Early detection of colorectal adenocarcinoma: a clinical decision support tool based on plasma porphyrin accumulation and risk factors

Lualdi, Manuela; Cavalleri, A; Battaglia, Luigi; Colombo, Ambrogio; Garrone, G; Morelli, Daniele; Pignoli, E.; Sottotetti, Elisa; Leo, Ermanno

doi:10.1186/s12885-018-4754-2

Cited by 13 publications

(15 citation statements)

References 36 publications

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“…Increased plasma levels of porphyrins, especially zinc protoporphyrin and coproporphyrin, are found in patients with diseases other than porphyrias, such as in colorectal adenocarcinoma. 141 Secondary elevations of porphyrins are often misinterpreted, but can be differentiated by analyzing porphyrin precursors and porphyrins in urine, stool, plasma, and heparinized blood, as performed by specialized porphyria laboratories or centers (Table 1). 142,143…”

Section: Secondary Elevation In Porphyrinsmentioning

confidence: 99%

Clinical Guide and Update on Porphyrias

Stölzel¹,

Doss²,

Schuppan³

2019

Gastroenterology

109

132

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Physicians should be aware of porphyrias, which could be responsible for unexplained gastrointestinal, neurologic, or skin disorders. Despite their relative rarity and complexity, most porphyrias can be easily defined and diagnosed. They are caused by well-characterized enzyme defects in the complex heme biosynthetic pathway and are divided into categories of acute vs non-acute or hepatic vs erythropoietic porphyrias. Acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and aminolevulinic acid dehydratase deficient porphyria) manifest in attacks and are characterized by overproduction of porphyrin precursors, producing often serious abdominal, psychiatric, neurologic, or cardiovascular symptoms. Patients with variegate porphyria and hereditary coproporphyria can present with skin photosensitivity. Diagnosis relies on measurement of increased urinary 5-aminolevulinic acid (in patients with aminolevulinic acid dehydratase deficient porphyria) or increased 5-aminolevulinic acid and porphobilinogen (in patients with other acute porphyrias). Management of attacks requires intensive care, strict avoidance of porphyrinogenic drugs and other precipitating factors, caloric support, and often heme therapy. The non-acute porphyrias are porphyria cutanea tarda, erythropoietic protoporphyria, X-linked protoporphyria, and the rare congenital erythropoietic porphyria. They lead to the accumulation of porphyrins that cause skin photosensitivity and occasionally severe liver damage. Secondary elevated urinary or blood porphyrins can occur in patients without porphyria, for example, in liver diseases, or iron deficiency. Increases in porphyrin precursors and porphyrins are also found in patients with lead intoxication. Patients with porphyria cutanea tarda benefit from iron depletion, hydroxychloroquine therapy, and, if applicable, elimination of the hepatitis C virus. An a-melanocytestimulating hormone analogue can reduce sunlight sensitivity in patients with erythropoietic protoporphyria or Xlinked protoporphyria. Strategies to address dysregulated or dysfunctional steps within the heme biosynthetic pathway are in development.

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Section: Secondary Elevation In Porphyrinsmentioning

confidence: 99%

Clinical Guide and Update on Porphyrias

Stölzel¹,

Doss²,

Schuppan³

2019

Gastroenterology

109

132

View full text Add to dashboard Cite

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“…ALA-FGR thus maximizes the extent of tumor resection with improved prognosis for patients. In this context, the question arose whether or not PPIX blood levels could be used to monitor tumor regrowth, because the spectral characteristics of blood from cancer patients differ from those of control subjects [8][9][10][11].…”

Section: Figurementioning

confidence: 99%

“…Both high mass accuracy and the possibility of breaking the analyte molecules in the gas phase and measuring their fragments (MS/MS) contribute to unequivocal species identification, because complex samples can often not be fully chromatographically resolved. HPLC-MS was applied for the determination of porphyrin profiles in biological matrices [11,[39][40][41][42][43] using predominantly electrospray ionization (ESI) interfaces. Additionally, there were efforts to explore atmospheric pressure chemical ionization [42] for the purpose.…”

Section: Mass Spectrometrymentioning

confidence: 99%

“…For the investigation of porphyrins in blood, predominantly plasma or red blood cells were used [11,40,43]. In plasma, MS was applied for the quantification of coproporphyrin isomers for monitoring of drug interactions [43], the elucidation of fluorescing compounds after detection of elevated fluorescence [11], and the qualitative analysis of porphyrin patterns facilitating the differential diagnosis of human porphyrias [40]. Despite all these efforts, no short and sensitive HPLC-MS/MS method for specific PPIX quantification from whole blood or serum was yet available although great data have been shown for less complex cell culture extracts [44,45].…”

Section: Structures Of Type I and Iii Isomers Of Uro-and Coproporphyrmentioning

confidence: 99%

“…More recently, besides the analysis of porphyrin metabolites [39] and profiles for toxicological and pharmacological applications [40][41][42], PPIX has been investigated as tumor marker for bladder, colorectal and kidney cancer [10,11,32]. Tumor cells are able to produce porphyrins naturally or after administration of ALA, which is also reflected in elevated plasma fluorescence of cancer patients.…”

Section: Protoporphyrin Ix: a Potential Biomarker For Cancer Screeningmentioning

confidence: 99%

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Protoporphyrin IX Analysis from Blood and Serum in the Context of Neurosurgery of Glioblastoma

Walke¹,

Molina²,

Stummer³

et al. 2021

Mass Spectrometry in Life Sciences and Clinical Laboratory

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Protoporphyrin IX (PPIX) is formed from δ-aminolevulinic acid (ALA) during heme biosynthesis. Due to its cyclic tetrapyrrole core structure, it absorbs in the visible region of the electromagnetic spectrum and is thus colored. Both ALA and PPIX have become of great interest to neurosurgery, because in high-grade glioma, ALA diffuses into the tumor and is converted to PPIX. Fluorescence-guided resection (FGR) takes advantage of both the enrichment of PPIX in the tumor and its fluorescent properties, which enable visualization of tumor tissue. ALA-mediated FGR thus maximizes the extent of resection with better prognosis for patients. Tumor cells are able to produce porphyrins naturally or after administration of ALA, which is also reflected in elevated plasma fluorescence of cancer patients. PPIX might thus serve as a biomarker for monitoring of the tumor burden. A liquid chromatography-mass spectrometry (LC-MS)-based method is presented to quantify PPIX in blood and serum in the context of current fluorescence-based diagnostics. The method is able to distinguish between zinc PPIX, a component of red blood cells of importance in the detection of lead poisoning and iron deficiency anemia, and metal-free PPIX. In a proof-of-principle study, it was used to follow a time course of a glioblastoma patient undergoing surgery and confirmed elevated PPIX blood levels before ALA administration. During surgery, these blood levels increased about four-fold. The here developed 10 min reversed-phase LC-target MS method now allows patient screening with high specificity and throughput.

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Protoporphyrin IX purification from blood and serum for mass analysis – Considerations with respect to neurosurgery

Walke

König

2021

Rapid Comm Mass Spectrometry

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Protoporphyrin (PPIX) and its precursor 5-aminolevulinic acid (ALA) are routinely used in fluorescence-guided resection (FGR) in neurosurgery of glioblastoma. Orally administered prior to surgery, ALA diffuses preferentially into the tumour-bearing brain region and is there transformed into PPIX as part of the heme biosynthesis.During the resection of high-grade gliomas (HGG), the fluorescent properties of PPIX enable the differentiation of healthy and malignant brain tissueresulting in a more complete tumour resection and, ultimately, a better prognosis for patients. 1,2 Despite the use of ALA-FGR, complete tumour removal is impossibledue to the infiltrative growth of HGG, e.g., glioblastoma multiforme (GBM), tumours often reoccur. Clinical diagnosis of HGG/GBM is furthermore not straightforward and requires expensive imaging technology as well as tissue biopsies. So far, the prognosis for GBM patients remains one of the lowest in modern day oncology. 1,3,4 We thus investigated PPIX as a potential blood biomarker for the diagnosis of primary and recurrent GBM using liquid chromatography/mass spectrometry (LC/MS). 5 Some cancer research studies to that effect using plasma have already been published. [6][7][8] It was also demonstrated that extracellular vesicles originating from glioma cells contained PPIX, 9 but none of these investigations used mass spectrometry (MS) as detector.Whole blood contains the most PPIX, but it is not the best matrix for such studies, because of unspecific contributions from erythrocyte ZnPPIX. For serum or plasma, though, the published PPIX levels,

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Early detection of colorectal adenocarcinoma: a clinical decision support tool based on plasma porphyrin accumulation and risk factors

Cited by 13 publications

References 36 publications

Clinical Guide and Update on Porphyrias

Clinical Guide and Update on Porphyrias

Protoporphyrin IX Analysis from Blood and Serum in the Context of Neurosurgery of Glioblastoma

Protoporphyrin IX purification from blood and serum for mass analysis – Considerations with respect to neurosurgery

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