Research progress on the expression heterogeneity of ficolin 3 in lung cancer and its relationship with the immune microenvironment_West China Medical Journal

Authors：

LI Shipeng ¹ , LI Jie ^1,2 ,  ZHANG Yu ^1,2

1. Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;
2. Department of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P. R. China;

Corresponding?author：

ZHANG Yu, Email: 543703371@qq.com

Keywords：

Non-small cell lung carcinoma; ficolin 3; expression heterogeneity; immune microenvironment

DOI：

10.7507/1002-0179.202605042

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Ficolin (FCN) 3 is a soluble pattern recognition molecule in the lectin complement pathway, primarily expressed in the liver and lung. Existing studies indicate that FCN3 is generally downregulated in lung adenocarcinoma and squamous cell carcinoma tissues, though its prognostic significance depends on histological subtypes and analytical levels. This review summarizes the expression heterogeneity of FCN3 in lung cancer and its relationship with the immune microenvironment. At present, FCN3 can be considered a candidate stratification marker linking the lectin complement pathway, tissue composition, and immune microenvironment, but its cellular origin, measurement level, and incremental clinical value require further clarification.

Citation： LI Shipeng, LI Jie, ZHANG Yu. Research progress on the expression heterogeneity of ficolin 3 in lung cancer and its relationship with the immune microenvironment. West China Medical Journal, 2026, 41(9): 1545-1548. doi: 10.7507/1002-0179.202605042 Copy

1.	Sung H, Filho AM, Laversanne M, et al. Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries[J]. CA Cancer J Clin, 2026, 76(4): e70090.
2.	Fox AH, Osarogiagbon RU, Farjah F, et al. The American Cancer Society national lung cancer roundtable strategic plan: advancing comprehensive biomarker testing in non-small cell lung cancer[J]. Cancer, 2024, 130(24): 4188-4199.
3.	Duchemann B, Remon J, Naigeon M, et al. Current and future biomarkers for outcomes with immunotherapy in non-small cell lung cancer[J]. Transl Lung Cancer Res, 2021, 10(6): 2937-2954.
4.	Holder AM, Dedeilia A, Sierra-Davidson K, et al. Defining clinically useful biomarkers of immune checkpoint inhibitors in solid tumours[J]. Nat Rev Cancer, 2024, 24(7): 498-512.
5.	Cedzyński M, ?wierzko AS. Components of the lectin pathway of complement in solid tumour cancers[J]. Cancers (Basel), 2022, 14(6): 1543.
6.	Mastellos DC, Hajishengallis G, Lambris JD. A guide to complement biology, pathology and therapeutic opportunity[J]. Nat Rev Immunol, 2024, 24(2): 118-141.
7.	Matsushita M, Kuraya M, Hamasaki N, et al. Activation of the lectin complement pathway by H-ficolin (Hakata antigen)[J]. J Immunol, 2002, 168(7): 3502-3506.
8.	Garred P, Genster N, Pilely K, et al. A journey through the lectin pathway of complement-MBL and beyond[J]. Immunol Rev, 2016, 274(1): 74-97.
9.	Zacho RM, Jensen L, Terp R, et al. Studies of the pattern recognition molecule H-ficolin: specificity and purification[J]. J Biol Chem, 2012, 287(11): 8071-8081.
10.	Hummelshoj T, Fog LM, Madsen HO, et al. Comparative study of the human ficolins reveals unique features of ficolin-3 (Hakata antigen)[J]. Mol Immunol, 2008, 45(6): 1623-1632.
11.	Akaiwa M, Yae Y, Sugimoto R, et al. Hakata antigen, a new member of the ficolin/opsonin p35 family, is a novel human lectin secreted into bronchus/alveolus and bile[J]. J Histochem Cytochem, 1999, 47(6): 777-786.
12.	Ma D, Liu P, Wen J, et al. FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway[J]. Int J Biol Sci, 2023, 19(2): 362-376.
13.	Jiawei Z, Min M, Yingru X, et al. Identification of key genes in lung adenocarcinoma and establishment of prognostic mode[J]. Front Mol Biosci, 2020, 7: 561456.
14.	Zhao M, Tan X, Wu X. The role of ficolins in lung injury[J]. J Innate Immun, 2024, 16(1): 440-450.
15.	Plovsing RR, Berg RM, Munthe-Fog L, et al. Alveolar recruitment of ficolin-3 in response to acute pulmonary inflammation in humans[J]. Immunobiology, 2016, 221(5): 690-697.
16.	Bidula S, Sexton DW, Yates M, et al. H-ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses[J]. Immunology, 2015, 146(2): 281-291.
17.	Jang H, Jun Y, Kim S, et al. FCN3 functions as a tumor suppressor of lung adenocarcinoma through induction of endoplasmic reticulum stress[J]. Cell Death Dis, 2021, 12(4): 407.
18.	Zhang Z, Geng X, Yin M, et al. Unveiling ficolins: diagnostic and prognostic biomarkers linked to the tumor microenvironment in lung cancer[J]. World J Surg Oncol, 2024, 22(1): 273.
19.	李偉, 祖玲玲, 徐嵩. FCN3 可作為肺鱗癌預后及免疫治療的潛在生物標志物[J]. 中國肺癌雜志, 2025, 28(2): 114-130.
20.	Uhlén M, Fagerberg L, Hallstr?m BM, et al. Tissue-based map of the human proteome[J]. Science, 2015, 347(6220): 1260419.
21.	Thul PJ, Lindskog C. The human protein atlas: a spatial map of the human proteome[J]. Protein Sci, 2018, 27(1): 233-244.
22.	Lindskog C, Fagerberg L, Hallstr?m B, et al. The lung-specific proteome defined by integration of transcriptomics and antibody-based profiling[J]. FASEB J, 2014, 28(12): 5184-5196.
23.	Markiewski MM, DeAngelis RA, Benencia F, et al. Modulation of the antitumor immune response by complement[J]. Nat Immunol, 2008, 9(11): 1225-1235.
24.	Senent Y, Tavira B, Pio R, et al. The complement system as a regulator of tumor-promoting activities mediated by myeloid-derived suppressor cells[J]. Cancer Lett, 2022, 549: 215900.
25.	Jiang P, Gu S, Pan D, et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response[J]. Nat Med, 2018, 24(10): 1550-1558.
26.	Charoentong P, Finotello F, Angelova M, et al. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade[J]. Cell Rep, 2017, 18(1): 248-262.
27.	Samstein RM, Lee CH, Shoushtari AN, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types[J]. Nat Genet, 2019, 51(2): 202-206.
28.	Lambrechts D, Wauters E, Boeckx B, et al. Phenotype molding of stromal cells in the lung tumor microenvironment[J]. Nat Med, 2018, 24(8): 1277-1289.
29.	Guo X, Zhang Y, Zheng L, et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing[J]. Nat Med, 2018, 24(7): 978-985.
30.	Zilionis R, Engblom C, Pfirschke C, et al. Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species[J]. Immunity, 2019, 50(5): 1317-1334.
31.	Wu F, Fan J, He Y, et al. Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer[J]. Nat Commun, 2021, 12(1): 2540.
32.	Maynard A, McCoach CE, Rotow JK, et al. Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing[J]. Cell, 2020, 182(5): 1232-1251.
33.	De Zuani M, Xue H, Park JS, et al. Single-cell and spatial transcriptomics analysis of non-small cell lung cancer[J]. Nat Commun, 2024, 15(1): 4388.
34.	Hofman P, Christopoulos P, D’Haene N, et al. Proposal of real-world solutions for the implementation of predictive biomarker testing in patients with operable non-small cell lung cancer[J]. Lung Cancer, 2025, 201: 108107.
35.	Penault-Llorca F, Socinski MA. Emerging molecular testing paradigms in non-small cell lung cancer management-current perspectives and recommendations[J]. Oncologist, 2025, 30(3): oyae357.
36.	蘇政軍, 黃珊珊, 陳萬進. 血清纖維膠凝蛋白 3、膠原三股螺旋重復蛋白 1 對非小細胞肺癌的診斷價值及與臨床病理特征的關系[J]. 臨床外科雜志, 2024, 32(2): 164-167.
37.	Kalkanis A, Papadopoulos D, Testelmans D, et al. Bronchoalveolar lavage fluid-isolated biomarkers for the diagnostic and prognostic assessment of lung cancer[J]. Diagnostics (Basel), 2022, 12(12): 2949.
38.	Rolfo C, Mack P, Scagliotti GV, et al. Liquid biopsy for advanced NSCLC: a consensus statement from the international association for the study of lung cancer[J]. J Thorac Oncol, 2021, 16(10): 1647-1662.

1. Sung H, Filho AM, Laversanne M, et al. Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries[J]. CA Cancer J Clin, 2026, 76(4): e70090.
2. Fox AH, Osarogiagbon RU, Farjah F, et al. The American Cancer Society national lung cancer roundtable strategic plan: advancing comprehensive biomarker testing in non-small cell lung cancer[J]. Cancer, 2024, 130(24): 4188-4199.
3. Duchemann B, Remon J, Naigeon M, et al. Current and future biomarkers for outcomes with immunotherapy in non-small cell lung cancer[J]. Transl Lung Cancer Res, 2021, 10(6): 2937-2954.
4. Holder AM, Dedeilia A, Sierra-Davidson K, et al. Defining clinically useful biomarkers of immune checkpoint inhibitors in solid tumours[J]. Nat Rev Cancer, 2024, 24(7): 498-512.
5. Cedzyński M, ?wierzko AS. Components of the lectin pathway of complement in solid tumour cancers[J]. Cancers (Basel), 2022, 14(6): 1543.
6. Mastellos DC, Hajishengallis G, Lambris JD. A guide to complement biology, pathology and therapeutic opportunity[J]. Nat Rev Immunol, 2024, 24(2): 118-141.
7. Matsushita M, Kuraya M, Hamasaki N, et al. Activation of the lectin complement pathway by H-ficolin (Hakata antigen)[J]. J Immunol, 2002, 168(7): 3502-3506.
8. Garred P, Genster N, Pilely K, et al. A journey through the lectin pathway of complement-MBL and beyond[J]. Immunol Rev, 2016, 274(1): 74-97.
9. Zacho RM, Jensen L, Terp R, et al. Studies of the pattern recognition molecule H-ficolin: specificity and purification[J]. J Biol Chem, 2012, 287(11): 8071-8081.
10. Hummelshoj T, Fog LM, Madsen HO, et al. Comparative study of the human ficolins reveals unique features of ficolin-3 (Hakata antigen)[J]. Mol Immunol, 2008, 45(6): 1623-1632.
11. Akaiwa M, Yae Y, Sugimoto R, et al. Hakata antigen, a new member of the ficolin/opsonin p35 family, is a novel human lectin secreted into bronchus/alveolus and bile[J]. J Histochem Cytochem, 1999, 47(6): 777-786.
12. Ma D, Liu P, Wen J, et al. FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway[J]. Int J Biol Sci, 2023, 19(2): 362-376.
13. Jiawei Z, Min M, Yingru X, et al. Identification of key genes in lung adenocarcinoma and establishment of prognostic mode[J]. Front Mol Biosci, 2020, 7: 561456.
14. Zhao M, Tan X, Wu X. The role of ficolins in lung injury[J]. J Innate Immun, 2024, 16(1): 440-450.
15. Plovsing RR, Berg RM, Munthe-Fog L, et al. Alveolar recruitment of ficolin-3 in response to acute pulmonary inflammation in humans[J]. Immunobiology, 2016, 221(5): 690-697.
16. Bidula S, Sexton DW, Yates M, et al. H-ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses[J]. Immunology, 2015, 146(2): 281-291.
17. Jang H, Jun Y, Kim S, et al. FCN3 functions as a tumor suppressor of lung adenocarcinoma through induction of endoplasmic reticulum stress[J]. Cell Death Dis, 2021, 12(4): 407.
18. Zhang Z, Geng X, Yin M, et al. Unveiling ficolins: diagnostic and prognostic biomarkers linked to the tumor microenvironment in lung cancer[J]. World J Surg Oncol, 2024, 22(1): 273.
19. 李偉, 祖玲玲, 徐嵩. FCN3 可作為肺鱗癌預后及免疫治療的潛在生物標志物[J]. 中國肺癌雜志, 2025, 28(2): 114-130.
20. Uhlén M, Fagerberg L, Hallstr?m BM, et al. Tissue-based map of the human proteome[J]. Science, 2015, 347(6220): 1260419.
21. Thul PJ, Lindskog C. The human protein atlas: a spatial map of the human proteome[J]. Protein Sci, 2018, 27(1): 233-244.
22. Lindskog C, Fagerberg L, Hallstr?m B, et al. The lung-specific proteome defined by integration of transcriptomics and antibody-based profiling[J]. FASEB J, 2014, 28(12): 5184-5196.
23. Markiewski MM, DeAngelis RA, Benencia F, et al. Modulation of the antitumor immune response by complement[J]. Nat Immunol, 2008, 9(11): 1225-1235.
24. Senent Y, Tavira B, Pio R, et al. The complement system as a regulator of tumor-promoting activities mediated by myeloid-derived suppressor cells[J]. Cancer Lett, 2022, 549: 215900.
25. Jiang P, Gu S, Pan D, et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response[J]. Nat Med, 2018, 24(10): 1550-1558.
26. Charoentong P, Finotello F, Angelova M, et al. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade[J]. Cell Rep, 2017, 18(1): 248-262.
27. Samstein RM, Lee CH, Shoushtari AN, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types[J]. Nat Genet, 2019, 51(2): 202-206.
28. Lambrechts D, Wauters E, Boeckx B, et al. Phenotype molding of stromal cells in the lung tumor microenvironment[J]. Nat Med, 2018, 24(8): 1277-1289.
29. Guo X, Zhang Y, Zheng L, et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing[J]. Nat Med, 2018, 24(7): 978-985.
30. Zilionis R, Engblom C, Pfirschke C, et al. Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species[J]. Immunity, 2019, 50(5): 1317-1334.
31. Wu F, Fan J, He Y, et al. Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer[J]. Nat Commun, 2021, 12(1): 2540.
32. Maynard A, McCoach CE, Rotow JK, et al. Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing[J]. Cell, 2020, 182(5): 1232-1251.
33. De Zuani M, Xue H, Park JS, et al. Single-cell and spatial transcriptomics analysis of non-small cell lung cancer[J]. Nat Commun, 2024, 15(1): 4388.
34. Hofman P, Christopoulos P, D’Haene N, et al. Proposal of real-world solutions for the implementation of predictive biomarker testing in patients with operable non-small cell lung cancer[J]. Lung Cancer, 2025, 201: 108107.
35. Penault-Llorca F, Socinski MA. Emerging molecular testing paradigms in non-small cell lung cancer management-current perspectives and recommendations[J]. Oncologist, 2025, 30(3): oyae357.
36. 蘇政軍, 黃珊珊, 陳萬進. 血清纖維膠凝蛋白 3、膠原三股螺旋重復蛋白 1 對非小細胞肺癌的診斷價值及與臨床病理特征的關系[J]. 臨床外科雜志, 2024, 32(2): 164-167.
37. Kalkanis A, Papadopoulos D, Testelmans D, et al. Bronchoalveolar lavage fluid-isolated biomarkers for the diagnostic and prognostic assessment of lung cancer[J]. Diagnostics (Basel), 2022, 12(12): 2949.
38. Rolfo C, Mack P, Scagliotti GV, et al. Liquid biopsy for advanced NSCLC: a consensus statement from the international association for the study of lung cancer[J]. J Thorac Oncol, 2021, 16(10): 1647-1662.

West China Medical Journal

Research progress on the expression heterogeneity of ficolin 3 in lung cancer and its relationship with the immune microenvironment

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content