The Prognostic Significance of Hsp70 in Patients with Colorectal Cancer Patients: A PRISMA-Compliant Meta-Analysis

Gao, Guangyu; Liu, Songtao; Yao, Zhen; Zhan, Yan-yan; Chen, Wenyue; Liu, Yulong

doi:10.1155/2021/5526327

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…Concerning CRC, the HSP70 overexpression has been described in comparison to non-neoplastic large bowel mucosa [60]. With a focus on impact on survival, a recent meta-analysis of nine studies presented worse prognosis in CRCs expressing HSP70, in line with our results [61]. Bauer et al, as above-mentioned, found HSP70 to be an unfavorable prognostic predictor, in line with our findings.…”

Section: Discussionsupporting

confidence: 92%

Heat Shock Proteins 27, 70, and 110: Expression and Prognostic Significance in Colorectal Cancer

Hrudka

Jelínková

Fišerová

et al. 2021

Cancers

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Heat shock proteins (HSPs) are evolutionarily conserved chaperones occurring in virtually all living organisms playing a key role in the maintenance of cellular homeostasis. They are constitutively expressed to prevent and repair protein damage following various physiological and environmental stressors. HSPs are overexpressed in various types of cancers to provide cytoprotective function, and they have been described to influence prognosis and response to therapy. Moreover, they have been used as a tumor marker in blood serum biochemistry and they represent a potentially promising therapeutic target. To clarify prognostic significance of two canonical HSPs (27 and 70) and less known HSP110 (previously known as HSP105) in colorectal carcinoma (CRC), we retrospectively performed HSP immunohistochemistry on tissue microarrays from formalin-fixed paraffin-embedded tumor tissue from 297 patients with known follow-up. Survival analysis (univariate Kaplan–Meier analysis with the log-rank test and multivariate Cox regression) revealed significantly shorter overall survival (OS, mean 5.54 vs. 7.07, p = 0.033) and borderline insignificantly shorter cancer specific survival (CSS, mean 6.3 vs. 7.87 years, p = 0.066) in patients with HSP70+ tumors. In the case of HSP27+ tumors, there was an insignificantly shorter OS (mean 6.36 vs. 7.13 years, p = 0.2) and CSS (mean 7.17 vs. 7.95 years, p = 0.2). HSP110 showed no significant impact on survival. Using Pearson’s chi-squared test, there was a significant association of HSP27 and HSP70 expression with advanced cancer stage. HSP27+ tumors were more frequently mismatch-repair proficient and vice versa (p = 0.014), and they occurred more often in female patients and vice versa (p = 0.015). There was an enrichment of left sided tumors with HSP110+ compared to the right sided (p = 0.022). In multivariate Cox regression adjusted on the UICC stage, grade and right/left side; both HSPs 27 and 70 were not independent survival predictors (p = 0.616 & p = 0.586). In multivariate analysis, only advanced UICC stage (p = 0) and right sided localization (p = 0.04) were independent predictors of worse CSS. In conclusion, from all three HSPs examined in our study, only HSP70 expression worsened CRC prognosis, although stage-dependent. The contribution of this article may be seen as a large survival analysis of HSPs 27 and 70 and the largest analysis of HSP110 described in CRC.

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Section: Discussionsupporting

confidence: 92%

Heat Shock Proteins 27, 70, and 110: Expression and Prognostic Significance in Colorectal Cancer

Hrudka

Jelínková

Fišerová

et al. 2021

Cancers

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“…Consistently, it is overexpressed in number of cancers, although clinical data regarding CRC are, as observed by Gao at al. [37], surprisingly scanty. Lazaris et al [38] showed 77% of colorectal tumor samples to Oxicams downregulated expression of HSP90AA1 gene more markedly than protein: compounds #2-5 in Caco-2 cells and compounds #1-5 in HCT 116 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Consistently, it is overexpressed in number of cancers, although clinical data regarding CRC are, as observed by Gao at al. [ 37 ], surprisingly scanty. Lazaris et al [ 38 ] showed 77% of colorectal tumor samples to contain at least 10% of neoplastic cells with Hsp70-immunoreactivity.…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring

et al. 2021

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Heat shock proteins HSPA1/Hsp70α and HSP90AA1/Hsp90α are crucial for cancer growth but their expression pattern in colorectal polyps or whether they can be modulated by oxicams is unknown. We quantified (RTqPCR) HSPA1 and HSP90AA1 expression in 50 polyp-normal pairs in relation to polyp malignancy potential and examined the effect of piroxicam, meloxicam and five novel analogues on HSPA1 and HSP90AA1 expression (mRNA/protein) in colorectal adenocarcinoma lines. HSPA1 and HSP90AA1 were upregulated in polyps by 3- and 2.9-fold. Expression ratios were higher in polyps with higher dysplasia grade and dominant villous growth pattern, mostly a result of diminished gene expression in normal tissue. Classic oxicams had negligible/non-significant effect on HSP expression. Their most effective analogue inhibited HSPA1 protein and gene by 2.5-fold and 5.7-fold in Caco-2 and by 11.5-fold and 6.8-fold in HCT116 and HSPA1 protein in HT-29 by 1.9-fold. It downregulated HSP90AA1 protein and gene by 1.9-fold and 3.7-fold in Caco-2 and by 2-fold and 5.0-fold in HCT116. HSPA1 and HSP90AA1 are upregulated in colorectal polyps reflecting their potential for malignancy. HSPA1 in cancer cells and, to lesser degree, HSP90AA1 can be reduced by oxicam analogues with thiazine ring substituted via propylene linker by arylpiperazine pharmacophore with fluorine substituents and by benzoyl moiety.

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“…Therefore, understanding the mechanisms and consequences of the interaction is essential. A potential key player of the crosstalk in the tumor microenvironment may be HSP70, which is overexpressed in cancer compared to normal tissue [ 2 , 79 , 80 , 81 , 82 ]. The expression was shown to be correlated to tumor grade, therapy resistance, and worse overall survival [ 80 , 81 , 82 , 83 , 84 , 85 ].…”

Section: Role Of Exhsp70: Regulation Of Immune Responsesmentioning

confidence: 99%

“…A potential key player of the crosstalk in the tumor microenvironment may be HSP70, which is overexpressed in cancer compared to normal tissue [ 2 , 79 , 80 , 81 , 82 ]. The expression was shown to be correlated to tumor grade, therapy resistance, and worse overall survival [ 80 , 81 , 82 , 83 , 84 , 85 ]. In particular, HSP70 can inhibit the intrinsic and extrinsic apoptotic pathway and block oncogene-induced senescence, resulting in therapy resistance [ 2 ].…”

Section: Role Of Exhsp70: Regulation Of Immune Responsesmentioning

confidence: 99%

The Role of Extracellular HSP70 in the Function of Tumor-Associated Immune Cells

Linder

Strandmann

2021

Cancers

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Extracellular vesicles released by tumor cells (T-EVs) are known to contain danger-associated molecular patterns (DAMPs), which are released in response to cellular stress to alert the immune system to the dangerous cell. Part of this defense mechanism is the heat shock protein 70 (HSP70), and HSP70-positive T-EVs are known to trigger anti-tumor immune responses. Moreover, extracellular HSP70 acts as an immunogen that contributes to the cross-presentation of major histocompatibility complex (MHC) class I molecules. However, the release of DAMPs, including HSP70, may also induce chronic inflammation or suppress immune cell activity, promoting tumor growth. Here, we summarize the current knowledge on soluble, membrane-bound, and EV-associated HSP70 regarding their functions in regulating tumor-associated immune cells in the tumor microenvironment. The molecular mechanisms involved in the translocation of HSP70 to the plasma membrane of tumor cells and its release via exosomes or soluble proteins are summarized. Furthermore, perspectives for immunotherapies aimed to target HSP70 and its receptors for cancer treatment are discussed and presented.

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The Prognostic Significance of Hsp70 in Patients with Colorectal Cancer Patients: A PRISMA-Compliant Meta-Analysis

Cited by 9 publications

References 33 publications

Heat Shock Proteins 27, 70, and 110: Expression and Prognostic Significance in Colorectal Cancer

Heat Shock Proteins 27, 70, and 110: Expression and Prognostic Significance in Colorectal Cancer

Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring

The Role of Extracellular HSP70 in the Function of Tumor-Associated Immune Cells

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