Role of hematological parameters in pancreatic cancer: A literature review

Table 1 The overall summary of hematological parameters in the pathogenesis of pancreatic cancer

Hematological parameters	Pathogenesis of PC
RBCs	PDAC is associated with the excessive aggregation of RBCs
RDW	Advanced tumor stages were linked to higher RDW levels. There is a correlation between RDW and the length of survival for PC patients
Platelets	Platelets have been identified as important participants in cancer, thrombosis, and hemostasis. Platelets can promote carcinogenesis and metastasis through a wide range of interplay between cancer cells and platelets. Pancreatic tumors often cause thrombosis by speeding up platelet aggregation. Platelets were once assumed to be solely involved in hemostasis, but they are now known to be important in the development of cancer and inflammation. Platelets contribute to the formation of an immunosuppressive milieu that encourages fibrotic remodeling, tumor initiation, development, metastasis, and immune evasion by releasing cytokines, growth factors, and pro-angiogenic mediators. There are several functional subtypes of neutrophils and macrophages that have both pro- and anti-tumorigenic properties
MPV	Activated platelets play a key role in tumor growth and tumor metastases. Mean platelet volume is a platelet index and is altered in patients with malignancies. There was no significant correlation seen between increased MPV and CA19-9, tumor location, or tumor size
WBCs	Patients with diabetes who had PC had greater levels of macrophage infiltration in lymph node metastases than in original tumors. The prognosis of PC was not substantially affected by type 2 diabetes or intra-tumoral leukocyte (macrophage, neutrophil, or eosinophil) infiltration alone. High macrophage or neutrophil tumor-infiltration, however, was linked to a markedly worse overall survival rate in cancer patients with type 2 diabetes
Neutrophils	Neutrophils are involved in acute inflammation. In general, neutrophils are drawn into the tumor microenvironment and have an impact on inflammation and tumor growth. Neutrophils, a vital component of the tumor microenvironment which are involved in angiogenesis, metastasis, progression, and immunosuppression in PC. Numerous biological processes that attract neutrophils to tumor lesions and stimulate carcinogenesis have been discovered. Neutrophils play an important part in the microenvironment of PC and influence tumor formation and development. Through a variety of processes, such as angiogenesis, immune suppression, immune evasion, and epithelial-mesenchymal transition, neutrophils aid in the liver metastasis of PC. The repercussions of neutrophil and macrophage activity aid in the development, hypoxia, fibrosis, and remodeling of tumors. Nuclear factor erythroid 2 is a crucial transcription factor that controls the phenotypic polarization of neutrophils. Transforming growth factor β, which is produced by metastatic tumors, activates the SMAD3 pathway in neutrophils, causing nuclear factor erythroid 2-driven polarization. By binding to the promoter of peptidylarginine deiminase 4, nuclear factor erythroid 2 stimulates its transcription, which results in the production of neutrophil extracellular traps near the invasive front. Neutrophil extracellular traps are one of them, and they are important for tumor metastasis
Lymphocytes	B lymphocytes are heavily infiltrated in pancreatic adenocarcinoma
Monocytes	It reveals two unique tumor-associated monocyte and macrophage populations that represent systemic immunological alterations in individuals with pancreatic ductal adenocarcinoma. PC-derived extracellular vesicles carry specific cargo that, upon uptake, enhance monocyte recruitment to tumor microenvironment and their subsequent differentiation to tumor-associated macrophages. High monocyte counts were a poor prognostic indicator in PC and that monocytes may directly trigger the epithelial-mesenchymal transition process in PC cells by upregulating the expression of Snail via the nuclear factor-κB signaling pathway
Eosinophils	Eosinophil accumulation and degranulation contribute to PC and fibrosis. Hypereosinophilia is a sign of malignancy in pancreatic adenocarcinoma and other solid tumor and hematological malignancies, in addition to prodromal symptoms. NOD-like receptor family pyrin domain containing 3-regulated interleukin-18, which is produced by accumulated macrophages in a murine model of PC, stimulates eosinophilic inflammation-mediated accumulation of periductal mucin and collagen, leading to the development of acinar-to-ductal metaplasia, pancreatic intraepithelial neoplasia, and intraductal papillary mucinous neoplasm
Basophils	Basophils can stimulate the formation of inflammation-driven skin tumors and are found in the immunological landscape of PC and human lung adenocarcinoma. Basophils play a useful role in the development of tumors. While basophil activation was triggered by T-cell-derived interleukin 3, basophil migration into tumor-draining lymph nodes depended in part on the production of chemokine C-C motif chemokine ligand 7/monocyte chemoattractant protein 3 by “alternatively activated” monocytes

PC: Pancreatic cancer; RBC: Red blood cell; RDW: Red cell distribution width; MPV: Mean platelet volume; WBC: White blood cell; PDAC: Pancreatic ductal adenocarcinoma; CA19-9: Carbohydrate antigen 19-9.