The Role of the Heat-Shock Proteins in Esophagogastric Cancer

Tustumi, Francisco; Agareno, Gabriel Andrade; Galletti, Ricardo Purchio; Silva, Rafael Benjamim Rosa da; Quintas, Julia Grams; Sesconetto, Lucas de Abreu; Szor, Daniel José; Wolosker, Nelson

doi:10.3390/cells11172664

Cited by 8 publications

(5 citation statements)

References 86 publications

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“…Additionally, Hsp40 facilitates the binding of Hsp70 to the Hsp90-Hop (heat shock organizing protein) complex for further control of the protein folding [ 22 , 23 , 24 ]. Taking into consideration the protective role of HSPs, the overexpression of chaperones was reported in various types of solid and hematological malignancies [ 25 , 26 , 27 , 28 , 29 ]. High expression of HSPs also correlated to the chemo- and radioresistance of tumors indicated the possibility of employing these proteins as prognostic and/or diagnostic markers [ 26 , 30 , 31 , 32 , 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Babi¹,

Menlibayeva²,

Bex³

et al. 2022

Cancers

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Heat shock proteins (HSPs) are conservative and ubiquitous proteins that are expressed both in prokaryotic and eukaryotic organisms and play an important role in cellular homeostasis, including the regulation of proteostasis, apoptosis, autophagy, maintenance of signal pathways, protection from various stresses (e.g., hypoxia, ionizing radiation, etc.). Therefore, HSPs are highly expressed in tumor cells, including malignant brain tumors, where they also associate with cancer cell invasion, metastasis, and resistance to radiochemotherapy. In the current review, we aimed to assess the diagnostic and prognostic values of HSPs expression in CNS malignancies as well as the novel treatment approaches to modulate the chaperone levels through the application of inhibitors (as monotherapy or in combination with other treatment modalities). Indeed, for several proteins (i.e., HSP10, HSPB1, DNAJC10, HSPA7, HSP90), a direct correlation between the protein level expression and poor overall survival prognosis for patients was demonstrated that provides a possibility to employ them as prognostic markers in neuro-oncology. Although small molecular inhibitors for HSPs, particularly for HSP27, HSP70, and HSP90 families, were studied in various solid and hematological malignancies demonstrating therapeutic potential, still their potential was not yet fully explored in CNS tumors. Some newly synthesized agents (e.g., HSP40/DNAJ inhibitors) have not yet been evaluated in GBM. Nevertheless, reported preclinical studies provide evidence and rationale for the application of HSPs inhibitors for targeting brain tumors.

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Section: Introductionmentioning

confidence: 99%

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Babi¹,

Menlibayeva²,

Bex³

et al. 2022

Cancers

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“…Prognostication, a pivotal aspect of cancer care, can be significantly enhanced through the exploration of HSPs in EC. This investigation holds promise for refining prognostic predictions, tailoring treatment approaches, and ultimately improving patient outcomes[ 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, HSPs could assist in indicating specific palliative, adjuvant, or neoadjuvant chemotherapy or radiotherapy regimens. Profiling HSPs has the potential to improve precision in EC management, enabling the categorization of patients based on their likelihood of responding to chemotherapy[ 48 ]. This knowledge could spare some patients from unnecessary treatment and enhance OS.…”

Section: Discussionmentioning

confidence: 99%

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer: A systematic review and meta-analysis

Nakamura,

Park,

Pereira

et al. 2024

World J Gastrointest Oncol

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BACKGROUND Heat shock proteins (HSPs) are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overexpressed in many cancers. The prognostic significance of HSPs and their regulatory factors, such as heat shock factor 1 (HSF1) and CHIP, are poorly understood. AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer. METHODS A systematic review was conducted in accordance with PRISMA recommendations (PROSPERO: CRD42022370653), on Embase, PubMed, Cochrane, and LILACS. Cohort, case-control, and cross-sectional studies of patients with esophagus or esophagogastric cancer were included. HSP-positive patients were compared with HSP-negative, and the endpoints analyzed were lymph node metastasis, tumor depth, distant metastasis, and overall survival (OS). HSPs were stratified according to the HSP family, and the summary risk difference (RD) was calculated using a random-effect model. RESULTS The final selection comprised 27 studies, including esophageal squamous cell carcinoma (21), esophagogastric adenocarcinoma (5), and mixed neoplasms (1). The pooled sample size was 3465 patients. HSP40 and 60 were associated with a higher 3-year OS [HSP40: RD = 0.22; 95% confidence interval (CI): 0.09-0.35; HSP60: RD = 0.33; 95%CI: 0.17-0.50], while HSF1 was associated with a poor 3-year OS (RD = -0.22; 95%CI: -0.32 to -0.12). The other HSP families were not associated with long-term survival. HSF1 was associated with a higher probability of lymph node metastasis (RD = -0.16; 95%CI: -0.29 to -0.04). HSP40 was associated with a lower probability of lymph node dissemination (RD = 0.18; 95%CI: 0.03-0.33). The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis. CONCLUSION The expression levels of certain families of HSP, such as HSP40 and 60 and HSF1, are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

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“…Typically, these and other chaperones are cytoprotective, but if abnormal in structure–function, quantity, and/or location, they can cause diseases, known as chaperonopathies [ 9 , 10 ]. Chaperones can favor carcinogenesis through various mechanisms, as shown by many experimental and clinical data [ 11 , 12 , 13 ]. For example, high tissue levels of certain Hsps are often associated with cancer progression and invasiveness, suggesting that these proteins favor, in some types of tumors, the tendency to invade surrounding tissues and to spread to distant organs [ 6 , 7 , 14 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

Immunomorphological Patterns of Chaperone System Components in Rare Thyroid Tumors with Promise as Biomarkers for Differential Diagnosis and Providing Clues on Molecular Mechanisms of Carcinogenesis

Paladino

Santonocito

Graceffa

et al. 2023

Cancers

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Hurthle cell (HC), anaplastic (AC), and medullary (MC) carcinomas are low frequency thyroid tumors that pose several challenges for physicians and pathologists due to the scarcity of cases, information, and histopathological images, especially in the many areas around the world in which sophisticated molecular and genetic diagnostic facilities are unavailable. It is, therefore, cogent to provide tools for microscopists to achieve accurate diagnosis, such as histopathological images with reliable biomarkers, which can help them to reach a differential diagnosis. We are investigating whether components of the chaperone system (CS), such as the molecular chaperones, can be considered dependable biomarkers, whose levels and distribution inside and outside cells in the tumor tissue could present a distinctive histopathological pattern for each tumor type. Here, we report data on the chaperones Hsp27, Hsp60, and Hsp90. They presented quantitative levels and distribution patterns that were different for each tumor and differed from those of a benign thyroid pathology, goiter (BG). Therefore, the reported methodology can be beneficial when the microscopist must differentiate between HC, AC, MC, and BG.

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The Role of the Heat-Shock Proteins in Esophagogastric Cancer

Cited by 8 publications

References 86 publications

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer: A systematic review and meta-analysis

Immunomorphological Patterns of Chaperone System Components in Rare Thyroid Tumors with Promise as Biomarkers for Differential Diagnosis and Providing Clues on Molecular Mechanisms of Carcinogenesis

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