Dataset Information

The Biological Context of C-Reactive Protein as a Prognostic Marker in Renal Cell Carcinoma: Studies on the Acute Phase Cytokine Profile.

ABSTRACT: High serum levels of the acute phase protein C-reactive protein (CRP) are associated with an adverse prognosis in renal cancer. The acute phase reaction is cytokine-driven and includes a wide range of inflammatory mediators. This overall profile of the response depends on the inducing event and can also differ between patients. We investigated an extended acute phase cytokine profile for 97 renal cancer patients. Initial studies showed that the serum CRP levels had an expected prognostic association together with tumor size, stage, nuclear grading, and Leibovich score. Interleukin (IL)6 family cytokines, IL1 subfamily mediators, and tumor necrosis factor (TNF)? can all be drivers of the acute phase response. Initial studies suggested that serum IL33R? (the soluble IL33 receptor ? chain) levels were also associated with prognosis, although the impact of IL33R? is dependent on the overall cytokine profile, including seven IL6 family members (IL6, IL6R?, gp130, IL27, IL31, CNTF, and OSM), two IL1 subfamily members (IL1RA and IL33R?), and TNF?. We identified a patient subset characterized by particularly high levels of IL6, IL33R?, and TNF? alongside an adverse prognosis. Thus, the acute phase cytokine reaction differs between renal cancer patients, and differences in the acute phase cytokine profile are associated with prognosis.

SUBMITTER: Aarstad HH

PROVIDER: S-EPMC7409073 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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The Biological Context of C-Reactive Protein as a Prognostic Marker in Renal Cell Carcinoma: Studies on the Acute Phase Cytokine Profile.

Aarstad Helene Hersvik HH Guðbrandsdottir Gigja G Hjelle Karin M KM Bostad Leif L Bruserud Øystein Ø Tvedt Tor Henrik Anderson THA Beisland Christian C

Cancers 20200719 7

High serum levels of the acute phase protein C-reactive protein (CRP) are associated with an adverse prognosis in renal cancer. The acute phase reaction is cytokine-driven and includes a wide range of inflammatory mediators. This overall profile of the response depends on the inducing event and can also differ between patients. We investigated an extended acute phase cytokine profile for 97 renal cancer patients. Initial studies showed that the serum CRP levels had an expected prognostic associa ...[more]

PMID: 32707675

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Project description:C-reactive protein (CRP) is one of the major members of the family of acute phase proteins (APP). Interest in this CRP was the result of a seminal discovery of its pattern of response to pneumococcal infection in humans. CRP has the unique property of reacting with phosphocholine-containing substances, such as pneumococcal C-polysaccharide, in the presence of Ca2+. The attention regarding the origin of CRP and its multifunctionality has gripped researchers for several decades. The reason can be traced to the integrated evolution of CRP in the animal kingdom. CRP has been unequivocally listed as a key indicator of infectious and inflammatory diseases including autoimmune diseases. The first occurrence of CRP in the evolutionary ladder appeared in arthropods followed by molluscs and much later in the chordates. The biological significance of CRP has been established in the animal kingdom starting from invertebrates. Interestingly, the site of synthesis of CRP is mainly the liver in vertebrates, while in invertebrates it is located in diverse tissues. CRP is a multifunctional player in the scenario of innate immunity. CRP acts as an opsonin in the area of complement activation and phagocytosis. Interestingly, CRP upregulates and downregulates both cytokine production and chemotaxis. Considering various studies of CRP in humans and non-human animals, it has been logically proposed that CRP plays a common role in animals. CRP also interacts with Fcγ receptors and triggers the inflammatory response of macrophages. CRP in other animals such as primates, fish, echinoderms, arthropods, and molluscs has also been studied in some detail which establishes the evolutionary significance of CRP. In mammals, the increase in CRP levels is an induced response to inflammation or trauma; interestingly, in arthropods and molluscs, CRP is constitutively expressed and represents a major component of their hemolymph. Investigations into the primary structure of CRP from various species revealed the overall relatedness between vertebrate and invertebrate CRP. Invertebrates lack an acquired immune response; they are therefore dependent on the multifunctional role of CRP leading to the evolutionary success of the invertebrate phyla.

Project description:BackgroundFactors contributing to the lack of understanding of research studies include poor reporting practices, such as selective reporting of statistically significant findings or insufficient methodological details. Systematic reviews have shown that prognostic factor studies continue to be poorly reported, even for important aspects, such as the effective sample size. The REMARK reporting guidelines support researchers in reporting key aspects of tumor marker prognostic studies. The REMARK profile was proposed to augment these guidelines to aid in structured reporting with an emphasis on including all aspects of analyses conducted.MethodsA systematic search of prognostic factor studies was conducted, and fifteen studies published in 2015 were selected, three from each of five oncology journals. A paper was eligible for selection if it included survival outcomes and multivariable models were used in the statistical analyses. For each study, we summarized the key information in a REMARK profile consisting of details about the patient population with available variables and follow-up data, and a list of all analyses conducted.ResultsStructured profiles allow an easy assessment if reporting of a study only has weaknesses or if it is poor because many relevant details are missing. Studies had incomplete reporting of exclusion of patients, missing information about the number of events, or lacked details about statistical analyses, e.g., subgroup analyses in small populations without any information about the number of events. Profiles exhibit severe weaknesses in the reporting of more than 50% of the studies. The quality of analyses was not assessed, but some profiles exhibit several deficits at a glance.ConclusionsA substantial part of prognostic factor studies is poorly reported and analyzed, with severe consequences for related systematic reviews and meta-analyses. We consider inadequate reporting of single studies as one of the most important reasons that the clinical relevance of most markers is still unclear after years of research and dozens of publications. We conclude that structured reporting is an important step to improve the quality of prognostic marker research and discuss its role in the context of selective reporting, meta-analysis, study registration, predefined statistical analysis plans, and improvement of marker research.

Dataset Information

The Biological Context of C-Reactive Protein as a Prognostic Marker in Renal Cell Carcinoma: Studies on the Acute Phase Cytokine Profile.

Publications

The Biological Context of C-Reactive Protein as a Prognostic Marker in Renal Cell Carcinoma: Studies on the Acute Phase Cytokine Profile.

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