Role of tumor markers and cytokines in the pathogenesis of lung cancer

Table 1 The circulating levels of tumor markers and cytokines in the pathogenesis of lung cancer

Tumor markers and cytokines	Circulating levels
CEA	Increased level
SCC	Not yet reported
CK19	Increased level
TNF-α	Increased level
GM-CSF	Increased level
IFN-γ	Increased level
IL-1	Increased level
IL-2	Increased level
IL-4	Increased level
IL-6	Increased level
IL-8	Increased level
IL-10	Increased level
MCP-1	Increased level
NSE	Increased level

CEA: Carcinoembryonic antigen; SCC: Squamous cell carcinoma; TNF-α: Tumor necrosis factor-α; GM-CSF: Granulocyte-macrophage colony-stimulating factor; IFN-γ: Interferon-γ; IL: Interleukin; MCP-1: Monocyte chemoattractant protein-1; NSE: Neuron-specific enolase.

Table 2 The overall summary of tumor markers and cytokines pathogenesis in lung cancer

Tumor markers and cytokines	Pathogenesis in lung cancer
TNF-α	In lung cancer, TNF-α contributes to tumor initiation, progression, and metastasis
	TNF is a major factor in non-small cell lung cancer caused by inflammation, angiogenesis, and metastasis
IFN-γ	Modulates the TME and is negatively correlated with the expression of immune metagenes
	Causing apoptosis in the lung cancer cells and restoring RNase L function
	IFN-γ-enhanced CD47 expression is a unique mechanism that promotes the development of human lung adenocarcinoma
IL-1	IL-1β binds to this receptor and initiates signaling pathways, such as the MAPK, cyclooxygenase, and NF-κB pathways, which result in the activation of macrophages, the intratumoral accumulation of immunosuppressive myeloid cells, and the growth, invasiveness, metastasis, and angiogenesis of tumors
	Tumor-cell motility and invasion are promoted by promoting glycolysis of LUAD cells through p38 signaling
IL-2	IL-2 expression was substantially positively connected with several immune cells, such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells
IL-4	The Th2 cytokine IL-4 increased macrophage-dependent tumor cell extravasation
IL-6	IL-6/STAT3 signaling stimulated the growth of lung cancer cells by inducing the cell proliferation regulator cyclin D1
	The development of depression and lung cancer may be related to the up-regulation of indoleamine 2,3-dioxygenase brought on by IL-6
	Tumorigenesis and metastasis
IL-8	Tumor-promoting characteristics
	Increased cell proliferation
	CXCR1 receptor primarily mediates the mitogenic action of IL-8 in lung cancer, and it can operate as an autocrine and/or paracrine growth factor for lung cancer cells
	Angiogenesis and lung cancer spread
	IL-8 causes non-small cell lung cancer cells to proliferate by transactivating the epidermal growth factor receptor
	IL-8 increases epithelial cell proliferation
IL-10	A multifunctional cytokine with immunosuppressive and anti-angiogenic qualities, IL-10 is crucial to the pathophysiology of cancer
	The regulation of tumor development and metastasis may be significantly influenced by IL-10
	Development of lung cancer
	Both IL-10 and IL-10R were shown to be elevated in the cells surrounding the lung tumor cells, and IL-10R was mostly expressed on the surface of Foxp-3+ T-regulatory lymphocytes infiltrating the patients' tumors, where its expression was negatively linked with programmed cell death 1
IL-6 and TNF-α	IL-6 and TNF-α levels were positively correlated with distant metastasis and lymph node metastasis
	They were negatively correlated with E-cadherin levels and positively correlated with N-cadherin and vimentin levels
	To sum up, IL-6 and TNF-α can cause the epithelial-mesenchymal transition, which in turn can encourage lung cancer spread

TNF: Tumor necrosis factor; TME: Tumor microenvironment; IFN-γ: Interferon-γ; IL: Interleukin; LUAD: Lung adenocarcinoma.