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

included in the study. These collective findings emphasize exhibited different effect sizes. This regional difference may
the potential role for SIRT1 in cancer progression and be attributed to genetic and environmental factors that
prognosis, reinforcing the importance of understanding influence cancer biology across different ethnic groups, as
its impact on various cancers. Finally, our findings align previously defined by Sun et al. 17
with Zhou et al., who examined the distinct associations The overrepresentation of Asian studies in our meta-
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between specific cancers and SIRT1 expression. While analysis could affect the generalizability of the findings.
our analysis focused on SIRT1, their research emphasized In Asian populations, dietary, lifestyle, and genetic
SIRT3, exhibiting its diverse impact across different cancer predispositions may affect tumorigenesis, and the role
types. They found SIRT3 to be an unfavorable prognostic of SIRT1 as a regulator of cancer progression could be
factor in breast, colon, and non-small-cell lung cancers, more pronounced. Moreover, environmental and lifestyle
but a favorable factor in chronic lymphocytic leukemia, factors prevalent in Asian populations may differ from
hepatocellular carcinoma, pancreatic cancer, and renal cell those in non-Asian populations, which may limit the
carcinoma. These varying prognostic roles of SIRT3 across applicability of our results to other regions. This imbalance
cancers echo the specific associations that we observed
between SIRT1 and different cancer types in our study. potentially skews the global prognostic significance of
SIRT1. To enhance generalizability, future studies should
The findings from all these studies confirm the include a more diverse set of populations to account
significant prognostic role of SIRT1 across various cancers, for regional variations in cancer biology and SIRT1
despite some discrepancies in specific cancer types and expression. The inclusion of a higher number of studies
regional differences. For example, our analysis shows non- from Asia, particularly China, in our meta-analysis, may
significant correlations in colorectal and breast cancers. have contributed to the observed differences in effect sizes.
The lack of significant correlations in colorectal cancer This limitation highlights the need for further research in
may stem from the complexity of tumorigenesis, where diverse populations, especially in non-Asian cohorts, to
multiple genetic and epigenetic pathways overshadow the better understand how SIRT1 expression correlates with
impact of SIRT1 expression. SIRT1 regulation in colorectal cancer prognosis globally.
cancer involves genetic interactions with the Vitamin D
receptor, which enhances SIRT1 expression in response While Egger’s test and trim-and-fill analysis indicated
to 1,25-dihydroxyvitamin D3, as well as epigenetic no significant publication bias, the observed funnel
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modifications like acetylation at lysine 610, which plot asymmetry and bubble plot suggested the potential
boosts its deacetylase activity. In addition, microRNA influence of underlying factors. Specifically, the aggregation
7
regulation and the role of E3 ubiquitin ligases have of studies with larger standard errors near the base of the
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notable impact on SIRT1 expression in colorectal cancer. funnel plot reflects selective reporting of smaller studies
Previous studies have suggested that factors such as with more positive findings. Although the non-significant
microsatellite instability, chromosomal instability, intercept from Egger’s test and the absence of imputed
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and mutations in key oncogenes and tumor suppressor studies in trim-and-fill analysis reinforce the robustness of
genes (e.g., adenomatous polyposis coli [APC], Kirsten the effect size, this asymmetry warrants further scrutiny.
rat sarcoma virus [KRAS], and p53 tumor suppressor Factors such as study design, regional differences, or
protein [TP53]) might dominate the prognosis in selective reporting of positive results may contribute to
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colorectal cancer, potentially diminishing the prognostic this asymmetry, necessitating caution in interpreting the
relevance of SIRT1. Similarly, breast cancer encompasses overall findings.
various subtypes (e.g., hormone receptor-positive, human Mechanistically, SIRT1 is a nicotinamide adenine
epidermal growth factor receptor 2 [HER2]-positive, and dinucleotide (NAD )-dependent deacetylase that influences
+
triple-negative), each with distinct molecular profiles. cancer progression through various pathways. Specifically,
The role of SIRT1 may vary across these subtypes, and the SIRT1 undergoes post-translational modifications,
single breast cancer study included in our analysis may not including covalent linking to interferon-stimulated genes
have had sufficient statistical power to detect the subtype- (ISGs). SIRT1 and ISGs have been found to colocalize
specific effects of SIRT1. in cellular compartments such as the nucleus and
An important aspect revealed by our subgroup analyses mitochondria, promoting physical interactions between
is the variation in the prognostic value of SIRT1 between various proteins. The ISGylation of SIRT1 can enhance its
Asian and non-Asian populations. Studies conducted in deacetylase enzymatic function by disassociating it from
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Asian populations, particularly in China, consistently inhibitory proteins. This regulatory mechanism has been
demonstrated significant prognostic effects of SIRT1, while implicated in lung cancer progression and may diminish the
the results in non-Asian populations, though significant, efficacy of deoxyribonucleic acid-damaging treatments.
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Volume 4 Issue 1 (2025) 10 doi: 10.36922/gpd.4294