Clinical trial NCT04323917: Detection of High Expression Levels of EMT-Transcription Factor mRNAs in Patients With Pancreatic Cancer and Their Diagnostic Potential
Official title: Detection of High Expression Levels of EMT-Transcription Factor mRNAs in Patients With Pancreatic Cancer and Their Diagnostic Potential
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pancreatic Cancer
Keywords: Epithelial to Mesenchymal Transition
EMT
PC
mRNA
EMT-TF
Diagnosis
Biomarkers
Liquid biopsy
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
Collaborators: name: IRCCS San Raffaele
First posted: 2020-03-27
Enrollment: 850
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a prospective pathological and molecular study of screening for pancreatic cancer. The main objectives of the trial are:

1. To develop a specific and reproducible assay for the detection pancreatic cancer based on blood RNA and to amplify cancer specific molecular markers using qPCR.
2. To correlate the presence of molecular markers in the samples with the presence of pancreatic cancer or pre-cancerous lesions.
3. To add additional biomarkers to the study panel of biomarkers. presence of colon cancer or pre-cancerous lesions. To add additional biomarkers to the study panel of biomarkers.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessments of diagnosis of PC by EMT-TF mRNA levels in blood
timeFrame: Analysis at day 0: at diagnosis or before surgery for PC patients; before colonoscopy in controls
Secondary outcomes:
measure: Prediction of prognosis of PC by EMT-TF mRNA levels in blood
timeFrame: Analysis at least: 7-15 days from surgery (T1), 30 days (T2) from surgery, 6 months (T3) from surgery, 1 year (T4) from surgery
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Istituto Clinico humanitas
Study officials:
References:
citation: Celesti G, Di Caro G, Bianchi P, Grizzi F, Basso G, Marchesi F, Doni A, Marra G, Roncalli M, Mantovani A, Malesci A, Laghi L. Presence of Twist1-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors. Gastroenterology. 2013 Sep;145(3):647-57.e15. doi: 10.1053/j.gastro.2013.05.011. Epub 2013 May 15.