Proteomic biomarkers profiling in Pakistani pancreatic ductal adenocarcinoma population: a retrospective cohort study
Creators: name: Ali, Saleema Mehboob
name: Adnan, Yumna
name: Ahmad, Zubair
name: Chawla, Tabish
name: Ali, SM Adnan
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer

description: <b>Aim:</b> Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Research in various cancers suggests that investigating target biomarkers may provide directions to precision medicine. However, expression of biomarkers varies across different populations. The biomarker profile of Pakistani patients with PDAC remains unexplored. <b>Materials &amp; methods:</b> We conducted a study on 109 patients to analyze a panel of four proteins (KRAS, p53, BRCA1 and APC) using formalin-fixed paraffin-embedded tumor samples. After confirmation of diagnosis and appropriate tumor content, tissues were processed with antibody specific immunohistochemistry experiments. Subsequently, independent microscopic observation was conducted by two pathologists using scoring criteria specific for each antibody. <b>Results:</b> Statistical analysis showed that negative expression of p53 was significantly associated with positive expression of BRCA1 (<i>p</i> = 0.000) and APC (<i>p</i> = 0.007). The expression of BRCA1 was also found significantly associated with APC (<i>p</i> = 0.028). None of the protein showed association with overall survival or patient demographics. Moreover, KRAS expression was shown to be significantly associated with perineural invasion (<i>p</i> = 0.005). <b>Conclusion:</b> This is the first study that investigates protein biomarker expression in a large cohort of Pakistani PDAC patients. The findings from the study may provide directions about the population specific biomarkers and targeted therapies for these patients. Unveiling new Pancreatic ductal adenocarcinoma biomarker links: BRCA1 &amp; APC associated with p53 loss, KRAS related to perineural invasion in Pakistani cohort. Insights could transform targeted therapies! #CancerResearch #PDAC This research is the first of its kind globally to examine a combined panel of four key protein biomarkers-KRAS, p53, BRCA1 and APC-in patients with pancreatic ductal adenocarcinoma (PDAC), specifically within the Pakistani population. The study offers new insights into the potential interactions between these biomarkers and their role in PDAC progression (Heading 3.2). The analysis revealed that negative expression of p53 was significantly associated with the independent positive expressions of both BRCA1 and APC proteins. This finding highlights a possible regulatory link between these proteins, which could play a pivotal role in PDAC tumor biology, indicating the importance of these biomarkers in understanding the disease’s molecular pathways (Heading 3.3). A significant relationship was also observed between BRCA1 and APC protein expressions, suggesting that these proteins may interact within common signaling pathways. This association could provide further insights into how these markers contribute to tumor development and progression, potentially pointing to new avenues for therapeutic intervention (Heading 3.3). Among clinicopathological characteristics, KRAS expression was found to be significantly associated with perineural invasion, a condition where cancer invades surrounding nerves. Perineural invasion is known to contribute to PDAC aggressiveness and poor prognosis, making this association particularly relevant for future research aimed at improving early detection and treatment strategies (Heading 3.3). Interestingly, none of the four protein biomarkers (KRAS, p53, BRCA1 or APC) showed a statistically significant association with patient demographics or overall survival. This result suggests that while these biomarkers may play a role in tumor biology, other factors likely contribute to patient outcomes, underscoring the complexity of PDAC and the need for multifactorial approaches to improve survival rates (Heading 3.4). These findings highlight the clinical importance of the selected biomarkers, particularly in understanding the pathways driving PDAC progression. By identifying significant protein interactions, this study provides a foundation for future research into biomarker-driven therapeutic strategies. Investigating these biomarkers further could lead to the development of more targeted and effective treatments for PDAC patients, ultimately improving clinical outcomes (Heading 4). Given the significance of these initial findings, the study advocates for future larger cohort studies across multiple centers to confirm these associations. Expanding the sample size and geographical representation would enable a more comprehensive understanding of the roles of KRAS, p53, BRCA1 and APC in PDAC, helping to validate their utility as diagnostic and prognostic biomarkers (Heading 4). The study recommends further exploration of additional proteins involved in relevant signaling pathways. By investigating a broader spectrum of proteins, researchers can identify more robust pathway-based candidate biomarkers. These biomarkers could help in selecting personalized molecular therapies for PDAC, providing patients with more tailored treatment options that target specific aspects of their tumor biology. Such advancements hold the potential to improve overall patient survival and quality of life (Heading 4).