Page 131 - EJMO-9-3

Eurasian Journal of
Medicine and Oncology KRAS TP53 cholangiocarcinoma

closely associated with tumorigenesis, with approximately with “survival,” “prognosis,” or “outcome” to identify
one-third of tumors harboring Ras mutations. TP53, a key studies specifically addressing the impact of these genetic
player in DNA damage repair and apoptosis, contributes mutations on patient outcomes. The search strategy was
to cancer development when mutated. Recent studies designed to be broad yet focused, aiming to capture all
have explored KRAS and TP53 mutations as potential relevant studies that contribute to understanding the
targets for cancer therapy. Clinically, Zheng et al. found relationship between these mutations and survival in
8
9
that colorectal cancer patients with KRAS mutations had cholangiocarcinoma.
significantly shorter survival. In another study involving Two independent researchers conducted the literature
272 hepatocellular carcinoma patients treated with search to minimize bias and ensure accuracy. Both
transarterial embolization, those with TP53 mutations researchers followed the same predefined search strategy,
exhibited poorer survival outcomes. 10
and the search was performed twice to confirm consistency.
In the context of cholangiocarcinoma, current studies In addition, the reference lists of the included articles were
suggest that approximately 30% of patients carry KRAS manually reviewed to identify any additional studies not
mutations, and sequencing of 382 cholangiocarcinoma captured by the database search. This approach ensured that
11
cases revealed TP53 mutations in 51.6% of patients. the literature search was exhaustive and comprehensive,
12
Additional cholangiocarcinoma studies have also capturing as many relevant studies as possible.
reported a strong correlation between KRAS or TP53
mutation phenotypes and patient prognosis. 13,14 However, The inclusion criteria for studies are as follows:
despite these findings, the existing research does not yet (1) studies investigating the relationship between
KRAS and TP53 gene mutations and prognosis in
provide definitive evidence on the specific mechanisms cholangiocarcinoma patients; (2) studies reporting
and prognostic impact of KRAS and TP53 mutations in survival outcomes, including odds ratios (ORs), hazard
cholangiocarcinoma. Given this background, we believe ratios (HRs), or sufficient data to compute these values;
that a meta-analysis of the available studies is necessary.
Such an analysis will help integrate data from various and (3) studies clearly identifying human populations
studies and provide a comprehensive assessment of the and providing demographic information, such as age and
prognostic significance of KRAS and TP53 mutations in sex, along with relevant clinical data. These criteria were
cholangiocarcinoma, thereby offering stronger scientific designed to ensure the inclusion of studies with a focused
evidence for future clinical decisions and research scope and adequate detail for meaningful analysis.
directions. Through a comprehensive meta-analysis, we Exclusion criteria were applied to ensure the quality
aim to elucidate the relationship between KRAS and TP53 and relevance of the selected studies. These criteria are
mutations and survival outcomes in cholangiocarcinoma, as follows: (1) non-English or non-Chinese literature
and further explore the potential of these genetic mutations was excluded to ensure uniformity and the ability to
as key molecular biomarkers for prognosis and treatment assess studies based on widely recognized and accessible
planning. languages; (2) reviews, conference papers, case reports,
clinical trials, animal studies, and cell/molecular studies
2. Materials and methods were excluded as they did not directly address the prognosis
A systematic and comprehensive literature search was of human cholangiocarcinoma patients harboring KRAS
conducted across several well-established public databases and TP53 mutations; (3) studies lacking relevant survival
to identify relevant studies. The databases searched included data, such as OR, HR, or survival times, were excluded
PubMed, Web of Science, Cochrane Library, Embase, as these metrics are crucial for assessing the relationship
China National Knowledge Infrastructure (CNKI), and between mutations and prognosis; (4) studies with a high
Wanfang Data, providing a broad representation of both risk of bias, such as those with unclear methodologies,
international and Chinese research. The search was limited incomplete data reporting, or inadequate control of
to studies published up to April 2025 to ensure the inclusion confounding factors, were excluded to preserve validity;
of the most up-to-date studies on KRAS and TP53 mutations and (5) studies with short-term follow-up periods were
in cholangiocarcinoma. To ensure thorough coverage, excluded, as the analysis focused on long-term survival
the following search terms were used: “TP53 gene” or outcomes.
“KRAS gene” combined with “cholangiocarcinoma” 2.1. Data extraction and systematic evaluation
or “bile duct cancer,” further expanded to include
“intrahepatic cholangiocarcinoma,” “cholangiocellular Data extraction was independently performed by two
carcinoma,” “extrahepatic cholangiocarcinoma,” and “hilar researchers following a standardized and rigorous protocol
cholangiocarcinoma.” These terms were then combined to ensure accuracy and clarity of all extracted data.

Volume 9 Issue 3 (2025) 123 doi: 10.36922/EJMO025120063