Pancreatic cancer (PC) is a highly lethal malignancy, ranking as the fourth leading cause of cancer-related deaths in Western countries [1]. Most patients die within a year of diagnosis, with a median survival of less than six months. Pancreatic ductal adenocarcinoma (PDAC) the predominant subtype, accounts for more than 200,000 deaths annually worldwide [2]. Despite advances in diagnostic technology, the asymptomatic nature of PC and the lack of specific biomarkers hinder early detection, often resulting in diagnosis at advanced stages [3]. The disease's biological behavior varies among patients, emphasizing the need for reliable markers for early detection, risk stratification, and prognosis.

MicroRNAs (miRNAs) are small non-coding RNAs that play crucial roles in gene regulation by binding to the 3′-untranslated regions of target mRNAs, thereby promoting degradation or inhibiting translation. In cancer, miRNAs may act as either oncogenes (oncomiRs) or tumor suppressors (tsmiRNAs), influencing cell growth, metastasis and survival [4].

Several studies have identified dysregulated miRNA profiles in pancreatic cancer. For example, miRNA-221 targets the tumor suppressor gene PTEN, which negatively regulates the AKT/PI3K pathway. In pancreatic cancer, upregulation of the AKT pathway promotes increased cell proliferation and metastatic potential [5]. Additionally, miRNA-199a has been implicated in the tumor stroma and cancer-associated fibroblasts (CAFs), playing a role in the progression of pancreatic tumors [6].

Inflammatory markers such as neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) have emerged as prognostic indicators in several malignancies.Elevated NLR and PLR are linked to poorer survival rates, reflecting a systemic inflammatory response. This inflammation promotes tumor growth and metastasis by weakening the body's antitumor immune defenses [7,8,9].

Research has also linked elevated NLR and PLR to lymph node involvement and recurrence risk in pancreatic cancer patients, although more studies are required to validate their predictive value. Some authors have suggested that combining NLR and PLR may enhance the accuracy of prognosis compared to using either marker alone [10]. Moreover, elevated levels of these markers may indicate the presence of locally advanced or metastatic disease, particularly in patients undergoing chemotherapy prior to surgical resection [11,12].

CA19-9 is currently the most widely used biomarker for PC, but its diagnostic value is limited due to low specificity and sensitivity. High level of CA 19-9 can be false positive, especially in cholestasis, and it may not be detectable in individuals with the Lewis-negative phenotype [13]. These limitations highlight the need for novel, more specific biomarkers for early detection.

On the other hand, miRNAs offer an attractive alternative due to their stability in biological fluids, including serum and plasma. Circulating miRNAs, encapsulated in membranous vesicles or bound to RNA-binding proteins, have been detected in patients with pancreatic cancer, making them promising candidates for non-invasive diagnostic markers [14].

This study aims to evaluate the diagnostic utility of serum miRNA 199-a and miRNA 221 in pancreatic ductal adenocarcinoma and their association with disease progression. Additionally, it seeks to investigate the correlation between the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) with tumor resectability and disease progression.