Autophagy-related protein LC3β and its association with clinical-pathological characteristics, mismatch repair proteins and survival in colorectal carcinoma
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Date
2025
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frontiers
Abstract
Introduction: Autophagy is a metabolic process that serves to maintain cellular
homeostasis as well as enable the cell to adapt to metabolic stress. In malignant
cells, autophagy has been associated with drug resistance, metastasis and
poor outcome. Colorectal carcinoma is a leading cause of cancer morbidity
and mortality worldwide. The management and outcome are dependent on
the tumor clinical and pathological characteristics. Autophagy is a potential
therapeutic target as well as prognostic biomarker given its role in cancer
pathogenesis. This study aimed at evaluating the autophagy status of colorectal
carcinomas for tumors diagnosed at the Aga Khan University Hospital, Nairobi
and establish its association with clinical-pathological characteristics including
age, tumor location, tumor grade, tumor pathological stage, tumor nodal stage,
tumor budding, tumor-infiltrating lymphocytes (TILs), Mismatch repair protein
status (MMR), HER2 status and patient survival.
Methods: The study assessed the autophagy status of 114 colorectal carcinoma
cases using immunohistochemistry for autophagy related protein LC3β. The
clinical-pathological characteristics were determined by examining the medical
records and evaluation of hematoxylin and eosin-stained slides. HER2 and MMR
status were evaluated using immunohistochemistry. The treatment outcome was
determined from the patient’s records by checking for date of last visit or death.
Results and discussion: The mean age of patients in our study was 58years.
There were more males 61.8% (n = 70) than females 38.6% (n = 44). Most
of the patients had high pathological tumor stage of pT3 and pT4. Majority of
the tumors showed intermediate tumor budding and weak tumor-infiltrating
lymphocytes. The mismatch repair deficiency and HER2 overexpression were
found in 14.9% (n = 17) and 2.6% (n = 3) of the cases respectively. LC3β was
overexpressed in 36% (n = 41) of the cases and was significantly more common in
females (p = 0.013). The LC3β status showed no significant association with age,
tumor location, tumor grade, tumor stage, nodal stage, tumor budding, tumorinfiltrating lymphocytes, MMR status, HER2 status or patient survival. Future
prospective studies are recommended to further explore the utility of autophagy
as a prognostic and predictive biomarker
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Gakinya S, Nzioka AK, Mugo AG, Onyuma T and Ogutu J (2025) Autophagy-related protein LC3β and its association with clinical-pathological characteristics, mismatch repair proteins and survival in colorectal carcinoma. Front. Med. 12:1512127. doi: 10.3389/fmed.2025.1512127