In precision oncology, tissue quality plays a pivotal role in maintaining data integrity. We explore the impact of standardizing tissue collection and processing on data quality, and how this helps enhance patient outcomes as well as our understanding of cancer.
Insights from tissue samples play an important role across the drug life cycle – from early discovery, through to clinical use post launch.
During early drug discovery and development, tissue samples are used to study processes involving biomolecules such as DNA, RNA and proteins. This helps advance our understanding of cancer pathways, helping scientists identify biomarkers and potential targets for therapy.
In the clinical setting, clinicians use tissues to study tissue morphology to diagnose cancers and stage them, as well as to determine treatment plans for patients.
The importance of tissue quality in precision oncology research
Senior Director Oncology Analytics Indivumed Therapeutics
“Due to their continued importance across clinical research and practice, it is pivotal to get tissue quality right,” stated Dr. Daniel Pohlmann, Senior Director Oncology Analytics at the German founded global oncology company Indivumed Therapeutics.
“Tissues can transition away from their original disease state with notable biological changes occurring in as little as fifteen minutes once the samples are taken from the patient. This limits the amount of time the sample can remain chilled before being processed, known as the cold ischemic time. If processing is not done promptly, it can alter relevant biomolecules including proteins or RNA in the tissue, compromising the integrity of the generated datasets.”
Low-quality data which has lost biologically relevant signals can result in analytical artifacts. This can lead to false negative outcomes causing a drug target to be overlooked, which may result in a potentially effective treatment not being developed. In clinical practice, a biomarker not being identified in time may cause a patient to lose the chance of receiving a therapy that performs better.
“On the other hand, poor tissue quality can introduce false positives,” added Pohlmann. “This means a signal that results from changes induced by degradation processes is picked up, and a treatment is developed based on this false signal.”
Thus, low-quality tissue samples can have significant repercussions for research in pharmaceutical or biotech companies, highlighted Pohlmann. They can lead to misinterpretation of data, potentially causing delays in drug development or failure of drug candidates in later development phases.
By standardizing tissue quality, both false positives and negatives can be minimized. This helps ensure the reliability of findings in biomarker-based discovery, patient stratification and treatment identification.
Thus, starting with high quality tissue is crucial in protecting investments in resources and time, and most importantly patient lives.
Critical considerations in the sample collection process
Patient tissue collection happens at hospital-associated biobanks, often at the point of surgery, noted Pohlmann: “In most cases, tissue collection needs to be seamlessly integrated into a medical procedure, as it is only one of the elements of the surgery where a patient is getting treated for their condition.”
“To ensure suitability of the sample for downstream research processes, various factors need to be taken into account, like cold ischemia time or the amount of tumor and adjacent normal tissue that needs to be extracted,” he continued. “Integrating such factors into medical procedures requires sophisticated protocols and communication with the hospital staff.”
Elaborating on why these considerations are critical, Pohlmann said that scientists today utilize a multi-omics approach to gain a comprehensive understanding into a patient’s condition. This involves analysis and integration of multiple layers of biological data, including genomics, transcriptomics, proteomics, and more.
Integrating biological insights in this manner from a single source eliminates variability caused by genetic differences, enabling researchers to identify accurate treatment targets.
“To be able to generate multiple layers of information, not only is the quality crucial, but a sufficient quantity of tissue needs to be collected from the patient,” he explained. “Moreover, comparing data from cancerous tissue versus non-cancerous tissue from the same patient can provide contextual insights, making collection of adjacent normal tissue an advantage.”
In addition to tissue samples, another important factor is the collection of clinical data – spanning basic patient information, treatment history, and patient outcomes – which provides vital information on patient stratification.
“Cancer is a heterogeneous disease where patients may respond differently to the same treatment,” Pohlmann said. “Thus, collecting sufficient samples along with detailed clinical information ultimately provides a holistic overview of individual variations, enabling patient sub-grouping.”
Adapting tissue processing based on analysis requirements
Once the fresh tissue samples are collected at the clinics, they are transported on dry ice to laboratories where they undergo processing so as to retain integrity for subsequent analysis. Various processing approaches can be applied to the collected solid tissue depending on the specific objectives of the downstream analyses.
“Formalin-fixed, paraffin-embedded (FFPE) tissues are traditionally used for diagnostic purposes in the clinical setting,” shared Pohlmann. “They provide valuable insights into tissue morphology and disease pathology, helping in accurately diagnosing cancer.”
FFPE samples are preserved using formaldehyde, making them easier to store, process as well as handle compared to other approaches. However, they do not effectively preserve proteins and other sensitive biomolecules, which are essential for identifying potential biomarkers and cancer pathways.
In contrast, fresh frozen tissues, processed by snap freezing the samples using liquid nitrogen, are better suited for pre-clinical research. While this method does not retain morphological details, it preserves cellular proteins and RNA effectively, enabling multi-omics analysis to be conducted, offering an insight into natural physiology.
However, the complex organization involved in obtaining, storing and processing fresh frozen tissues can be labor- and time- intensive, which makes this method more complex than FFPE processing.
Lastly, tissues can also be frozen in a cryo-protective medium that prevents cellular damage. This makes it possible to recover viable cells from these cryopreserved tissues, which allows future development of patient-derived tumor models.
These models closely mimic the patient’s physiological processes and are crucial in understanding tumor heterogeneity, validating novel targets and biomarkers, and hence advancing drug development.
“Ultimately, irrespective of the processing approach, tissue samples must remain in a consistent cold chain from collection to analysis to reduce the risk of sample degradation and preserve sample integrity,” asserted Pohlmann.
A holistic precision oncology workflow with a commitment to quality
Regardless of the site, personnel or approach used to collect and process the tissues, standardization helps ensure consistency by minimizing the introduction of bias, mentioned Pohlmann. Indivumed’s unwavering commitment to standardized procedures since the company’s inception two decades ago has been key in gaining its position today at the forefront of precision oncology research, he noted.
“We have standard operating procedures (SOPs) covering our holistic precision oncology workflow from tissue collection, to quality control, processing and data analysis,” explained Pohlmann. “These protocols are not only followed in-house but are also upheld by our external partners, ensuring consistency in sample handling.”
As part of its standard procedures, Indivumed obtains its high-quality tumor and adjacent tissue samples from its extensive clinical partner network of hospitals worldwide. The data from these samples powers Indivumed’s truly global cancer database, representing different local treatment regimens and care.
To ensure that vital morphological or physiological information is not lost from patient tissue after extraction, Indivumed’s SOPs prescribe strict sample processing time-limits (within 10 minutes of extraction).
In parallel, the Indivumed team obtains clinical information spanning around 320 individual data points from each patient. This is supplemented over time with longitudinal data to build a full picture on the patients’ condition. Thus, Indivumed’s samples include clinical data on disease progression and treatment outcomes over time, providing valuable insights into patient trajectories and helping identify high-risk groups.
“Moreover, irrespective of the type of processing, our tissues need to pass rigorous pathological quality checks to be deemed eligible for inclusion into our analytical databases,” elaborated Pohlmann. “This includes assessment of tumor content, necrosis, inflammation, and tissue-specific characteristics such as fibrosis in liver tissue.”
To identify any potential technical variations during collection, processing or data analysis, the Indivumed team also documents every step in the tissue sample’s journey. This comprehensive tracking system permits accurate data interpretation and potential future normalization of data if required.
Looking to the future, Pohlmann emphasized that effective oncology research will continue to be built on the foundation of high-quality tissue material. Until recently, cancer research was heavily focused on precision in the analytics space. The attention was on designing high-throughput and high-resolution instruments.
“But of late, the value of high quality biomaterials is starting to get acknowledged as equally important to data integrity,” he said. “Indivumed was one of the few privileged companies that recognized this importance early on, which allowed us to structure our procedures to prioritize tissue quality from the very start. This has had a huge impact in optimizing the early discovery workflow we offer today, where our standardized sample collection makes downstream steps in developing precision therapies – including data generation and subsequent analysis – more precise.”
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Images courtesy: Indivumed