Inflammation. [3] SedRate, Fibrinogen... - Advanced Prostate...

Advanced Prostate Cancer

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Inflammation. [3] SedRate, Fibrinogen, IL-6, TNFalpha.

7 years ago•2 Replies

There are a number of markers of inflammation & the perfect test to assess one's inflammation status might involve markers not previously mentioned in:

"Inflammation. [1] Neutrophil-to-Lymphocyte Ratio [NLR]" &

"Inflammation. [2] Albumin & C-Reactive Protein [CRP]"

However, the NLR & Albumin are usually included in a basic blood panel, & CRP has become a common test. I don't know how much added value the following have, but they are mentioned in PCa studies. The exception is the Sedimentation Rate (Sed Rate), which my GP likes as a general-purpose single test [3].

[1] Sedimentation Rate (Sed Rate).

The Sed Rate is not a specific inflammation marker in the sense that CRP is.

[1a] "The erythrocyte sedimentation rate (ESR) is the rate at which red blood cells sediment in a period of one hour. It is a common hematology test, and is a non-specific measure of inflammation."

"The ESR is governed by the balance between pro-sedimentation factors, mainly fibrinogen, and those factors resisting sedimentation, namely the negative charge of the erythrocytes (zeta potential). When an inflammatory process is present, the high proportion of fibrinogen in the blood causes red blood cells to stick to each other. The red cells form stacks called 'rouleaux,' which settle faster, due to their increased density."

[2] Fibrinogen.

Fibrinogen is a two-edged problem. Circulating levels represent clotting potential, & levels rise with inflammation. While fibrin clots can be life-threatening, the immediate concern in PCa is the role of micro-clots as a facilitator of metastasis. A circulating PCa cell that docks with a micro-clot can avoid being zapped. At the same time, elevated fibrinogen is a sign of inflammation, which is itself associated with progression

This post is concerned with fibrinogen only as an inflammation marker.

[2a] (2016 - Sweden)

"This study was aimed to determine the association between PSA levels and biomarkers of subclinical systemic inflammation based on data from 119 middle-aged healthy men from the general population."

"Serum levels of PSA and biomarkers of systemic inflammation (CRP and fibrinogen) were measured. ... Subjects were divided into two groups according to PSA levels; < 2 ng/ml and ≥ 2 ng/ml."

"Men with PSA values ≥ 2 ng/ml had significantly higher levels of fibrinogen as compared to those with PSA < 2 ng/ml ... In a multivariate regression analysis model adjusted for the age of subjects, BMI, marital status, smoking, snuff, and alcohol intake with serum levels of PSA as a dependent variable, serum level of fibrinogen predicted higher PSA-values (odds ratio = 3.30 ...)"

[2b] (2014 - U.S.)

"Serum prostate specific antigen (PSA) may be elevated in otherwise healthy men; systemic inflammation has been associated with cancer. The study of systemic inflammatory markers in men without clinical prostate disease, but with elevated PSA may characterize the subgroup of men at higher risk for subsequent prostate cancer."

"Elevated serum PSA (194 men, 6.1% of the total), was significantly associated with plasma fibrinogen (ORmultiv = 1.88 ...), and NLR (ORmultiv = 1.14 ...), after adjustment for age, smoking, body mass index, education, race, co-morbidities, and use of medications."

[2c] (2016 - U.K. / Sweden / Germany / Greece)

"D-dimers and fibrinogen were increased in prostate cancer"

This is interesting, since, not only was fibrinogen increased (a marker of inflammation), but the increase led to fibrin clots (D-dimer is only produced from fibrin).

[2d] (2016 - U.S.)

"Advanced disease (regardless of subtype) is associated with significantly higher expression of prothrombin {&} fibrinogen ..."

(Prothrombin leads to thrombin, which acts on fibrinogen to produce fibrin clots.)

[2e] (2016 - China)

"Pretreatment plasma fibrinogen as an independent prognostic indicator of prostate cancer patients treated with androgen deprivation therapy."

"The pretreatment plasma fibrinogen level was associated with tumor progression and might have a significant role in the prognosis of the prostate cancer patients treated with ADT."

[2f] (2015 - Austria)

"... revealed a significant correlation between increased plasma fibrinogen and {Cancer-specific survival}. Univariable analysis also showed a significant association between the elevated plasma fibrinogen level and decreased {overall survival} (HR 3.242 ...), that remained significant in multivariable analysis (HR 3.215 ...)"

[2g] (2012 - Slovakia)

"This is the first study that demonstrates the significant increase in {serum fibrinogen} in PCa patients on ADT, while CRP as inflammatory marker did not increase."

[3] Interleukin-6 [IL-6]

IL-6 is an acute phase protein - a cytokine.

[3a] "Cancer Patients Typically Have Increased Interleukin-6 Levels".

[3b] (2005 - Greece)

"The role of proinflammatory cytokines in biochemical pathways of neoplastic growth has been established in prostate cancer, along with evidence for high levels of interleukin (IL)-6 among patients with hormone refractory disease."

[3c] (2011 - U.S.)

"As an established mediator of inflammation, interleukin-6 (IL-6) is implicated to facilitate prostate cancer progression to androgen independence through transactivation of the androgen receptor. However, whether IL-6 has a causative role in de novo prostate tumorigenesis was never investigated. We now provide the first evidence that IL-6 can induce tumorigenic conversion and further progression to an invasive phenotype of non-tumorigenic benign prostate epithelial cells. Moreover, we find that paracrine IL-6 stimulates the autocrine IL-6 loop and autocrine activation of insulin-like type I growth factor receptor (IGF-IR) to confer the tumorigenic property ..."

[3d] (2011 - U.S.)

"Metastatic events to the bone occur frequently in numerous cancer types such as breast, prostate, lung, and renal carcinomas, melanoma, neuroblastoma, and multiple myeloma. Accumulating evidence suggests that the inflammatory cytokine interleukin (IL)-6 is frequently upregulated and is implicated in the ability of cancer cells to metastasize to bone. IL-6 is able to activate various cell signaling cascades that include the STAT (signal transducer and activator of transcription) pathway, the PI3K (phosphatidylinositol-3 kinase) pathway, and the MAPK (mitogen-activated protein kinase) pathway. Activation of these pathways may explain the ability of IL-6 to mediate various aspects of normal and pathogenic bone remodeling, inflammation, cell survival, proliferation, and pro-tumorigenic effects. This review article will discuss the role of IL-6: 1) in bone metabolism, 2) in cancer metastasis to bone, 3) in cancer prognosis, and 4) as potential therapies for metastatic bone cancer."

[3e] (2014 - Switzerland)

"Environmental and genetic aspects are reflected in the development of prostate cancer. In this context, there is growing evidence that chronic inflammation is involved in the regulation of cellular events in prostate carcinogenesis, including disruption of the immune response and regulation of the tumour microenvironment. One of the best surrogates of chronic inflammation in prostate cancer is interleukin 6 (IL-6). Serum IL-6 levels are elevated in patients with untreated metastatic or castration-resistant prostate cancer (CRPC) and correlate negatively with tumour survival and response to chemotherapy. Via multiple signal pathways including the Janus tyrosine family kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, the extracellular signal-regulated kinase 1 and 2 (ERK1/2)-mitogen activated protein kinase (MAPK) pathway, and the phosphoinositide 3-kinase (PI3-K) pathway, IL-6 is able to promote prostate cancer cell proliferation and inhibit apoptosis in vitro and in vivo. IL-6 is associated with aggressive prostate cancer phenotype and may be involved in the metastatic process through regulation of epithelial-mesenchymal transition (EMT) and homing of cancer cells to the bone. A substantial body of evidence suggests that IL-6 plays a major role in the transition from hormone-dependent to CRPC, most notably through accessory activation of the androgen receptor."

[4] Tumor necrosis factor alpha [TNFalpha, TNFα]

[4a] TNFalpha "is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction."

[4b] (1998 - Japan)

"The present study was undertaken to evaluate the relationship between serum tumor necrosis factor (TNF) and cachexia in patients with prostate cancer. TNF levels were determined in 110 serum samples from prostate cancer patients by an enzyme immunoassay. Serum TNF activity was positive in 76% of the patients with relapsed disease, whereas only 11% of the untreated patients and 0% of the patients in remission as a result of endocrine therapy were positive."

"Patients with elevated serum TNF levels had a significantly higher mortality rate ... than those with undetectable serum TNF levels. These findings suggest that TNF may be one of the factors contributing to the complex syndrome of cachexia in patients with prostate cancer."

[4c] (2013 - Russia)

While TNFalpha is associated with aggressive disease, increased expression of a TNF receptor (soluble receptor for TNF) is also bad news.

"... 85 patients with morphologically verified diagnosis of prostate cancer ..."

"During follow-up the relative risk of poor prognosis increased by 3 times, and death-in 8.7 times with increasing concentrations of soluble receptors for TNF."

[5] Conclusion.

Some might view the above as TMI, but there will be reference to each of the inflammation markers when I post:

"Inflammation. [4] How to Change the Numbers"

-Patrick

[1a] en.wikipedia.org/wiki/Eryth...

[2a] ncbi.nlm.nih.gov/pmc/articl...

[2b] ncbi.nlm.nih.gov/pubmed/244...

[2c] ncbi.nlm.nih.gov/pubmed/280...

[2d] ncbi.nlm.nih.gov/pubmed/271...

[2e] ncbi.nlm.nih.gov/pubmed/269...

[2f] ncbi.nlm.nih.gov/pubmed/254...

[2g] ncbi.nlm.nih.gov/pubmed/228...