Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis

Pan, Yanfeng; Zhou, Zhigang; Wang, M; Dong, Junqiang; Du, Kun; Li, S; Liu, Y L; Lv, Pin; Gao, Jianbo

doi:10.4238/gmr15048949

Cited by 27 publications

(24 citation statements)

References 21 publications

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“…C-C motif chemokine ligand 2 (CCL2), also known as monocyte chemotactic protein-1 (MCP-1), is expressed in most human cancers [35][36][37], and plays a key role in the recruitment of macrophages and MDSCs [35,36,[38][39][40]. In general agreement with the findings that tumors accumulate macrophages and MDSCs that have pro-tumorigenic properties and express CCL2 and that CCL2 expression in tumor tissue is associated with advanced tumor stage and worse prognosis, there are several studies that report elevated levels of CCL2 in the serum of cancer patients and/or an association between elevated serum CCL2 and poor prognosis [41][42][43][44][45][46][47][48][49][50][51]. Other studies, however, found either no association between the serum CCL2 levels of cancer patients and clinical variables or that lower serum CCL2 levels were associated with poor prognosis or that higher serum CCL2 levels were associated with favorable prognosis [52][53][54][55][56][57][58][59][60].…”

Section: Introductionsupporting

confidence: 62%

“…Several studies have reported that increased expression of CCL2 in tumor tissue is associated with advanced tumor stage and worse prognosis: These studies include patients with breast cancer [65][66][67][68], prostate cancer [69,70], gastric cancer [71], colorectal cancer [72,73], esophageal squamous cell carcinoma [74], head and neck squamous cell carcinoma [75], and glial tumors [47]. In agreement with these findings, a number of studies report elevated levels of CCL2 in the serum of cancer patients and/or an association between elevated serum CCL2 and poor prognosis: Moogooei et al [47] and Pan et al [48] report elevated levels of serum CCL2 in patients with glial tumors and lung cancer. Lu et al [45] and Sharma et al [49] report an association between elevated serum CCL2 levels and poor prognosis in patients with prostate cancer, and Lu et al [44] report an association between elevated serum CCL2 levels and poor prognosis in patients with nasopharyngeal cancer.…”

Section: Discussionmentioning

confidence: 76%

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Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients

Kishimoto

Fujimoto

Ebara

et al. 2019

Preprint

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Background: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients. Methods: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA. Results: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM patients. Conclusions: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.

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Section: Introductionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 76%

Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients

Kishimoto

Fujimoto

Ebara

et al. 2019

Preprint

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“…Increasingly, lncRNAs and miRNAs have been found to act as diagnostic markers in lung cancer ( 58 – 62 ). The combination of multiple diagnostic biomarkers would greatly improve the sensitivity and specificity of lung cancer diagnosis ( 56 , 63 , 64 ). Thus, each finding is likely to contribute to the future clinical diagnosis of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

A meta‑analysis and bioinformatics exploration of the diagnostic value and molecular mechanism of miR‑193a‑5p in lung cancer

et al. 2018

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Lung cancer is a leading cause of mortality worldwide and despite recent improvements in lung cancer treatments patient mortality remains high. miR-193a-5p serves a crucial role in the initiation and development of cancer; it is necessary to understand the underlying molecular mechanisms of miR-193a-5p in lung cancer, which may enable the development of improved clinical diagnoses and therapies. The present study investigated the diagnostic value of peripheral blood and tissue miR-193a-5p expression using a microarray meta-analysis. Peripheral blood miR-193a-5p was revealed to be upregulated in patients with lung cancer. The pooled area under the curve (AUC) was 0.67, with a sensitivity and specificity of 0.74 and 0.56, respectively. Conversely, the peripheral tissue miR-193a-5p expression in patients with lung cancer was significantly downregulated. The pooled AUC was 0.83, and the sensitivity and specificity were 0.65 and 0.89, respectively. Through bioinformatics analysis, three Kyoto Encyclopedia of Genes and Genomes (KEGG) terms, pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway, were identified as associated with miR-193a-5p in lung cancer. In addition, in lung cancer, six key miR-193a-5p target genes, receptor tyrosine-protein kinase erbB-2 (ERBB2), nuclear cap-binding protein subunit 2 (NCBP2), collagen α-1(I) chain (COL1A1), roprotein convertase subtilisin/kexin type 9 (PCSK9), casein kinase II subunit α (CSNK2A1) and nucleolar transcription factor 1 (UBTF), were identified, five of which were significantly upregulated (ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF). The protein expression of ERBB2, NCBP2, COL1A1, CSNK2A1 and UBTF was also upregulated. NCBP2 and CSNK2A1 were negatively correlated with miR-193a-5p. The results demonstrated that miR-193a-5p exhibited opposite expression patterns in peripheral blood and tissue. Upregulated peripheral blood miR-193a-5p and downregulated tissue miR-193a-5p may be promising diagnostic biomarkers in lung cancer. In addition, the KEGG terms pathways in cancer, prostate cancer and RIG-I-like receptor signaling pathway may suggest which pathways serve vital roles in lung cancer by regulating miR-193a-5p. In addition, six genes, ERBB2, COL1A1, PCSK9, UBTF and particularly NCBP2 and CSNK2A1, may be key target genes of miR-193a-5p in lung cancer.

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“…CCL2 binds to its receptor CCR2 to mediate its effect through an autocrine or paracrine manner (130). Expression of CCL2, CCR2 or in combination with IL6 and IL10 correlates with a worse prognosis in lung cancer patients (61,78,79). In various cancers, the crosstalk of TAMs with tumor cells via the CCL2/CCR2 axis play multiple roles in cancer development, such as monocyte/macrophage recruitment at the tumor site (131), tumor progression, EMT, invasion, and metastasis (132).…”

Section: Chemokines Ccl2mentioning

confidence: 99%

Macrophage and Tumor Cell Cross-Talk Is Fundamental for Lung Tumor Progression: We Need to Talk

et al. 2020

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Regardless of the promising results of certain immune checkpoint blockers, current immunotherapeutics have met a bottleneck concerning response rate, toxicity, and resistance in lung cancer patients. Accumulating evidence forecasts that the crosstalk between tumor and immune cells takes center stage in cancer development by modulating tumor malignancy, immune cell infiltration, and immune evasion in the tumor microenvironment (TME). Cytokines and chemokines secreted by this crosstalk play a major role in cancer development, progression, and therapeutic management. An increased infiltration of Tumor-associated macrophages (TAMs) was observed in most of the human cancers, including lung cancer. In this review, we emphasize the role of cytokines and chemokines in TAM-tumor cell crosstalk in the lung TME. Given the role of cytokines and chemokines in immunomodulation, we propose that TAM-derived cytokines and chemokines govern the cancer-promoting immune responses in the TME and offer a new immunotherapeutic option for lung cancer treatment.

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Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis

Cited by 27 publications

References 21 publications

Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients

Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients

A meta‑analysis and bioinformatics exploration of the diagnostic value and molecular mechanism of miR‑193a‑5p in lung cancer

Macrophage and Tumor Cell Cross-Talk Is Fundamental for Lung Tumor Progression: We Need to Talk

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