SLPI for Prostate Cancer

SLPI: a Novel Biomarker of Prostate Cancer

Exploratory study of SLPI expression in human prostate cancer patients This is a no-profit exploratory study about the expression of SLPI in human prostate cancer patients that will enroll about 200 patients admitted for suspect prostate cancer to Careggi University Hospital. We will verify whether an increase SLPI levels in the sera may serve as biomarker of cancer progression.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Prostatic Neoplasm
• Intervention / Treatment: Diagnostic test: Secretory leukocyte protease inhibitor (SLPI) in prostate cancer; Diagnostic test: Determination of molecular alterations; Diagnostic test: Secretory leukocyte protease inhibitor (SLPI) Healthy

Detailed Description

Prostate cancer (PC) is a heterogeneous disease that occurs more frequently in elderly men. Prostate cancer is usually localized and it has a slow progression; thus, the patient may not suffer from any symptom for years. However, a proportion of patients PC develops metastases and may become a clinically relevant disease that can show an aggressive behavior and, eventually, give metastases. In any event, since it is the most common male cancer in the Western countries, it is the second leading cause of cancer deaths in males. For this reason the identification of the molecular alterations determining the different clinical behaviors and of the associated biomarkers would be extremely useful.

The Secretory leukocyte protease inhibitor (SLPI) is a serine protease which best-defined function is to protect host tissues from the excessive damage by proteolytic enzymes released during inflammation. Recently SLPI has been found overexpressed in a variety of cancers (pancreatic, papillary thyroid, uterine cervix, endometrial, and ovarian cancer). In apparent contrast, SLPI has been found reduced in the sera (and tumor tissue) of prostate cancer patients in the respect of healthy subjects and of subjects with benign hyperplasia. However, SLPI has been found upregulated in castration resistant prostate cancer (CRPC) patients and in a subset of CRPC cell lines.

These data suggest that expression of SLPI in prostate cancer could be biphasic: underexpressed during the early stages and overexpressed during progression. This peculiar pattern of SLPI expression suggests that SLPI may play a role in prostate cancer pathogenesis and/or in determining its neoplastic features. In this respect, it is noteworthy that SLPI is located at 20q13.2 (HPC20 locus), a locus harboring prostate cancer susceptibility genes. Based on these data it is possible to hypothesize that prostate cancer progression could be associated, and possibly heralded, by the increase of SLPI.

This is an observational investigation of SLPI levels in blood and tissue samples of patients with prostate disease with the explorative goal to verify whether SLPI could be a potential biomarker of prostate cancer progression.

• Study Type: Observational
• Enrollment (Anticipated): 280

Contacts and Locations

• Study Contact: Name: Silvia Benemei; Phone Number: 055 7946999; Email: silvia.benemei@unifi.it

Study Locations

• Italy
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Recruiting
      • Careggi University Hospital
      • Contact: Sergio Serni, Prof; Email: sergio.serni@unifi.it
      • Sub-Investigator: Mauro Gacci, MD
      • Sub-Investigator: Simone Morselli, MD
      • Principal Investigator: Gabriella Nesi, Prof
      • Principal Investigator: Rosario Notaro, MD
      • Principal Investigator: Gianni Amunni, Prof
      • Principal Investigator: Maria De Angioletti, PhD
      • Sub-Investigator: Riccardo Campi, MD
      • Sub-Investigator: Rossella Nicoletti, MD
      • Sub-Investigator: Lorenzo Verdelli, MD
      • Sub-Investigator: Alessio Taddei, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

This study will be enroll patient with prostate carcinoma and, as control groups, patients with benign prostate hyperplasia (BPH) and males older than 50 years with neither prostate disease nor any other neoplasia.

Description

Inclusion Criteria:

• Patients with prostate carcinoma.
• Patients with Benign Prostatic Hyperplasia.
• Male subjects older that 50 years without prostate or neoplastic diseases.

Exclusion Criteria:

• Male subjects younger that 50 years without prostate disease.
• Male subjects with neoplastic diseases either than prostate.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case; 200 patients with a suspicion of prostate cancer	Diagnostic test: Secretory leukocyte protease inhibitor (SLPI) in prostate cancer; 7 ml of peripheral blood and a urine sample for the determination of SLPI concentration. Blood samples will be promptly processed to obtain sera; both sera and urine will be stored at -80°C in the laboratory. The levels of SLPI in the serum and in the urine will be quantitated by an ELISA assay by using the "Human SLPI Quantikine ELISA Kit". SLPI level will be measured at diagnosis and during the follow-up (3, 9, 15 months and in case of progression). Immunohistochemistry protocol for SLPI immunostaining to investigate SLPI levels prostate tissue; Diagnostic test: Determination of molecular alterations; The presence of ETS translocation (or of ETS overexpression) will be tested on bioptic samples in each patient as for routine diagnostic procedures. First, ERG overexpression will be investigated by ERG immunostaining. The samples negative for ERG immunostaining will be studied for TMPRSS2-ERG translocation either by in situ FISH or by a translocation-specific RT-PCR. Next, the biopsies negative for TMPRSS2-ERG will be tested for the overexpression of other ETS proteins (ETV1, ETV4, ETV5 and for others rarely occurring ETS). When possible, it will be determined the status of pTEN gene, the tumor suppressor most frequently lost in prostate patients. The patients negative for the overexpression of the ETS proteins will be tested for SPINK1.
Control A; (a) 50 patients with benign prostate hyperplasia (BPH)	Diagnostic test: Determination of molecular alterations; The presence of ETS translocation (or of ETS overexpression) will be tested on bioptic samples in each patient as for routine diagnostic procedures. First, ERG overexpression will be investigated by ERG immunostaining. The samples negative for ERG immunostaining will be studied for TMPRSS2-ERG translocation either by in situ FISH or by a translocation-specific RT-PCR. Next, the biopsies negative for TMPRSS2-ERG will be tested for the overexpression of other ETS proteins (ETV1, ETV4, ETV5 and for others rarely occurring ETS). When possible, it will be determined the status of pTEN gene, the tumor suppressor most frequently lost in prostate patients. The patients negative for the overexpression of the ETS proteins will be tested for SPINK1.; Diagnostic test: Secretory leukocyte protease inhibitor (SLPI) Healthy; SLPI level will be measured also in the serum and in the urine from controls (patients with BPH and healthy subjects). 7 ml of peripheral blood and a urine sample for the determination of SLPI concentration. Blood samples will be promptly processed to obtain sera; both sera and urine will be stored at -80°C in the laboratory. The levels of SLPI in the serum and in the urine will be quantitated by an ELISA assay by using the "Human SLPI Quantikine ELISA Kit".
Control B; (b) 30 male subjects older than 50 years with neither prostate disease nor any other neoplasia	Diagnostic test: Secretory leukocyte protease inhibitor (SLPI) Healthy; SLPI level will be measured also in the serum and in the urine from controls (patients with BPH and healthy subjects). 7 ml of peripheral blood and a urine sample for the determination of SLPI concentration. Blood samples will be promptly processed to obtain sera; both sera and urine will be stored at -80°C in the laboratory. The levels of SLPI in the serum and in the urine will be quantitated by an ELISA assay by using the "Human SLPI Quantikine ELISA Kit".

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SLPI and Clinical data	Correlation between clinical data of prostate cancer and SLPI levels	through study completion, at least 15 months
SLPI and Pathological data	Correlation between pathological data of prostate cancer and SLPI levels	Enrollment
SLPI and Molecular Features	Correlation between molecular features of prostate cancer and SLPI levels	Enrollment

Collaborators and Investigators

• Sponsor: University of Florence
• Collaborators: Azienda Ospedaliero-Universitaria Careggi; Istituto per lo Studio, la Prevenzione e la Rete Oncologica
• Investigators: Principal Investigator: Rosario Notaro, MD, ISPRO

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: April 13, 2021
• First Submitted That Met QC Criteria: April 17, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Prostate Cancer; Prostate; SLPI
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Serine Proteinase Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; HIV Protease Inhibitors; Secretory Leukocyte Peptidase Inhibitor
• Other Study ID Numbers: 17931

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No