Acute-phase response proteins are related to cachexia and accelerated angiogenesis in gastroesophageal cancers

Krzystek−Korpacka, Małgorzata; Matusiewicz, Małgorzata; Diakowska, Dorota; Grabowski, Krzysztof; Blachut, Katarzyna; Kustrzeba−Wójcicka, Irena; Terlecki, Grzegorz; Gamian, Andrzej

doi:10.1515/cclm.2008.089

Cited by 78 publications

(54 citation statements)

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“…[23] These observations are in agreement with previous findings demonstrating that CRP levels correlate with cachexia in cancer patients. [56,57] An increase in CRP levels is associated with a decrease in albumin levels, and this is also a feature characteristic of the cachectic syndrome. [9,10] Recent research indicates that vitamin D has antiinflammatory properties, which might contribute to its beneficial effects in multiple cancers.…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

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Background and Objective: In patients with advanced cancer, cachexia correlates with low performance status and poor quality of life. In addition, cachexia may be associated with reduced response to chemoradiotherapy and a poor prognosis in cancer patients. Nearly all forms of cachexia are closely associated with chronic inflammation and elevated levels of inflammatory and pro-inflammatory circulating factors, including C-reactive protein (CRP), which is considered a valid laboratory and clinical marker. Among the different pathways involved in the production of inflammatory cytokines and chemokines, the vitamin Dvitamin D receptor (VDR) axis plays a fundamental role.In this study, we explore the possible association between CRP and key factors pertaining to the vitamin D axis -in particular, VDR gene polymorphisms -in cancer patients with cachexia. Although certain tumor types are more commonly associated with cachexia, even within the same tumor type there are significant differences in the extent and duration of cachexia. Such variations may be due to polymorphisms of the VDR gene that could lead to cachexia-prone genotypes or to cachexia-resistant genotypes. Identification of such genotypes could be very helpful in the management of cancer patients. Methods: Forty-three cancer patients were recruited by the Nutritional Unit of the Prato Hospital. Data on age, gender, type of cancer, stage of cancer, and nutritional assessment, as well as transferrin, ferritin, albumin, and CRP levels, were collected. Genomic DNA was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction. BsmI, ApaI, TaqI, and FokI polymorphisms of the VDR gene were investigated using the respective restriction enzymes. For the different VDR polymorphisms, the absence or presence of the restriction sites were designated with capital or small letters, respectively. For example, for the BsmI polymorphism, the presence of the undigested fragment identified the B allele, whereas the presence of the digested fragment identified the b allele. Results: Cancer patients with cachexia have higher CRP levels compared with non-cachectic cancer patients, independently from the genotype. In cachectic patients, the presence of specific VDR BsmI and TaqI alleles was associated with higher CRP levels. In particular, the VDR b and T alleles were more frequent in cachectic cancer patients with elevated CRP levels than in cachectic patients with normal CRP levels. Conclusion: From these results, we hypothesize that there is an association between BsmI and TaqI VDR gene polymorphisms and the cachectic syndrome. In particular, we propose that in cancer patients, the concomitance of b and T alleles with elevated CRP levels may represent an early clinical predictor for the development of a more aggressive form of cachexia.

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Section: Discussionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

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“…This association could be explained by a variety of tumour-related phenomena, including enhanced tumour progression (Hefler et al, 2008), angiogenesis (Krzystek-Korpacka et al, 2008), and metastasis (Weinstein et al, 1984). However, the presence of systemic inflammation has also been linked with both hypermetabolism (Falconer et al, 1994) and reduced food intake , two key components of the cachexia syndrome that is known to result in shortened survival in patients with advanced malignancy .…”

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confidence: 99%

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

et al. 2010

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BACKGROUND: Macrophage inhibitory cytokine-1(MIC-1) is a potential modulator of systemic inflammation and nutritional depletion, both of which are adverse prognostic factors in oesophago-gastric cancer (OGC). METHODS: Plasma MIC-1, systemic inflammation (defined as plasma C-reactive protein (CRP) of X10 mg l -1 or modified Glasgow prognostic score (mGPS) of X1), and nutritional status were assessed in newly diagnosed OGC patients (n ¼ 293). Healthy volunteers (n ¼ 35) served as controls. RESULTS: MIC-1 was elevated in patients (median ¼ 1371 pg ml -1 ; range 141 -39 053) when compared with controls (median ¼ 377 pg ml -1 ; range 141 -3786; Po0.001). Patients with gastric tumours (median ¼ 1592 pg ml -1 ; range 141 -12 643) showed higher MIC-1 concentrations than patients with junctional (median ¼ 1337 pg ml -1 ; range 383 -39 053) and oesophageal tumours (median ¼ 1180 pg ml -1 ; range 258 -31 184; P ¼ 0.015). Patients showed a median weight loss of 6.4% (range 0.0 -33.4%), and 42% of patients had an mGPS of X1 or plasma CRP of X10 mg l -1 (median ¼ 9 mg l -1 ; range 1 -200). MIC-1 correlated positively with disease stage (r 2 ¼ 0.217; Po0.001), age (r 2 ¼ 0.332; Po0.001), CRP (r 2 ¼ 0.314; Po0.001), and mGPS (r 2 ¼ 0.336; Po0.001), and negatively with Karnofsky Performance Score (r 2 ¼ À0.269; Po0.001). However, although MIC-1 correlated weakly with dietary intake (r 2 ¼ 0.157; P ¼ 0.031), it did not correlate with weight loss, BMI, or anthropometry. Patients with MIC-1 levels in the upper quartile showed reduced survival (median ¼ 204 days; 95% CI 157 -251) when compared with patients with MIC-1 levels in the lower three quartiles (median ¼ 316 days; 95% CI 259 -373; P ¼ 0.036), but MIC-1 was not an independent prognostic indicator. CONCLUSIONS: There is no independent link between plasma MIC-1 levels and depleted nutritional status or survival in OGC.

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“…[10] Esophageal cancer is particularly important among cancers associated with cachexia. [5] Cachexia is responsible for 30%-50% of cancer-related deaths among digestive tract malignancies. [11] Not only have 80% of patients newly diagnosed with gastrointestinal tract malignancies experienced substantial weight loss, but some molecularly alterated characteristics of cachexia have also been observed, even in the absence of weight loss.…”

Section: Discussionmentioning

confidence: 99%

“…In several studies, increased serum C-reactive protein (CRP) levels have been shown to be associated with poor prognosis in patients with esophageal cancer. [2][3][4][5] Prealbumin and transferrin are negative acute phase reactants whose serum levels decrease in patients with malignancy and malnutrition. [6] The aim of this study was to investigate the prognostic value of serum CRP, prealbumin, and transferrin levels in patients with advanced stage esophageal cancer treated with stent placement.…”

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confidence: 99%

Prognostic importance of serum CRP, prealbumin, and transferrin levels in patients with advanced stage esophageal cancer

Aydın¹

2011

Turkish J Thorac Cardiovasc Surg

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Amaç: Bu çalışmada stent takılarak tedavi edilen ileri evre özofagus kanserli hastalarda serum C-reaktif protein (CRP), prealbumin ve transferrin düzeylerinin prognostik değeri araştırıldı. Ça lış ma pla nı: Temmuz 2007 ve Aralık 2008 tarihleri arasında gerçekleştirilen prospektif randomize bir çalış-mada lokal olarak ilerlemiş hastalık veya uzak organ metastazı nedeniyle stent takılarak tedavi edilen ardışık 61 hastada, stent takılmadan 1-3 gün önce serum CRP, prealbumin ve transferrin düzeyleri çalışıldı. Tüm hastalar ölünceye kadar takip edildi. Bul gu lar: Stent tüm hastalarda başarı ile takılarak oral alım tekrar sağlandı. İşleme bağlı mortalite gözlenmedi. Hastaların ortalama sağkalım süresi 164.3±120.3 gün (dağılım 15-450 gün) idi. Serum CRP seviyesi ≥10 mg/L olan hastalarda (n=38) ortalama sağkalım 103.2±82.3 gün iken serum CRP seviyesi <10 mg/L olan hastalarda (n=23) ortalama sağkalım 265.4±121.2 gün idi. Serum prealbumin seviyesi ≥15 mg/L olan hastalarda (n=28) ortalama sağkalım 237.5±132.7 gün iken serum prealbumin seviyesi <15 mg/L olan hastalarda (n=33) ortalama sağkalım 102.3±79.6 gün idi. Serum transferrin seviyesi ≥200 mg/L olan hastalarda (n=25) ortalama sağkalım 211.6±130.2 gün iken serum transferrin seviyesi <200 mg/L olan hastalarda (n=36) ortalama sağkalım 131.5±113.8 gün idi. Referans serum CRP, prealbumin ve transferrin seviyelerinin sağ-kalımla ilişkisi istatistiksel olarak anlamlı idi (sırasıyla p<0.001, p<0.001 ve p= 0.003). So nuç: İleri evre özofagus kanserli hastalarda özofageal stent uygulamasından önce serum CRP, prealbumin ve transferrin düzeyleri kolaylıkla saptanabilir ve hastaların prognozları hakkında fikir elde edilebilir.Anah tar söz cük ler: C-reaktif protein; özofagus kanseri; prealbü-min; sağkalım; transferrin.Background: This study investigated the prognostic value of serum C-reactive protein (CRP), prealbumin, and transferrin levels in patients with advanced stage esophageal cancers treated with stent placement. Methods: In a prospective, randomized study conducted between July 2007 and December 2008, serum CRP, prealbumin, and transferrin levels were determined 1-3 days prior to stent placement in 61 consecutive patients who underwent stent placement due to locally advanced disease or distant organ metastasis. All patients were followed until death. Results:The stent was successfully placed in all patients and oral intake was restored. There was no procedure-related mortality. The mean survival period of the patients was 164.3±120.3 days (range 15 to 450 days). Whereas the mean survival period was 103.2±82.3 days in patients with a serum CRP level ≥10 mg/L (n=38), it was 265.4±121.2 days in patients with a serum CRP level <10 mg/L (n=23). While the mean survival period was 237.5±132.7 days in patients with a serum prealbumin level ≥15 mg/L (n=28), the mean survival period was 102.3±79.6 days in patients with a serum prealbumin level <15 mg/L (n=33). The mean survival period was 211.6±130.2 days in patients with a serum transferrin level ≥200 mg/L (n=25) while the mean ...

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Acute-phase response proteins are related to cachexia and accelerated angiogenesis in gastroesophageal cancers

Abstract: Cachexia in gastroesophageal cancers is associated with changes in APRP concentrations. This, together with a direct relationship of APRPs with accelerated angiogenesis, may constitute a foundation for the association of APRPs and GPS with outcome in these malignancies.

Cited by 78 publications

References 30 publications

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

Prognostic importance of serum CRP, prealbumin, and transferrin levels in patients with advanced stage esophageal cancer

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