Autophagy-related Prognostic Signature in HER2 Positive Gastric
Carcinomas

Ieni, Antonio; Pizzimenti, Cristina; Giuffrè, Giuseppe; Caruso, Rosario Alberto; Tuccari, Giovanni

doi:10.2174/1566524021666211123093532

Cited by 3 publications

(2 citation statements)

References 47 publications

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“…Negative controls were obtained by omitting the specific antisera and substituting PBS for the primary antibody. The assessment of p62 immunoreactivity was evaluated according to the intensity and percentage of positively stained cells, as elsewhere reported ( 2 , 4 ). The cytoplasmic and nuclear immunostaining intensity was rated as follows: 0, negative; 1, weak; and 2, strong.…”

Section: Methodsmentioning

confidence: 99%

“…Autophagy, already defined as an intracellular catabolic phenomenon, is considered to be involved in many pathophysiological processes, such as infection, autoimmune disease, neurodegenerative disorders, aging, cell death, and cancer (1)(2)(3)(4). In the neoplastic field, it is well established that autophagy may exert a dual role, suppressing or contributing to tumorigenesis (5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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Immunoexpression of p62/SQSTM1/Sequestosome‑1 in human primary and recurrent IDH1/2 wild‑type glioblastoma: A pilot study

et al. 2022

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Asbstract. p62/SQSTM1/Sequestosome-1 is an autophagic protein that serves a crucial role in cellular metabolism, proliferation and malignant growth. Notably, autophagy may influence the development and resistance to therapy of numerous types of human cancer. In the present pilot study, the immunohistochemical pattern of p62 was analyzed in a cohort of patients with isocitrate dehydrogenase (IDH)1/2 wild-type glioblastoma (GBM), in primary and recurrent samples, in order to verify the concordance or discordance between the primary and recurrent tumors. In addition, the association between p62, and patient outcome and O 6 -methylguanine-DNA methyltransferase (MGMT) status was assessed. The results revealed p62 immunoexpression in the nucleus and cytoplasm of neoplastic elements in 45% of primary and 55% of recurrent cases of GBM. A discordant p62 immunoreactivity was detected in 35% of cases, with a variation either with positive or negative conversion of p62 status. Statistically, p62 expression and MGMT status exhibited a significant prognostic value by univariate analysis, whereas only MGMT promoter methylation status emerged as an independent prognostic factor by multivariate analysis. Finally, the most favorable prognosis was documented when the same GBM case was positively concordant for both p62 expression and MGMT methylated status. Since little data are available regarding the association between p62 expression and MGMT in GBM, further investigations may be required to determine if new targeted therapies may be addressed against autophagy-related proteins, such as p62.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunoexpression of p62/SQSTM1/Sequestosome‑1 in human primary and recurrent IDH1/2 wild‑type glioblastoma: A pilot study

et al. 2022

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Immunohistochemical Profile of p62/SQSTM1/Sequestosome‐1 in Human Low‐ and High‐Grade Intracranial Meningiomas

Ieni,

Pizzimenti,

Fiorentino

et al. 2024

Analytical Cellular Pathology

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Among autophagic‐related proteins, p62/SQSTM1/Sequestosome‐1 represents a relevant actor in cellular proliferation and neoplastic growth. Although, recently, p62 expression has been analyzed in different neurodegenerative and glial neoplastic diseases, no available information have been reported in meningiomas, which have an high epidemiological relevance being the second most common category of intracranial tumors after gliomas. Generally meningiomas have a benign behavior, but their recurrence is not uncommon mainly when atypical or anaplastic varieties occur. However, intranuclear vacuoles have been ultrastructurally observed in meningiomas, and they were labelled by p62 antibodies. Therefore, in the present study, we have investigated p62 immunohistochemical pattern in a cohort of 133 cases representative of low‐ and high‐grade meningiomas, to verify if p62 expression may be related to clinicopathological data, thus achieving a potential prognostic role. The p62 immunoexpression was frequently found in the nucleus and cytoplasm of neoplastic elements, and utilizing an intensity‐distribution score, 55 (41.3%) cases were considered as high expressors while 78 (58.7%) cases were instead recorded as low expressors. Fifteen cases exhibited recurrences of the disease, 14 of which were codified as high expressors. Moreover, a direct relationship between p62 and Mib‐1 immunoexpression as well as between p62 and neoplastic grade have been documented. Finally, we suggest that impaired autophagic flux with an increase in p62 expression may be involved in the activation of NRF2 also contributing in the development of recurrence in meningioma patients.

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Role of ATG4 Autophagy-Related Protein Family in the Lower Airways of Patients with Stable COPD

Nucera,

Di Stefano,

Ricciardolo

et al. 2024

IJMS

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Autophagy is a complex physiological pathway mediating homeostasis and survival of cells degrading damaged organelles and regulating their recycling. Physiologic autophagy can maintain normal lung function, decrease lung cellular senescence, and inhibit myofibroblast differentiation. It is well known that autophagy is activated in several chronic inflammatory diseases; however, its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and the expression of autophagy-related genes (ATGs) in lower airways of COPD patients is still controversial. The expression and localization of all ATG proteins that represented key components of the autophagic machinery modulating elongation, closure, and maturation of autophagosome membranes were retrospectively measured in peripheral lungs of patients with stable COPD (n = 10), control smokers with normal lung function (n = 10), and control nonsmoking subjects (n = 8) using immunohistochemical analysis. These results show an increased expression of ATG4 protein in alveolar septa and bronchiolar epithelium of stable COPD patients compared to smokers with normal lung function and non-smoker subjects. In particular, the genes in the ATG4 protein family (including ATG4A, ATG4B, ATG4C, and ATG4D) that have a key role in the modulation of the physiological autophagic machinery are the most important ATGs increased in the compartment of lower airways of stable COPD patients, suggesting that the alteration shown in COPD patients can be also correlated to impaired modulation of autophagic machinery modulating elongation, closure, and maturation of autophagosomes membranes. Statistical analysis was performed by the Kruskal–Wallis test and the Mann–Whitney U test for comparison between groups. A statistically significant increased expression of ATG4A (p = 0.0047), ATG4D (p = 0.018), and ATG5 (p = 0.019) was documented in the bronchiolar epithelium as well in alveolar lining for ATG4A (p = 0.0036), ATG4B (p = 0.0054), ATG4C (p = 0.0064), ATG4D (p = 0.0084), ATG5 (p = 0.0088), and ATG7 (p = 0.018) in patients with stable COPD compared to control groups. The ATG4 isoforms may be considered as additional potential targets for the development of new drugs in COPD.

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Autophagy-related Prognostic Signature in HER2 Positive Gastric Carcinomas

Cited by 3 publications

References 47 publications

Immunoexpression of p62/SQSTM1/Sequestosome‑1 in human primary and recurrent IDH1/2 wild‑type glioblastoma: A pilot study

Immunoexpression of p62/SQSTM1/Sequestosome‑1 in human primary and recurrent IDH1/2 wild‑type glioblastoma: A pilot study

Immunohistochemical Profile of p62/SQSTM1/Sequestosome‐1 in Human Low‐ and High‐Grade Intracranial Meningiomas

Role of ATG4 Autophagy-Related Protein Family in the Lower Airways of Patients with Stable COPD

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