Abstract
Hepatocellular carcinoma (HCC) remains a significant health problem with a substantial genetic predisposition. The liver harbors the largest proportion of macrophages among all the solid organs. There is considerable controversy regarding the relationship between the macrophage receptor with collagenous structure (MARCO) and tumor development and progression. Accordingly, we performed this case–control study to determine whether associations exist between the MARCO single nucleotide polymorphism rs6761637 and HCC susceptibility and clinical characteristics. We successfully genotyped 586 HCC cases and 647 controls using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The overall genotype distribution of rs6761637 was similar in the HCC and control groups (P = 0.143). However, the CT + CC genotypes of rs6761637 were slightly more common in the HCC group among female (P = 0.021), overweight (body mass index ≥ 24 kg/m2, P = 0.003), and nonsmoking (P = 0.022) individuals. The minor C allele carriers had a 1.47-fold increased risk of developing large tumor nodules (P = 0.041). rs6761637 did not affect the recurrence-free or overall survival rate of patients with HCC (P = 0.247 and 0.304, respectively). In conclusion, this is the first report of the association between MARCO genetic variations and HCC risk. These results suggest that the MARCO rs6761637 polymorphism may play a regulatory role in HCC carcinogenesis, but it does not seem to predict prognosis.
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We would like to thank Editage (www.editage.com) for their assistance with English language editing.
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This work was funded with grants from the National Natural Science Foundation of China (grant numbers: 81602910 and 81702002), the Department of Science and Technology of Sichuan Province (grant numbers: 2020YFS0137 and 2019YFS0284), and the Sichuan Provincial Cadre Health Research Project of the Sichuan Provincial Health Commission (grant number: 2020–117).
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Bei Cai and Fei Liu designed the study; Zhenzhen Su, Limei Luo, and Fei Liu collected the samples, performed the experiments, and conducted the data management; Zhenzhen Su, Xiaojuan Wu, Bin Wei, and Lu Wang performed the statistical analysis; Zhenzhen Su, Limei Luo, and Bei Cai interpreted the results and wrote the original draft; all authors reviewed the manuscript.
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This study complied with the Declaration of Helsinki. We performed the study with prior written informed consent from the patients and the approval of the ethics committee of Sichuan University (2017–264).
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12026_2022_9271_MOESM1_ESM.tif
Supplementary Fig. 1 Liver MARCO expression levels in healthy subjects according to the GTEx database. GTEx, Genotype-Tissue Expression; TPM, transcripts per million. The median TPM of MARCO in males (n =161) and females (n =65) was 4.223 and 9.588, respectively. Mann-Whitney U test was used for comparison. (TIF 631 KB)
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Su, Z., Luo, L., Wu, X. et al. Association of the MARCO polymorphism rs6761637 with hepatocellular carcinoma susceptibility and clinical characteristics. Immunol Res 70, 400–407 (2022). https://doi.org/10.1007/s12026-022-09271-2
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DOI: https://doi.org/10.1007/s12026-022-09271-2