Expression of chemerin and B7 family proteins in lung adenocarcinoma — pilot study
Abstract
Introduction: Lung cancer is the most commonly diagnosed cancer with 2.2 million cases in 2020 and
causes 1.8 million deaths. Early lung cancer often has no symptoms and can only be detected by medical
imaging. When symptoms do appear, they are often respiratory problems —coughing, breathlessness
or chest pain — and systemic problems — loss of appetite, weight loss, general weakness, fever and
night sweats. There are two main types of lung cancer: small cell lung cancer (SCLC; 15% of cases) and
non-small cell lung cancer (NSCLC; 85% of cases).
Material and methods: This study included evaluation of CMKLR1, PD-1, B7H3, B7H4 and HHLA2 expression,
along with CD8 + T-cell population, TILs and budding in H + E stained slides using IHC. Although there was no
clear association between the analysed expressions and the T parameter, this study, which included 22 archived
lung adenocarcinoma cases from patients undergoing radical lobectomy, revealed significant negative correlations
between HHLA2 expression and tumour grade, as well as between CMKLR1 expression and tumour grade.
Results: Furthermore, CMKLR1 expression among lymphocytes showed a positive correlation with TILs.
Keywords: NSCLCimmunohistochemical expressionB7H3TILsCMKLR1
References
- Pascoe HM, Knipe HC, Pascoe D, et al. The many faces of lung adenocarcinoma: a pictorial essay. J Med Imaging Radiat Oncol. 2018; 62(5): 654–661.
- Schiller JH, Gazdar AF. Lung cancer in never smokers--a different disease. Nat Rev Cancer. 2007; 7(10): 778–790.
- Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab. 2000; 11(8): 327–332.
- Umar MI, Hassan W, Murtaza G, et al. The adipokine component in the molecular regulation of cancer cell survival, proliferation and metastasis. Pathol Oncol Res. 2021; 27: 1609828.
- Yoshimura T, Oppenheim JJ. Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); two multifunctional receptors with unusual properties. Exp Cell Res. 2011; 317(5): 674–684.
- Nakamura N, Naruse K, Kobayashi Y, et al. Chemerin promotes angiogenesis in vivo. Physiol Rep. 2018; 6(24): e13962.
- Kiczmer P, Mielcarska S, Chrabańska M, et al. The concentration of CMKLR1 expression on clinicopathological parameters of colorectal cancer: A preliminary study. Medicina (Kaunas). 2021; 57(12).
- Kula A, Dawidowicz M, Kiczmer P, et al. The role of genetic polymorphism within PD-L1 gene in cancer. Review. Exp Mol Pathol. 2020; 116: 104494.
- Li M, Che N, Feng Y, et al. B7-H4 expression promotes non-small cell lung cancer progression via AMPK/mTOR signaling. Exp Mol Pathol. 2022; 125: 104755.
- Meder W, Wendland M, Busmann A, et al. Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23. FEBS Lett. 2003; 555(3): 495–499.
- Kumar JD, Aolymat I, Tiszlavicz L, et al. Chemerin acts via CMKLR1 and GPR1 to stimulate migration and invasion of gastric cancer cells: putative role of decreased TIMP-1 and TIMP-2. Oncotarget. 2019; 10(2): 98–112.
- Pachynski RK, Zabel BA, Kohrt HE, et al. The chemoattractant chemerin suppresses melanoma by recruiting natural killer cell antitumor defenses. J Exp Med. 2012; 209(8): 1427–1435.
- Su X, Cheng Ye, Zhang G, et al. Chemerin in inflammatory diseases. Clin Chim Acta. 2021; 517: 41–47.
- Bolandi N, Derakhshani A, Hemmat N, et al. The positive and negative immunoregulatory role of B7 family: promising novel targets in gastric cancer treatment. Int J Mol Sci. 2021; 22(19).
- Altan M, Toki MI, Gettinger SN, et al. Differential expression and significance of PD-L1, IDO-1, and B7-H4 in human lung cancer. Clin Cancer Res. 2017; 23(2): 370–378.
- Inamura K, Yokouchi Y, Kobayashi M, et al. WITHDRAWN: Tumor B7-H3 (CD276) expression and smoking history in relation to lung adenocarcinoma prognosis. Lung Cancer. 2016; 243: 21–28.
- Chen Y, Hu R, Li X, et al. B7-H4 and HHLA2, members of B7 family, are aberrantly expressed in EGFR mutated lung adenocarcinoma. Pathol Res Pract. 2020; 216(10): 153134.
- Sun W, Li S, Tang G, et al. HHLA2 deficiency inhibits non-small cell lung cancer progression and THP-1 macrophage M2 polarization. Cancer Med. 2021; 10(15): 5256–5269.