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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F21%3AN0000035" target="_blank" >RIV/00064190:_____/21:N0000035 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/21:43921952 RIV/00216208:11110/21:10430533 RIV/00064165:_____/21:10430533 RIV/00064173:_____/21:N0000044

Výsledek na webu

<a href="http://dx.doi.org/10.3390/cancers13174407" target="_blank" >http://dx.doi.org/10.3390/cancers13174407</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers13174407" target="_blank" >10.3390/cancers13174407</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Simple Summary Heat shock proteins (HSPs) are cytoprotective chaperones occurring in virtually all living organisms including various types of cancer cells to repair proteotoxic damage. Some of HSPs influence tumor prognosis and represent promising therapeutic targets. To clarify prognostic significance of HSPs 27, 70, and 110 in colorectal carcinoma, we retrospectively performed HSP immunohistochemistry on tissue microarrays from archive tumor tissue from 297 patients. Survival analysis revealed significantly shorter overall survival (OS) and borderline insignificantly shorter cancer specific survival (CSS) in patients with HSP70+ tumors. In HSP27+, both OS and CSS were insignificantly shorter. HSP110 showed no influence on survival. We found an association of HSP27 and HSP70 expression with advanced cancer stage. In multivariate analysis, only advanced stage and right sided localization were independent predictors of worse survival, whereas all three examined HSPs were insignificant. In conclusion, from all three HSPs examined in our study, only HSP70 had an impact on colorectal cancer prognosis, although it is stage-dependent. 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

Simple Summary Heat shock proteins (HSPs) are cytoprotective chaperones occurring in virtually all living organisms including various types of cancer cells to repair proteotoxic damage. Some of HSPs influence tumor prognosis and represent promising therapeutic targets. To clarify prognostic significance of HSPs 27, 70, and 110 in colorectal carcinoma, we retrospectively performed HSP immunohistochemistry on tissue microarrays from archive tumor tissue from 297 patients. Survival analysis revealed significantly shorter overall survival (OS) and borderline insignificantly shorter cancer specific survival (CSS) in patients with HSP70+ tumors. In HSP27+, both OS and CSS were insignificantly shorter. HSP110 showed no influence on survival. We found an association of HSP27 and HSP70 expression with advanced cancer stage. In multivariate analysis, only advanced stage and right sided localization were independent predictors of worse survival, whereas all three examined HSPs were insignificant. In conclusion, from all three HSPs examined in our study, only HSP70 had an impact on colorectal cancer prognosis, although it is stage-dependent. 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

CANCERS

ISSN

2072-6694

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

15

Strana od-do

Article Number 4407

Kód UT WoS článku

000694134500001

EID výsledku v databázi Scopus

2-s2.0-85114046981