ABSTRACT
Obesity is a risk factor for pancreatic cancer development, partly due to the tissue environment of metabolic disorder-related inflammation. We aimed to detect a tissue environment marker triggered by obesity-related metabolic disorders related to pancreatic cancer progression. In murine experiments, Bl6/j mice fed a normal diet (ND) or a high-fat diet (HFD) were orthotopically injected with mPKC1, a murine-derived pancreatic cancer cell line. We used stocked sera from 140 pancreatic cancer patients for analysis and 14 colon polyp patients as a disease control. Compared with ND-fed mice, HFD-fed mice exhibited obesity, larger tumors, and worse prognoses. RNA sequencing of tumors identified tenascin C (TNC) as a candidate obesity-related serum tissue environment marker with elevated expression in tumors of HFD-fed mice. Serum TNC levels were greater in HFD-fed mice than in ND-fed mice. In pancreatic cancer patients, serum TNC levels were greater than those in controls. The TNC-high group had more metabolic disorders and greater CA19-9 levels than did the TNC-low group. There was no relationship between serum TNC levels and disease stage. Among 77 metastatic patients treated with chemotherapy, a high serum TNC concentration was an independent poor prognostic factor. Pancreatic cancer patients with high serum TNC levels experienced progression more rapidly.
Subject(s)
Biomarkers, Tumor , Diet, High-Fat , Inflammation , Pancreatic Neoplasms , Tenascin , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/pathology , Tenascin/blood , Animals , Humans , Prognosis , Mice , Male , Inflammation/blood , Diet, High-Fat/adverse effects , Female , Middle Aged , Biomarkers, Tumor/blood , Obesity/blood , Obesity/complications , Aged , Cell Line, Tumor , Metabolic Diseases/blood , Mice, Inbred C57BLABSTRACT
Resumo O aneurisma da aorta abdominal corresponde a uma dilatação anormal, enquanto a dissecção aórtica aguda é uma delaminação da túnica média com formação de um falso lúmen. A Tenascina-C é uma glicoproteína que pode ser encontrada em situações de lesão tecidual. Nesse sentido, este artigo pretendeu avaliar se a Tenascina-C pode auxiliar na avaliação do prognóstico do aneurisma da aorta abdominal e da dissecção aórtica aguda. Realizou-se uma revisão integrativa da literatura em que foram considerados elegíveis quatro artigos, sendo que dois associaram maiores níveis da Tenascina-C a fatores de proteção e menor risco de lesões, enquanto dois correlacionaram com prognóstico pior. Alguns autores acreditam que a Tenascina-C poderia ser um biomarcador elegível, mas esses estudos ainda são inconclusivos no que diz respeito a seu papel no desfecho clínico dos pacientes com aneurismas.
Abstract Abdominal aortic aneurysm is an abnormal dilatation, while acute aortic dissection is a delamination of the tunica media, forming a false lumen. Tenascin-C is a glycoprotein that can be found in situations involving tissue damage. The objective of this article is to evaluate whether Tenascin-C assays could be of use for predicting prognosis in abdominal aortic aneurysms and acute aortic dissection. We conducted an integrative literature review, for which four articles were considered eligible. Two of these studies associated higher Tenascin-C levels with protective factors and lower risk of injury, whereas the other two correlated them with worse prognosis. Some authors believe that Tenascin-C could be a candidate biomarker, but these studies are still inconclusive with regard to its role in the clinical outcomes of patients with aneurysms.