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Use of HTG Transcriptome Panel (HTP) in Muscle Invasive Bladder Cancer (MIBC) Research

What is Muscle Invasive Bladder Cancer (MIBC)?

Urology Care Foundation describes that “ muscle invasive bladder cancer (MIBC) is a cancer that spreads into the detrusor muscle of the bladder. The detrusor muscle is the thick muscle deep in the bladder wall. This cancer is more likely to spread to other parts of the body.

In the U.S., bladder cancer is the third most common cancer in men. Each year, there are more than 83,000 new cases diagnosed in men and women. About 25% of bladder cancers are MIBC. Bladder cancer is more common as a person grows older. ”

Choices for Treatment

Treatments for muscle invasive bladder cancer include:

Cystectomy - Bladder removal followed by chemotherapy or without chemotherapy

Bladder Preservation - chemotherapy with radiation

Post Treatment Side Effects

  • Gastrointestinal (GI) problems
  • Urinary diversion
  • Hormonal changes
  • Reproductive health issues
  • Sexual dysfunction
  • Pain

Research

In a recent study titled “CK5/6 and GATA3 Defined Phenotypes of Muscle-Invasive Bladder Cancer: Impact in Adjuvant Chemotherapy and Molecular Subtyping of Negative Cases” multidisciplinary cohort of researchers from Frankfurt, Germany led by Dr. Henning Reis, looked at phenotypes of MIBC patients who expressed and did not express CK5/6 and GATA3, and evaluated the impacts of adjuvant chemotherapy and molecular subtyping on their survival rates.

As the publication explains, “ Identifying patients that benefit from cisplatin-based adjuvant chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC). The purpose of this study is to correlate “luminal” and “basal” type protein expression with histological subtypes, to investigate the prognostic impact on survival after adjuvant chemotherapy and to define molecular consensus subtypes of “double negative” patients (i.e., without expression of CK5/6 or GATA3).”

The researchers analyzed samples form 181 patients with MIBC: 86 samples were biopsied via transurethral resection of the bladder (TURB) procedure and 95 samples were from patients who underwent cystectomy.

Figure 1. Representative images of IHC staining of CK5/6 positive, GATA 3 positive, double negative, and double positive cases (magnification 200 ×).

The mRNA gene expression profiles (GEP) for the samples were obtained using a groundbreaking and novel transcriptome panel with 19.398 mRNA targets. The HTG Transcriptome Panel (HTP) is an ultra-efficient GEP tool which is expertly designed to provide extensive coverage of most human mRNA transcripts including isoforms. The panel can simultaneously interrogate 19,398 targets using Formalin Fixed Paraffin Embedded (FFPE), PAXgene and extracted RNA samples, generating data for up to 96 samples in less than three days. HTP utilizes a proprietary workflow and leverages the sensitivity and dynamic range of next-generation sequencing (NGS), allowing researchers to generate reliable results using limited sample amount. The technology is considered ultra-efficient because it allows small or archival samples to be processed in an extraction free protocol, saving precious samples, time, and resources.

Illustration : HTG EdgeSeq Workflow

 

By looking at comprehensive gene expression profiles the researchers found that the characteristics of double negative patients for whom there is currently no consensus for adjuvant treatment guidelines. Proper identification of patients’ subtypes can lead to personalized treatment regiment and therefore improve the chances of survival.

Figure 2. Kaplan–Meier curve for overall survival (OS) for patients with and without adjuvant chemotherapy.

Resources:

The full article and the supplemental materials can be accessed by clicking here.

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Page last updated June 24, 2022