue microarray, including 152 paraffin-embedded STS samples and by western blot in 22 lung metastases and paired primary STS. Non-parametric and parametric analysis were used to establish the differences in gene and protein expression and prognostic factors were tested with Kaplan Meier and Cox’s regression analyses. Results. SDP35/DEPDC1A and XTP1/DEPDC1B gene were down-regulated in adjacent normal tissues while sarcoma specimens presented high mRNA levels, significantly related to metastasis-free survival. Gene expression further increased in paired metastatic lesions. Immunohistochemical staining showed a variable expression in intensity and distribution, with a significantly higher probability of metastatic disease in patients up-regulating SDP35/DEPDC1A. Western blotting assessed high levels of proteins in STS specimens and indicated a stronger expression of SDP35/DEPDC1A in metastases when compared to primary tumours. Multivariate analyses highlighted that SDP35/DEPDC1A abundance, grade III and no history of radiation therapy were significant independent risk factors. Conclusions. Our results demonstrated that increased expression of SDP35/DEPDC1A and XPT1/DEPDC1B correlates with metastatic progression and identified SDP35/DEPDC1A as an independent marker for prediction of poor prognosis.

AB - Background. The outcome of patients with metastatic soft tissue sarcoma (STS) remains unfavourable and new therapeutic strategies are needed. The aim of this study was to determine the role of RhoGAP, XTP1/DEPDC1B and SDP35/DEPDC1A, as possible prognostic markers, to be used to identify candidate patients for more effective and personalized therapies. Materials-Methods. SDP35/DEPDC1A and XTP1/ DEPDC1B transcriptional levels were evaluated by Real-Time PCR in 86 primary STS and 22 paired lung metastasis. 17 normal tissues were used as control. Protein expression was evaluated by tissue microarray, including 152 paraffin-embedded STS samples and by western blot in 22 lung metastases and paired primary STS. Non-parametric and parametric analysis were used to establish the differences in gene and protein expression and prognostic factors were tested with Kaplan Meier and Cox’s regression analyses. Results. SDP35/DEPDC1A and XTP1/DEPDC1B gene were down-regulated in adjacent normal tissues while sarcoma specimens presented high mRNA levels, significantly related to metastasis-free survival. Gene expression further increased in paired metastatic lesions. Immunohistochemical staining showed a variable expression in intensity and distribution, with a significantly higher probability of metastatic disease in patients up-regulating SDP35/DEPDC1A. Western blotting assessed high levels of proteins in STS specimens and indicated a stronger expression of SDP35/DEPDC1A in metastases when compared to primary tumours. Multivariate analyses highlighted that SDP35/DEPDC1A abundance, grade III and no history of radiation therapy were significant independent risk factors. Conclusions. Our results demonstrated that increased expression of SDP35/DEPDC1A and XPT1/DEPDC1B correlates with metastatic progression and identified SDP35/DEPDC1A as an independent marker for prediction of poor prognosis.

KW - Sarcoma

KW - Metastasis

KW - Gene and protein expression

KW - Prognosis

KW - Biomarkers

UR - http://www.scopus.com/inward/record.url?scp=85044441678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044441678&partnerID=8YFLogxK

U2 - 10.14670/HH-11-959

DO - 10.14670/HH-11-959

M3 - Article

AN - SCOPUS:85044441678

VL - 33

SP - 597

EP - 608

JO - Histology and Histopathology

JF - Histology and Histopathology

SN - 0213-3911

IS - 6

ER -