Detection of High Expression Levels of EMT-Transcription Factor mRNAs in Patients With Pancreatic Cancer and Their Diagnostic Potential

• Conditions: Pancreatic Cancer
• Interventions: Diagnostic Test: Liquid biopsy

• Registration Number: NCT04323917
• Lead Sponsor: Istituto Clinico Humanitas

Brief Summary

The present study is aimed at detecting and measuring mRNA levels of genes involved in epithelial to mesenchymal transition (EMT) in biological samples, i.e. in peripheral blood samples of pancreatic cancer (PC) patients and healthy controls, to determine the presence of disease, its progression and risk of recurrence.

Detailed Description

The investigators first provided evidence that human pancreatic cancer (PC) cells can undergo EMT during local invasion, and that EMT transcription factors (i.e.Twist family basic helix-loop-helix transcription factor 1 (TWIST1)) are increased in the blood of PC patients. In addressing the relevance of EMT in the metastatic process, the prognostic role of M-like cancer cells entering into the circulation remains to be determined.

Currently, the notion that cancer disseminates via the circulation led to increased attention on the identification of circulating tumor cells (CTCs) in blood samples ("liquid biopsy"; LB), so far exclusively based upon epithelial (E) markers. However, an un-biased evaluation of CTCs, providing meaningful information for cancer diagnosis up to therapy, cannot exclude cells with M features. LB data show that circulating TWIST1, zinc finger E-box binding homeobox 2 (ZEB2) and E-Cadherin (CDH1) messenger ribonucleic acids (mRNA) are significantly and steadily increased in the blood of PC patients.These findings indicate that high levels of EMT players in the circulation efficiently discriminate PC patients, irrespectively of tumor resectability.

The present study is aimed at detecting and measuring mRNA levels of genes involved in epithelial to mesenchymal transition in biological samples, i.e. in peripheral blood samples of tumor patients, to determine the presence of disease, its progression and risk of recurrence.

Aim of the study is to depict the molecular profile of EMT-Transcription factor (EMT-TFs) variations in the blood of patients with early, intermediate or advanced PC, with respect to disease progression and delivered treatments.

Primary endpoint: to determ the stage, the remission or the progression of a pancreatic cancer in a pancreatic cancer affected subjects. This end-point comprising the step of assaying a biological sample from said subject for the presence of a panel of mRNAs encoding for transcription factors involved in epithelial to mesenchymal transition.

Secondary endpoint: to identify biomarkers suitable for the selection of patients amenable of responsiveness to medical and surgical treatment.

Study Timeline

• Study Start: 2017-11-02
• Study First Submitted: 2019-12-20
• Study First Submitted QC: 2020-03-24
• Study First Posted: 2020-03-27
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-07
• Last Update Posted: 2020-08-10
• Primary Completion: 2021-11
• Study Completion: 2022-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 850

Inclusion Criteria

1. Males or females over 18 years of age capable of providing informed consent.
2. Pancreatic carcinoma confirmed by tissue biopsy or colon mass, clinically consistent with cancer and eventually confirmed by pathology.
3. Subject were enrolled following colon cancer screening via colonoscopy

Exclusion Criteria

1. Patients under the age of 18 years or over the age of 80 years.
2. Patients with personal history of cancer, identification of large polyp or adenomatous pathology on previous or subsequent colonoscopy
3. Patient with history of abdominal surgery within the past four months
4. Patients unwilling to or unable to give informed consent.
5. Patients with acute inflammatory diseases or under any emergency condition.
6. Pregnant women.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Controls	Liquid biopsy	Healthy Subject enrolled following colon cancer screening via colonoscopy
Cases	Liquid biopsy	Subjects affected by Pancreatic carcinoma (PC) confirmed by tissue biopsy

Primary Outcome Measures

Name	Time	Method
Assessments of diagnosis of PC by EMT-TF mRNA levels in blood	Analysis at day 0: at diagnosis or before surgery for PC patients; before colonoscopy in controls	To determine the stage, the remission or the progression of a pancreatic cancer in a pancreatic cancer affected subject not administered with an appropriate antitumor treatment (e.g., neo-adjuvant therapy) comprising the step of assaying a biological sample from said subject for the presence of a panel of mRNAs encoding for transcription factors involved in epithelial to mesenchymal transition.

Secondary Outcome Measures

Name	Time	Method
Prediction of prognosis of PC by EMT-TF mRNA levels in blood	Analysis at least: 7-15 days from surgery (T1), 30 days (T2) from surgery, 6 months (T3) from surgery, 1 year (T4) from surgery	To identify biomarkers suitable for the selection of PC patients amenable of responsiveness to medical and surgical treatment.

Trial Locations

Locations (1)

Istituto Clinico humanitas; 🇮🇹 Milan, Italy