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BMC Gastroenterology Nov 2021Heat shock protein 70 (HSP70) has been associated with the clinicopathological characteristics and prognosis of many cancers types, implying that it is a potential... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heat shock protein 70 (HSP70) has been associated with the clinicopathological characteristics and prognosis of many cancers types, implying that it is a potential cancer biomarker. However, no consensus has been reached regarding its clinicopathological and prognostic significance in patients with gastric cancer. To address this gap, we performed a systematic review and meta-analysis.
METHODS
We searched PubMed, Embase, and the Cochrane Library for full-text literature according to the eligibility criteria. We used the odds ratio and hazard ratio as the suitable parameters to evaluate the clinicopathological and prognostic significance of HSP70. The statistical analysis was performed using STATA 15.0.
RESULTS
After inclusion and exclusion of studies based on the eligibility criteria, data of 1,307 patients with gastric cancer from 9 studies were finally included. The pooled outcomes implied that HSP70 expression was significantly correlated with higher differentiation degrees, intestinal gastric cancer, and lymphovascular invasion but not with age, gender, depth of invasion, Helicobacter pylori infection, lymph node invasion, TNM stages, and metastasis. The pooled HR showed no significant correlation between HSP70 expression and overall survival of gastric cancer patients.
CONCLUSIONS
Our meta-analysis showed that HSP70 plays a complicated role in the development of gastric cancer. It may be directly engaged in tumour differentiation and distant invasion but cannot be considered a biomarker for predicting the prognosis of gastric cancer.
Topics: Biomarkers, Tumor; HSP70 Heat-Shock Proteins; Helicobacter Infections; Helicobacter pylori; Humans; Prognosis; Stomach Neoplasms
PubMed: 34809574
DOI: 10.1186/s12876-021-01990-4 -
Current Oncology (Toronto, Ont.) Nov 2022The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in... (Meta-Analysis)
Meta-Analysis
The endoplasmic reticulum chaperone BiP (also known as GRP-78 or HSPA5) maintains protein folding to allow cell proliferation and survival and has been implicated in carcinogenesis, tumor progression, and therapy resistance. BiP's association with clinical factors and prognostic potential in breast cancer remains unclear. In this work, three types of analysis were conducted to improve the knowledge of BiP's clinicopathological potential: (1) analysis of publicly available RNA-seq and proteomics datasets stratified as high and low quartiles; (2) a systematic review and meta-analysis of immunohistochemical detection of BIP; (3) confirmation of findings by BiP immunohistochemical detection in two luminal-like breast cancer small cohorts of paired samples (pre- vs. post-endocrine therapy, and primary pre- vs. metastasis post-endocrine therapy). The TCGA PanCancer dataset and CPTAC showed groups with high BiP mRNA and protein associated with HER2, basal-like subtypes, and higher immune scores. The meta-analysis of BiP immunohistochemistry disclosed an association between higher BiP positivity and reduced relapse-free survival. BiP immunohistochemistry confirmed increased BiP expression in metastasis, an association of BiP positivity with HER2 expression, and nuclear BiP localization with higher a tumor stage and poor outcome. Therefore, three independent approaches showed that BiP protein is associated with worse outcomes and holds prognostic potential for breast cancer.
Topics: Humans; Female; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Breast Neoplasms; Neoplasm Recurrence, Local; Prognosis
PubMed: 36547124
DOI: 10.3390/curroncol29120710 -
World Journal of Gastrointestinal... Apr 2024Heat shock proteins (HSPs) are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overexpressed...
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.
PubMed: 38660660
DOI: 10.4251/wjgo.v16.i4.1578 -
Medicine Jan 2021Heat-shock proteins (HSP) is a key chaperone protein which maintains intracellular proteostasis and is expressed on the surface of solid and hematological malignancies.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heat-shock proteins (HSP) is a key chaperone protein which maintains intracellular proteostasis and is expressed on the surface of solid and hematological malignancies. Several studies have reported paradoxical evidence of the association between HSP expression and prognosis of oral cancer. To address the discrepancy, we carried out the meta-analysis to assess the role of HSP such as: HSP70, HSP90, HSP27, HSP60, and HSP105 in susceptibility, progression, and prognosis of oral cancer.
MATERIALS AND METHODS
We retrieved the PubMed, Embase, Web of science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to acquire the eligible studies which were associated with HSP70, HSP90, HSP27, HSP60, and HSP105 protein expression and oral cancer. We applied hazard ratio (HR) and its 95% confidence interval (95% CI) to assess the value of HSP protein expression in overall survival of oral cancer; odds ratio (OR) and its 95% CI were used to evaluate the association of risk and clinical features of oral cancer. Funnel plot, Begg test, and Egger line regression test were utilized to observe publication bias among studies. All statistical analysis was performed with Stata 14.0 software (Stata Corporation, College Station, TX).
RESULTS
A total of 26 studies were included in the present meta-analysis. On based of the results, HSP70 and HSP27 had no significant association with progression of oral cancer. However, the pooled HR and 95% CI revealed a significant well effects of HSP70 and HSP27 expression on survival of oral cancer. Moreover, the susceptibility of oral cancer was significantly associated with HSP70 and HSP60 overexpression.
CONCLUSION
HSP70 and HSP27 protein overexpression might be valuable biomarkers for the prognosis of oral cancer. And HSP70 and HSP60 might have potential predictive effects on the risk of oral cancer.
Topics: HSP70 Heat-Shock Proteins; Heat-Shock Proteins; Humans; Mouth Neoplasms; Prognosis; Proportional Hazards Models
PubMed: 33546049
DOI: 10.1097/MD.0000000000024274 -
Journal of the Formosan Medical... Jan 2022A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia...
BACKGROUND/PURPOSE
A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence, then spreads to other limbs. This study investigated the frequency and clinical features of DYT1 in a Taiwanese dystonia cohort.
METHODS
We performed targeted next generation sequencing in 318 patients with primary dystonia. We identified one DYT1 family with various types of dystonia, and we described the clinical presentations observed in this family during a 30-year follow-up. We compared the clinical characteristics to those reported in previous studies on DYT1 from 2000 to 2020.
RESULTS
Among 318 patients, we identified only one DYT1 patient (0.3%) with an autosomal dominant family history of dystonia. The proband was a 43-year-old man that experienced progressive onset of focal lower limb dystonia from age 11 years. The disease spread caudal-rostrally to the upper limbs and cervical muscles. Prominent cervical dystonia was noted during follow-up, which was an atypical presentation of DYT1. Clinical assessments of other family members showed intrafamily variability. The proband's father and an affected sibling demonstrated only mild right-hand writer's cramp. A systematic review of previously reported DTY1 cases showed that Asian patients had a higher frequency of cervical dystonia (44.8%) than groups of Ashkenazi Jews (35%) and Non-Jewish Caucasians (30.5%) (P = 0.04).
CONCLUSION
Our findings revealed that DYT1 is rare in a Taiwanese dystonia cohort. The presentation of marked cervical dystonia could be the main feature of Asian patients with DYT1.
Topics: Adult; Child; Dystonic Disorders; Genetic Diseases, X-Linked; Humans; Male; Molecular Chaperones; Taiwan
PubMed: 34092466
DOI: 10.1016/j.jfma.2021.05.017 -
International Journal of Medical... 2021Although high-mobility group box 1 and heat-shock protein 70 are implicated in airway diseases and suggested as relevant diagnostic biomarkers, their control... (Meta-Analysis)
Meta-Analysis
Although high-mobility group box 1 and heat-shock protein 70 are implicated in airway diseases and suggested as relevant diagnostic biomarkers, their control concentrations in the airways have not yet been determined. This study aimed to evaluate concentration of healthy subjects for both these proteins in the upper and lower airways via meta-analysis. We searched MEDLINE, EMBASE, and Google Scholar for articles describing concentration of healthy subjects for these proteins. Data from healthy populations were combined using a random-effects model, and subgroup and sensitivity analyses were performed to determine between-study heterogeneity. We analyzed 22 studies involving 485 patients. Concentration of healthy subjects of high-mobility group box 1 and heat-shock protein 70 varied from "not detected" to 326.13 ng/mL and from 0.20 pg/mL to 9240.00 pg/mL, respectively, with the values showing significant heterogeneity. Subgroup analysis for high-mobility group box 1 revealed 13.63 ng/mL (95% CI 12.13-15.14), 100.31 ng/mL (95% CI -31.28-231.91), 9.54 ng/mL (95% CI 8.91-10.17), and 65.82 ng/mL (95% CI 55.51-76.14) for the lower airway, upper airway, pediatric populations, and adults, respectively, whereas that for heat-shock protein 70 revealed 20.58 pg/mL (95% CI 7.87-33.29) for the lower airway and 9240.00 ±11820 pg/mL for the upper airway. Although concentrations of healthy subjects of these proteins varied in the upper and lower airways, the levels of both these proteins were higher in the upper airway than in the lower airway, and these concentrations differed according to the age and sampling procedure. Our findings support the further evaluation of these proteins as biomarkers for airway-related diseases.
Topics: Biomarkers; HMGB1 Protein; HSP70 Heat-Shock Proteins; Healthy Volunteers; Humans; Reference Values; Respiratory Mucosa
PubMed: 33746593
DOI: 10.7150/ijms.53500 -
Medicine Jul 2022The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell...
BACKGROUND
The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML) and myeloid sarcoma (MS). Furthermore, the SET-CAN/NUP214 fusion gene has been found in the T-ALL cell line LOUCY and the AML line MEGAL. The common features of these cases are insensitivity to chemotherapy and poor prognosis. We reviewed the characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies.
METHODS
This systematic literature search was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. With the inclusion and exclusion criteria, we summarized all of the papers and performed a statistical analyses.
RESULTS
In general, the SET-CAN/NUP214 fusion gene is very rare in adult acute leukemia, more frequently found in T-ALL than in other types of leukemia, and more often in males. Flow cytometry data indicated that the markers CD34, CD33, CD13, and CD7 were common in SET-CAN/NUP214 positive acute leukemia, including ALL. Fluorescence in situ hybridization and arrays are important methods for detecting the fusion gene in newly diagnosed patients and can detect chromosomal del(9)(q34) will be detected. The chromosomal karyotype may be normal or complex, and, in terms of survival analysis, transplantation results in a better prognosis than chemotherapy alone.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
The presence of SET-CAN/NUP214 fusion gene may be a Minimal Residual Disease of early recurrence, and it might be a poor indicator of outcome.
LIMITATIONS
The mechanism, clinical characteristics, therapy and prognosis of the SET-CAN/NUP214 fusion gene in hematological malignancies require further research.
Topics: Adult; DNA-Binding Proteins; Hematologic Neoplasms; Histone Chaperones; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Male; Nuclear Pore Complex Proteins; Oncogene Proteins, Fusion; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Transcription Factors
PubMed: 35905214
DOI: 10.1097/MD.0000000000029294 -
Journal of Cancer Research and Clinical... Aug 2023Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target...
PURPOSE
Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers.
METHODS
We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease.
RESULTS
Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors.
CONCLUSION
It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade.
Topics: HSP90 Heat-Shock Proteins; Gastrointestinal Neoplasms; Humans; Molecular Targeted Therapy; Isoxazoles; Resorcinols; Antineoplastic Agents; Clinical Trials as Topic
PubMed: 36966394
DOI: 10.1007/s00432-023-04689-z -
Biomolecules Jul 2021Alzheimer's disease (AD), a progressive neurodegenerative disease, affects approximately 50 million people worldwide, which warrants the search for reliable new... (Meta-Analysis)
Meta-Analysis
Alzheimer's disease (AD), a progressive neurodegenerative disease, affects approximately 50 million people worldwide, which warrants the search for reliable new biomarkers for early diagnosis of AD. Brain-derived exosomal (BDE) proteins, which are extracellular nanovesicles released by all cell lineages of the central nervous system, have been focused as biomarkers for diagnosis, screening, prognosis prediction, and monitoring in AD. This review focused on the possibility of BDE proteins as AD biomarkers. The articles published prior to 26 January 2021 were searched in PubMed, EMBASE, Web of Science, and Cochrane Library to identify all relevant studies that reported exosome biomarkers in blood samples of patients with AD. From 342 articles, 20 studies were selected for analysis. We conducted a meta-analysis of six BDE proteins and found that levels of amyloid-β42 (standardized mean difference (SMD) = 1.534, 95% confidence interval [CI]: 0.595-2.474), total-tau (SMD = 1.224, 95% CI: 0.534-1.915), tau phosphorylated at threonine 181 (SMD = 4.038, 95% CI: 2.312-5.764), and tau phosphorylated at serine 396 (SMD = 2.511, 95% CI: 0.795-4.227) were significantly different in patients with AD compared to those in control. Whereas, those of p-tyrosine-insulin receptor substrate-1 and heat shock protein 70 did not show significant differences. This review suggested that Aβ42, t-tau, p-T181-tau, and p-S396-tau could be effective in diagnosing AD as blood biomarkers, despite the limitation in the meta-analysis based on the availability of data. Therefore, certain BDE proteins could be used as effective biomarkers for AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Brain; Exosomes; HSP70 Heat-Shock Proteins; Humans; Insulin Receptor Substrate Proteins; Peptide Fragments; tau Proteins
PubMed: 34356604
DOI: 10.3390/biom11070980 -
Acta Obstetricia Et Gynecologica... Sep 2019Progestogens are widely used for the conservative treatment of endometrial hyperplasia and early endometrial cancer. Nevertheless, they do not achieve the regression in...
INTRODUCTION
Progestogens are widely used for the conservative treatment of endometrial hyperplasia and early endometrial cancer. Nevertheless, they do not achieve the regression in all cases. Although several immunohistochemical markers have been assessed to predict the response to treatment, their usefulness is still unclear. We aimed to analyze the usefulness of each immunohistochemical marker studied in predicting the response to progestogens in endometrial hyperplasia and early endometrial cancer.
MATERIAL AND METHODS
Electronic databases were searched for relevant articles from January 2000 to June 2018. All studies assessing the association of immunohistochemical markers with the outcome of the progestogen-based therapy in endometrial hyperplasia and early endometrial cancer were included. The expression of immunohistochemical markers in pretreatment phase and changes of expression during the follow-up were evaluated in relation to response to therapy and relapse.
RESULTS
Twenty-seven studies with 1360 women were included in the systematic review; 43 immunohistochemical markers were assessed. The most studied predictive markers in the pretreatment phase were progesterone and estrogen receptors, although with conflicting results; their isoforms, and in particular progesterone receptor B, appeared more promising. Further studies are needed to confirm the usefulness of mismatch repair proteins, Dusp6, GRP78 and PTEN combined with other molecules such as phospho-AKT or phospho-mTOR. In the follow-up phase, Nrf2 and survivin showed the stronger evidence; a role may also be played by Bcl2 and Ki67. Further studies are necessary for Fas, NCoR, AKR1C1, HE4, PAX2 and SPAG9.
CONCLUSIONS
Several immunohistochemical markers might be helpful in predicting the response to conservative treatment of endometrial hyperplasia and early endometrial cancer on pretreatment and follow-up specimens. Further studies are needed to confirm their usefulness and possibly integrate them in a predictive immunohistochemical panel.
Topics: Biomarkers, Tumor; Conservative Treatment; Endometrial Hyperplasia; Endometrial Neoplasms; Endoplasmic Reticulum Chaperone BiP; Female; Humans; Immunohistochemistry; Predictive Value of Tests; Progestins
PubMed: 30793281
DOI: 10.1111/aogs.13587