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Gene & Protein in Disease Prognostic role of SIRT1 expression in cancer

7 Faculty of Basic Medical Subjects, Shu-Qing Medical College of Zhengzhou, Zhengzhou, Henan, China
8 Department of Medicine, Huaxian County People’s Hospital, Huaxian, Henan, China

1. Introduction reached a different conclusion, suggesting that higher
SIRT1 expression may improve survival. This ongoing
Sirtuin 1 (SIRT1), a member of the sirtuin family, has controversy remains about whether SIRT1 overexpression
attracted considerable attention due to its regulatory predicts good or poor prognosis highlights the need
impact on various cellular pathways. It is the most well- for a more robust analysis. Most evidence supports that
studied isoform among the sirtuin family members, view that overexpressed SIRT1 negatively affects cancer
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which are involved in regulating a wide range of diseases, prognosis. 21-23 These conflicting results underscore the need
including stress responses, apoptosis, and gene stability. for a comprehensive investigation to better understand the
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2
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This extensive influence positions SIRT1 as a key player in true role of SIRT1 in cancer progression.
cancer progression and development.
Therefore, this study aims to assess the prognostic
Although the sirtuin family comprises several
members, the focus on SIRT1 stems from its prevalence significance of SIRT1 expression across various cancer
types, synthesizing existing findings to provide a clearer
and prominent role in maintaining cellular homeostasis. understanding of its impact on cancer prognosis in different
5,6
Its unique enzymatic activity and significant involvement malignancies and geographical regions. Furthermore, this
in crucial cellular processes distinguish it from other paper seeks to offer insights into the potential clinical
family members, warranting dedicated exploration. implications of SIRT1 expression for cancer patients.
Studies have highlighted both tumor-suppressive and
tumor-promoting roles for SIRT1. For instance, SIRT1 2. Methods
can promote tumorigenesis by deacetylating p53, which
leads to the downregulation of p53 and the upregulation of 2.1. Search strategy
karyopherin subunit alpha 3 (KPNA3) through modulation Our meta-analysis follows the Preferred Reporting Items
of microRNA (miR)-101. This cascade enhances tumor cell for Systematic Reviews and Meta-Analyses guidelines. The
survival, migration, chemoresistance, and proliferation in authors – MI, ST, and SA – conducted a comprehensive
colorectal cancer. In addition, SIRT1 supports epithelial- independent search for relevant studies and retrieved
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to-mesenchymal transition, which facilitates metastasis in references from Google Scholar, PubMed, and Web of
various tumor types. However, SIRT1 also exhibits tumor- Science using a range of keywords, such as “SIRT1,”
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suppressive effects by maintaining genomic stability “cancer,” “prognosis,” and “survival” (Supplementary File
and regulating oxidative stress responses. The balance for detailed search strategy). The time window spanned
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between these roles depends on the specific context. For from January 2015 to November 2023. All retrieved
example, in lung cancer, SIRT1 inhibits autophagy in references were processed in EndNote v21.2 (Clarivate) for
cancer cells, thereby reducing cell proliferation, invasion, screening.
and migration. 10
2.2. Inclusion and exclusion criteria
The current body of research on SIRT1 in cancer
prognosis, spanning from 2012 to 2023, reveals The retrieved studies were deduplicated and screened by
inconsistencies. SIRT1 is elevated in ovarian cancer, reviewing titles, abstracts, types of articles, and the language
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gastric cancer, liver cancer, and breast cancer. While of publication independently by three authors – UAKS,
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previous meta-analyses have examined the prognostic FI, and KM. Original research studies that specifically
significance of SIRT1, they have largely focused on reported the prognostic role of SIRT1 in various human
Asian populations, specific cancer types, or older cancers, published in English, and included all necessary
publications. 15-17 For instance, SIRT1 expression has been details, were included by MI and ST. Studies were excluded
associated with poor overall survival (OS) and disease- if they were not original research articles (e.g., reviews,
free survival in breast cancer. In esophageal squamous commentaries, conference abstracts, and protocols),
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cell carcinoma (ESCC), high SIRT1 expression correlates focused on the role of SIRT1 in areas unrelated to cancer,
with advanced tumor stages and poor prognosis. 18,19 A or were conducted using animal models. In addition,
broader meta-analysis encompassing multiple cancer studies published in non-English languages or those
types has shown that elevated SIRT1 levels consistently lacking essential data were excluded from the study. Any
predict worse survival outcomes and are associated with discrepancies during the screening process were discussed
tumor progression. However, a study by Jung et al. and resolved by the corresponding authors, AA and MBK.
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Volume 4 Issue 1 (2025) 2 doi: 10.36922/gpd.4294