Page 137 - EJMO-9-3

Eurasian Journal of
Medicine and Oncology KRAS TP53 cholangiocarcinoma

by lung cancer subtype. Similarly, different subtypes of
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cholangiocarcinoma – such as ICC and ECC – exhibit
distinct genetic mutation profiles. ECC patients are more
likely to harbor KRAS and TP53 mutations, whereas ICC
patients more commonly present with IDH1 mutations.
These differences may reduce the predictive accuracy of
unified prognostic models across subtypes. 37,38 Therefore,
developing subtype-specific prognostic models based on
unique mutation profiles may significantly enhance clinical
applicability and accuracy. This has become an active area
of research. 39,40 Although our study employed a unified
prognostic model, recognizing the different roles that
KRAS and TP53 mutations play in each subtype highlights
the need for subtype-specific tools. A one-size-fits-all
Figure 5. Sensitivity analysis of TP53 studies approach may overlook meaningful distinctions, whereas
Abbreviation: CI: Confidence interval. subtype-tailored models could offer more accurate,
personalized prognostic assessments.
treatment of cholangiocarcinoma. Due to factors such as liver fluke infection and
It is noteworthy that in the treatment of consumption of undercooked fish, regions including
cholangiocarcinoma, immunotherapy – as an emerging northeastern Thailand, Korea, and Japan are considered
therapeutic approach – has shown promising results. 26,27 high-risk areas for cholangiocarcinoma. 41-43 However,
KRAS and TP53 mutations, two common oncogenic because of the limited number of eligible studies from these
drivers, have been shown to influence immune evasion regions, they were not included in our analysis. While the
mechanisms in various cancer types, which may higher incidence rates in these areas did not conflict with
significantly affect responses to immunotherapy. 28-30 our search criteria, the lack of regional representation
Several studies have demonstrated that KRAS and TP53 may affect the comprehensiveness of our findings. Future
co-mutations are associated with a significant increase research should prioritize incorporating data from these
in PD-L1 expression, along with higher tumor burden high-risk regions to further validate the prognostic
and immune cell infiltration. 31,32 Two studies on lung significance of KRAS and TP53 mutations. In addition,
adenocarcinoma found that patients with KRAS and TP53 due to the insufficient number of eligible studies, we were
co-mutations responded better to immune checkpoint unable to conduct subgroup analyses based on treatment
inhibitors. 33,34 In cholangiocarcinoma, Chen et al. modalities (e.g., chemotherapy and immunotherapy) or
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observed differing clinical benefits between patients mutation types (KRAS only, TP53 only, or co-mutations).
Furthermore, data limitations prevented adjustments
with only KRAS mutations and those with both KRAS for confounding variables such as tumor location (hilar,
and TP53 co-mutations receiving immunotherapy. intrahepatic, or extrahepatic) or stage. Finally, this study
Specifically, patients with KRAS mutations alone exhibited only included published literature, excluding unpublished
poor responses to immunotherapy, whereas those with studies with negative results. Future investigations are
KRAS-TP53 co-mutations demonstrated elevated PD-L1 needed to validate and expand upon the prognostic effects
expression and greater immune cell infiltration. Among of KRAS and TP53 mutations in cholangiocarcinoma
all genetic subgroups, cholangiocarcinoma patients with patients.
various combinations of KRAS and TP53 mutations
achieved the highest objective response rates following 5. Conclusion
immunotherapy. 35
Cholangiocarcinoma is a highly heterogeneous malignant
In our study, we analyzed the relationship between tumor, with KRAS and TP53 gene mutations playing
KRAS and TP53 mutations and survival prognosis a crucial role in its occurrence and development. Our
in cholangiocarcinoma patients. However, with the findings indicate that mutations in KRAS and TP53 are
advancement in molecular biology, growing evidence each independently associated with poor prognosis in
suggests significant differences in the mutation profiles cholangiocarcinoma patients. However, existing studies
of various cancer subtypes, which may influence the exhibit certain biases and heterogeneity. Therefore,
clinical applicability of prognostic models. For instance, further high-quality research is essential to validate and
a study found that the prognostic value of TROP2 varies refine these conclusions, ultimately contributing to more

Volume 9 Issue 3 (2025) 129 doi: 10.36922/EJMO025120063