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

Elevated levels of SIRT1 have also been linked to resistance and patient survival. Our meta-analysis, along with other
to chemotherapy and radiotherapy in ESCC. Morishita studies, demonstrates that elevated SIRT1 expression is
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et al. demonstrated the potential of SIRT1 as a predictive associated with poorer outcomes across various cancer
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marker for therapeutic response, showing that reducing types, making it a potential prognostic biomarker. A key
SIRT1 levels through knockdown enhances sensitivity to contribution of this study is its application in clinical
treatment in ESCC. Further, Mvunta et al. showed that settings, where SIRT1 could help predict patient outcomes
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increased levels of SIRT1 are associated with elevated and guide treatment decisions. Identifying SIRT1 as a
tumor aggressiveness. This relationship involves SIRT1 modulator of tumorigenesis suggests its potential utility
downregulating p53 and miR-101, while upregulating the in precision medicine, enabling personalized strategies
KPNA3 axis, thereby promoting proliferation and invasive aimed at inhibiting SIRT1 activity to enhance patient
metastasis in colorectal cancer. In addition, in renal clear survival. Understanding the molecular mechanisms of
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cell carcinoma, elevated SIRT1 expression is associated SIRT1, particularly its interactions with pathways like p53
with poor prognosis and is linked to lipid metabolism and and epigenetic modifications, provides valuable insights
immune infiltration. These findings highlight the role of for therapeutic intervention. Future research should focus
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SIRT1 in modulating the tumor microenvironment and its on developing SIRT1 inhibitors or modulators to improve
potential as a target for therapeutic strategies. cancer treatments by sensitizing tumors to chemotherapy
and radiotherapy or by targeting SIRT1-specific pathways.
In a clinical context, targeting SIRT1 in cancer therapy Integrating SIRT1-based biomarkers into precision
shows promise. Inhibition of SIRT1 enhances p53 medicine could enable tailored therapies, optimizing
acetylation, thereby increasing apoptosis and reducing treatment plans based on individual tumor profiles and
cell proliferation, while potential inhibitors such as SIRT1 expression levels, ultimately improving patient
Doxercalciferol and Timiperone have demonstrated outcomes.
efficacy in various cancer models. However, the context-
dependent role of SIRT1 complicates its therapeutic 5. Conclusion
targeting, as it may also promote tumor growth at certain
stages of cancer development. The comprehensive meta-analysis, which pooled results
from 15 studies involving 3059 cases, predominantly from
While this meta-analysis provides valuable insights, Asian populations, underscores the strong and consistent
several limitations warrant consideration. The reliance on positive prognostic value of SIRT1 across various cancers.
existing studies, predominantly from Asia, may introduce The absence of significant variability in our analysis
inherent biases or exclusions that potentially affect the (I² = 0.00) further supports the stable impact of SIRT1
overall analysis. This imbalance between Asian and non- across different study variables, reinforcing its prognostic
Asian populations limits the generalizability of our findings, significance. Our findings align with previous research,
highlighting the potential bias in the prognostic significance demonstrating that the influence of SIRT1 transcends
of SIRT1 across different regions. Future studies should geographical and demographic boundaries, emphasizing
focus on non-Asian populations with varying genetic, its critical role in cancer prognosis. By synthesizing data
environmental, and lifestyle factors. Further investigation from multiple studies, our meta-analysis highlights the
into SIRT1 expression and its role as a prognostic marker consistent association between elevated SIRT1 expression
is particularly warranted in breast and colorectal cancers, and poorer outcomes, reinforcing its relevance as a
which are influenced by multiple genetic, epigenetic, and prognostic factor. These insights pave the way for future
environmental factors, as discussed earlier. Although Egger’s research on SIRT1 as a therapeutic target, particularly in
test and trim-and-fill analysis indicated no significant aggressive cancers such as gastrointestinal cancers and
publication bias, the observed asymmetry in the funnel hepatocellular carcinoma.
plots suggests a higher likelihood of publication bias in Future investigations should focus on the mechanistic
smaller studies with positive findings. Therefore, study role of SIRT1 in cancer progression and its interaction with
design, regional differences, and other moderators should other prognostic factors to enhance targeted interventions.
be assessed for further scrutiny. In addition, the duration Specifically, developing SIRT1 inhibitors or modulators as
of patient follow-up in individual studies may impact the therapeutic agents could significantly improve treatment
evaluation of long-term prognostic effects, underscoring the strategies for certain cancer types. In addition, research
need for more extensive investigations to comprehensively should aim to identify biomarkers that predict the efficacy
understand SIRT1’s role over varying time frames. of SIRT1-targeted therapies, facilitating precision medicine
The clinical significance of SIRT1 lies in its role in approaches tailored to individual patient profiles. These
cancer progression, influencing tumor growth, metastasis, efforts would not only deepen our understanding of the

Volume 4 Issue 1 (2025) 11 doi: 10.36922/gpd.4294