Page 132 - EJMO-9-3

Eurasian Journal of
Medicine and Oncology KRAS TP53 cholangiocarcinoma

This systematic approach minimized human error and critical insights into the strength of the association between
maintained the integrity of the meta-analysis by ensuring mutations and prognosis.
that data were comparable across the included studies. To The reliability of the included studies was further
maintain transparency and traceability, all information assessed by two researchers using the Newcastle–Ottawa
obtained during the data extraction process was archived, Scale, a widely used tool for assessing the quality of non-
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and a clear record was kept of each step taken. This randomized studies in meta-analyses. This scale evaluates
archived data allowed for easy retrieval and verification three key areas of study quality: outcome assessment,
of the information, thereby ensuring the robustness comparability, and selection criteria. Outcome assessment
of the meta-analysis. In cases where disagreements or included evaluating whether the inclusion and exclusion
uncertainties arose during the data extraction process, they criteria were clearly defined, whether the follow-up period
were resolved through consensus, with the involvement of was sufficient to capture long-term outcomes, whether
a third reviewer to provide an objective resolution. This loss to follow-up significantly biased the study results, and
ensured that any potential biases were minimized, and all whether outcome measurements for survival and disease
discrepancies were thoroughly addressed to maintain the progression were robust and valid. Comparability was
accuracy of the data. The third reviewer acted as a neutral assessed based on the availability of sufficient clinical data to
party, ensuring that decisions were made based on clear support group comparisons, including patient characteristics
and consistent criteria. such as age, sex, and pathological features. The studies
The following data were extracted from the included were also evaluated on whether they were appropriately
studies: (1) the first author’s name to identify the primary controlled for potential confounders, such as TNM staging
author and the study reference; (2) the year of publication and treatment methods, and whether the control groups
to determine the recency of the study; (3) the country were appropriately selected and analyzed. Selection criteria
where the study was conducted to understand the assessed the representativeness of the exposed cohort,
geographic distribution of the study participants; (4) the considering whether the study population accurately
number of patients included to gauge the sample size and reflected the broader population of cholangiocarcinoma
statistical power of the study; (5) the race of the patient to patients. The selection of the unexposed cohort was also
identify any racial differences in the study population that evaluated to determine whether it was comparable to the
could influence genetic variation and prognosis; (6) tumor exposed cohort. We further assessed the scientific validity of
location to determine whether intrahepatic, extrahepatic, the exposure factor analysis, verifying that KRAS and TP53
or hilar cholangiocarcinoma impacted prognosis; (7) mutations were correctly identified and properly attributed.
study design to classify the type of study (e.g., cohort or Each study was assigned a score based on these criteria,
case–control) and to assess its potential bias and validity; with a maximum possible score of 9. The total score was
(8) treatment methods to evaluate whether treatment used to evaluate the methodological quality of each study
regimens were consistent across studies; (9) detection and to ensure that only studies with sufficient rigor were
methods for KRAS and TP53 gene mutations; (10) the included in the meta-analysis. This process enhanced the
status KRAS and TP53 genes (i.e., wild-type or mutated); reliability and scientific rigor of the meta-analysis results,
(11) definitions of cutoff points to determine how minimized the risk of bias, and strengthened the validity
thresholds for genetic mutations or prognostic factors were of the findings.
defined; and (12) follow-up time to ensure it was adequate
to capture meaningful survival outcomes. 2.2. Statistical analysis
In addition, tumor clinical and pathological parameters To assess the relationship between KRAS mutations, TP53
were extracted, including tumor size, number of tumors, mutations, and survival outcomes in cholangiocarcinoma
lymph node metastasis, distant metastasis, tumor patients, HRs and their corresponding 95% CIs were
differentiation, and TNM staging, as these are crucial for collected from each of the included studies. The HR is
understanding cancer progression and prognosis. Survival a commonly used measure to quantify the effect of a
outcomes such as overall survival (OS) or disease-free particular variable (in this case, KRAS or TP53 mutations)
survival (DFS) were recorded as the primary endpoints on survival, with values >1 indicating an increased risk,
for assessing the impact of genetic mutations on patient and values <1 suggesting a protective effect. The 95% CI
prognosis. In addition, the results of univariate and offers an estimate of the precision of the HR, with wider
multivariate analyses for both OS and median survival intervals indicating greater uncertainty.
were collected, including p-values, HRs, standard errors, To determine the consistency of the results across studies
and 95% confidence intervals (CIs). These metrics provide and to assess the heterogeneity, two standard statistical

Volume 9 Issue 3 (2025) 124 doi: 10.36922/EJMO025120063