Craif and Tokyo Medical University Hospital report in the journal Cancers that high expression of miR-186-5p and miR-425-5p tracked with longer progression free survival, median 15.0 months versus 3.27 months. The study covered 12 patients, 7 responders and 5 non-responders.

Craif Inc., a bio-AI startup working on early cancer detection, said today that a joint study with Yosuke Hirasawa, Lecturer and head of the medical office in the Department of Urology at Tokyo Medical University Hospital, and colleagues has been published in the academic journal Cancers. The study asked whether microRNA measured in urine can predict which patients with urothelial carcinoma respond to an immune checkpoint inhibitor (ICI).

The study covered 12 patients: 7 who responded to ICI treatment and 5 who did not. Urine collected before treatment started separated the two groups by microRNA profile, and Craif says urinary microRNA could therefore become a promising biomarker for predicting response. Craif adds that the approach may reach beyond a single cancer type, to patient stratification and trial design in the clinical development of immune-related therapies generally.

What the study found

• Urinary microRNA profiles could classify urothelial carcinoma patients into ICI responders and non-responders.
• Differential expression analysis identified 10 microRNAs that differed significantly between the responder and non-responder groups.
• High expression of miR-186-5p and miR-425-5p in particular was associated with significantly longer progression free survival (PFS). The source describes this as suggesting clinical usefulness as markers for predicting efficacy.

The numbers

Differential expression analysis found 6 microRNAs significantly changed in expression in the responder group and 4 in the non-responder group.

For miR-186-5p and miR-425-5p, which were elevated in responders, patients in the high expression group had significantly longer PFS than the low expression group: median 15.0 months versus 3.27 months.

For miR-30a-5p and miR-542-3p, which were elevated in non-responders, the high expression group had shorter PFS than the low expression group: median about 3 months versus about 15 months.

The study also identified microRNAs that are sensitive to blood in the urine, miR-486-5p and miR-23a-3p among them, which the authors say shows why data quality control and sample preprocessing matter in future analyses.

Why a urine test would matter here

• Because testing needs only a urine sample, it may allow patients likely to benefit to be selected in advance, including cases where taking tissue is difficult.
• It may allow unnecessary dosing of patients who are unlikely to benefit to be avoided, which could lower the risk of side effects and the cost of care.
• Craif expects analysis of urinary microRNA to contribute to efficient use of limited medical resources, and to better patient stratification and higher success rates in trials of immune-related therapies.

Background

ICIs have improved treatment results in many cancers, urothelial carcinoma among them, but response rates are still limited and a meaningful number of patients get no benefit. When patients likely to benefit cannot be stratified in advance, the cost is unnecessary adverse event risk and higher healthcare spending, and at the development stage it is trial failure risk and longer timelines.

Predicting ICI response usually relies on pathology of tumor tissue, but depending on where the tumor sits and the condition of the patient, enough tissue cannot always be taken. The source calls establishing a noninvasive biomarker that can predict response with high accuracy before treatment starts an urgent issue.

The study looked at whether the profile of microRNA in urine, which can be collected with little burden on the patient, can predict the effect of ICI treatment.

How the study was done

Urine samples from 12 patients with urothelial carcinoma, 7 ICI responders and 5 non-responders, were collected before treatment began. Exosomes were extracted from the urine, RNA was purified, and small RNA sequencing was performed. The resulting data were analyzed statistically for association with treatment outcome. 

What Craif says this means

Predicting the effect of ICI treatment from urinary microRNA is noninvasive and simple, and because the test can be repeated it keeps the burden on the patient to a minimum. Craif says using the technique could improve the precision of patient selection and help optimize treatment strategy, and that in the development of new drugs it could contribute to more efficient clinical trials and higher success rates.

Definitions

• Immune checkpoint inhibitor (ICI): a drug that releases the mechanism cancer cells use to escape the immune system and raises the immune response.
• MicroRNA (miRNA): short RNA molecules that regulate gene expression, drawing attention as markers for cancer diagnosis and for predicting prognosis.
• Progression free survival (PFS): the period from the start of treatment until the disease progresses or the patient dies. One measure of treatment effect.

Publication information

• Journal: Cancers
• Title: Urinary microRNAs as prognostic biomarkers for predicting the effect of immune check point inhibitors in patients with urothelial carcinoma
• Authors: Yosuke Hirasawa, Atsushi Satomura, Mitsuo Okada, Mieko Utsugi, Hiroki Ogura, Tsuyoshi Yanagi, Yuta Nakamori, Masayuki Takehara, Kokichi Murakami, Go Nagao, Takeshi Kashima, Naoya Satake, Yoriko Ando, Motoki Mikami, Mika Mizunuma, Yuki Ichikawa, Yoshio Ohno
• DOI: 10.3390/cancers17162640

About Craif

Craif is a bio-AI startup founded in 2018 that works on early cancer detection. It combines AI with its own analytical platform, NANO IP (NANO Intelligence Platform), which detects a range of biomarkers including DNA and microRNA at high accuracy from urine and other body fluids, and develops tests intended to make very early detection of cancer, early treatment, and early return to normal life possible. Craif's stated vision is a society where people live out their natural lifespan.

Company details

• Company: Craif Inc.
• Representative: Ryuichi Onose, Representative Director
• Founded: May 2018
• Business: research and development of next generation tests for early detection of disease and personalized medicine, centered on cancer, and provision of the miSignal series of urine cancer risk tests
• Headquarters: THE PORTAL iidabashi B1F, 8-30 Shin-Ogawamachi, Shinjuku-ku, Tokyo

URL: https://craif.com/