Protein expression profiling of plasma and lungs at different stages of metastatic development in a human triple negative breast cancer xenograft model

Tveitarås, Maria K.; Selheim, Frode; Sortland, Kristina; Reed, Rolf K.; Stuhr, Linda Elin Birkhaug

doi:10.1371/journal.pone.0215909

Cited by 16 publications

(10 citation statements)

References 39 publications

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“…Moreover, elevated CRP levels are considered as an independent and significant prognostic indicator in patients with NSCLC [8,9,10]. Other acute phase proteins, including haptoglobin, alpha-2 macroglobulin and alpha1-antitrypsin (AAT) are also suggested as suitable targets for therapeutic and biomarker discoveries in cancer [11,12].…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of SERPINA1 Gene and Its Encoded Alpha1-antitrypsin Protein in NSCLC

Ercetin

Richtmann

Delgado

et al. 2019

Cancers

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High expression of SERPINA1 gene encoding acute phase protein, alpha1-antitrypsin (AAT), is associated with various tumors. We sought to examine the significance of SERPINA1 and AAT protein in non-small-cell lung cancer (NSCLC) patients and NSCLC cell lines. Tumor and adjacent non-tumor lung tissues and serum samples from 351 NSCLC patients were analyzed for SERPINA1 expression and AAT protein levels. We also studied the impact of SERPINA1 expression and AAT protein on H1975 and H661 cell behavior, in vitro. Lower SERPINA1 expression in tumor but higher in adjacent non-tumor lung tissues (n = 351, p = 0.016) as well as higher serum levels of AAT protein (n = 170, p = 0.033) were associated with worse survival rates. Specifically, in NSCLC stage III patients, higher blood AAT levels (>2.66 mg/mL) correlated with a poor survival (p = 0.002). Intriguingly, levels of serum AAT do not correlate with levels of C-reactive protein, neutrophils-to-leukocyte ratio, and do not correlate with SERPINA1 expression or AAT staining in the tumor tissue. Additional experiments in vitro revealed that external AAT and/or overexpressed SERPINA1 gene significantly improve cancer cell migration, colony formation and resistance to apoptosis. SERPINA1 gene and AAT protein play an active role in the pathogenesis of lung cancer and not just reflect inflammatory reaction related to cancer development.

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Section: Introductionmentioning

confidence: 99%

Clinical Significance of SERPINA1 Gene and Its Encoded Alpha1-antitrypsin Protein in NSCLC

Ercetin

Richtmann

Delgado

et al. 2019

Cancers

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“…Especially in the context of clinical proteomics, cancerous tissue proteomic analysis provides the most accurate reflection of the tumor's physiological state (19)(20)(21)(22). However, most protein MS-based breast cancer screening strategies refer to female patients and although possible biomarkers have been identified, few have been validated so as to achieve clinical application (23)(24)(25)(26). Regarding protein-CANCER GENOMICS & PROTEOMICS 19: 229-240 (2022) 234 Figure 3.…”

Section: Discussionmentioning

confidence: 99%

High-throughput Proteomic Profiling of Male Breast Cancer Tissue

Zografos

Proikakis

Anagnostopoulos

et al. 2022

Cancer Genomics Proteomics

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Background/Aim: Until now, little emphasis has been placed on the protein expression profile of male breast cancer (MBC) tumors, due to the rarity of the disease. The present study aimed to identify a proteomic pattern that is characteristic for malignant male breast tissue epithelium. Materials and Methods: The protein content of four male breast tumors and corresponding adjacent healthy (control) tissues was analyzed by high-throughput nano-liquid chromatography-MS/MS technology. Results: A total of 2,352 proteins were identified, that correspond to 1,249 single gene products, with diverse biological roles. Of those, a panel of 119 differentially expressed tissue proteins was identified in MBC samples compared to controls; 90 were found to be over-expressed in MBC tissues, while 29 were downregulated. Concurrently, 844 proteins were detected only in MBC tumors and 197 were expressed exclusively in control mammary samples. Conclusion: Differential proteomic expression was found in MBC tissue, leading to improved understanding of MBC pathology and highlighting the need for personalized management of male patients. Male breast cancer (MBC) is an uncommon disease, accounting for fewer than 1% of all diagnosed breast carcinoma cases (1). The estimates of the American Cancer Society, that predict merely 2,650 new cases of invasive MBC and 530 deaths from the disease in the United States for 2021, indicate its limited impact on male morbidity and mortality (2). Despite the fact that this entity is rare, the incidence of MBC is on the rise over the past two decades (3), attracting increasing interest in terms of deciphering its biology, etiopathogenesis, clinical presentation and unique management. Still, because of the low number of diagnoses, MBC remains understudied, prospective research-based progress is hindered, and decision-making for patients and physicians is based on observational retrospective studies (4, 5).Owning to the scarcity of research in the field, clinical data on the management of MBC are usually extrapolated from trials on its female counterpart; this approach is becoming less and less acceptable due to the inherent discrepancies between the two entities. Characteristically, the largest retrospective collection and pathological review of MBC tumor samples so far, showed a lack of association between histological grading and outcome, which may be linked to the different distribution of disease subtypes in men compared with women (6). For example, men are much more likely to express the estrogen (ER) or androgen (AR) receptors than women, and less likely to over-express HER2 (6, 7). Lobular tumors are also much less frequent in men despite being relatively common in women, whereas most MBC cases are subtyped as either Luminal A-like or Luminal-B-like/HER-2-negative (6, 8). The genomic landscape of the disease further highlights the differences between sexes, with a recent publication reporting less frequent 16q losses, PIK3CA mutations, and TP53 mutations than those seen in ER-positive/HER2-negative...

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“…However, the authors emphasized the need to investigate its role as a TNBC biomarker more precisely. Recently, in a human triple-negative breast cancer xenograft model, dramatic up-regulation of plasma haptoglobin was observed after metastasis, suggesting the potential of HP as a biomarker for metastasis [ 116 ]. They also noticed a significant decrease in serum HP before the development of metastases.…”

Section: Circulating Proteins Produced By Tumour Tissuementioning

confidence: 99%

Circulating proteins as predictive and prognostic biomarkers in breast cancer

et al. 2022

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Breast cancer (BC) is the most common cancer and among the leading causes of cancer death in women. It is a heterogeneous group of tumours with numerous morphological and molecular subtypes, making predictions of disease evolution and patient outcomes difficult. Therefore, biomarkers are needed to help clinicians choose the best treatment for each patient. For the last years, studies have increasingly focused on biomarkers obtainable by liquid biopsy. Circulating proteins (from serum or plasma) can be used for inexpensive and minimally invasive determination of disease risk, early diagnosis, treatment adjusting, prognostication and disease progression monitoring. We provide here a review of the main published studies on serum proteins in breast cancer and elaborate on the potential of circulating proteins to be predictive and/or prognostic biomarkers in breast cancer.

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Protein expression profiling of plasma and lungs at different stages of metastatic development in a human triple negative breast cancer xenograft model

Cited by 16 publications

References 39 publications

Clinical Significance of SERPINA1 Gene and Its Encoded Alpha1-antitrypsin Protein in NSCLC

Clinical Significance of SERPINA1 Gene and Its Encoded Alpha1-antitrypsin Protein in NSCLC

High-throughput Proteomic Profiling of Male Breast Cancer Tissue

Circulating proteins as predictive and prognostic biomarkers in breast cancer

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