Research progress of biomarkers for non-small cell lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

HONG Ziqiang ^1,2 , JIN Dacheng ² , BAI Xiangdou ^1,2 , CUI Baiqiang ^1,2 ,  GOU Yunjiu ²

1. The First Clinical Department of Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, P. R. China;
2. Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, 730000, P. R. China;

Corresponding author：

GOU Yunjiu, Email: gouyunjiu@163.com

Keywords：

Biomarker; non-small cell lung cancer; targeted therapy; immunotherapy; diagnosis; prognosis; review

DOI：

10.7507/1007-4848.202204084

Video：

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Abstract Full text Figures/Tables Video References Cited by

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite growing efforts for its early detection by screening populations at risk, the majority of lung cancer patients are still diagnosed in an advanced stage. In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been improved significantly. Emerging options of targeted therapies and immunotherapies have shifted the management of lung cancer to a more personalized treatment approach, significantly influencing the clinical course and outcome of the disease. At present, molecular biomarkers are becoming a powerful tool for diagnosing cancer, predicting treatment response outcomes, and assessing prognosis. In this review, we summarized the biomarkers relevant to the diagnosis, prediction, and prognosis of NSCLC as well as promising novel predictive biomarkers in the future.

Citation： HONG Ziqiang, JIN Dacheng, BAI Xiangdou, CUI Baiqiang, GOU Yunjiu. Research progress of biomarkers for non-small cell lung cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2024, 31(2): 311-318. doi: 10.7507/1007-4848.202204084 Copy

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37.	Jänne PA, van den Heuvel MM, Barlesi F, et al. Selumetinib plus docetaxel compared with docetaxel alone and progression-free survival in patients with KRAS-mutant advanced non-small cell lung cancer: The SELECT-1 randomized clinical trial. JAMA, 2017, 317(18): 1844-1853.
38.	Nikolinakos PG, Altorki N, Yankelevitz D, et al. Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. Cancer Res, 2010, 70(6): 2171-2179.
39.	Kim HR, Kang HN, Shim HS, et al. Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma. Ann Oncol, 2017, 28(6): 1250-1259.
40.	Ahmadzada T, Kao S, Reid G, et al. An update on predictive biomarkers for treatment selection in non-small cell lung cancer. J Clin Med, 2018, 7(6): 153.
41.	Yang H, Liang SQ, Schmid RA, et al. New horizons in KRAS-mutant lung cancer: Dawn after darkness. Front Oncol, 2019, 9: 953.
42.	Helsten T, Elkin S, Arthur E, et al. The FGFR landscape in cancer: Analysis of 4, 853 tumors by next-generation sequencing. Clin Cancer Res, 2016, 22(1): 259-267.
43.	Thomson S, Petti F, Sujka-Kwok I, et al. Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy. Clin Exp Metastasis, 2008, 25(8): 843-854.
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54.	黄川, 杨雪. 非小细胞肺癌免疫治疗生物标志物的研究进展. 中国肺癌杂志, 2021, 24(11): 777-783.
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1. Zheng RS, Zhang SW, He J, et al. Cancer incidence and mortality in China, 2016. JNCC, 2022, 2(1): 1-9.
2. Travis WD, Brambilla E, Burke AP, et al. Introduction to the 2015 World Health Organization classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol, 2015, 10(9): 1240-1242.
3. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin, 2022, 72(1): 7-33.
4. Zeng H, Chen W, Zheng R, et al. Changing cancer survival in China during 2003-15: A pooled analysis of 17 population-based cancer registries. Lancet Glob Health, 2018, 6(5): e555-e567.
5. 赫捷, 李霓, 陈万青, 等. 中国肺癌筛查与早诊早治指南(2021, 北京). 中国肿瘤, 2021, 30(2): 81-111.
6. Davies JC, Wainwright CE, Canny GJ, et al. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med, 2013, 187(11): 1219-1225.
7. Sears CR, Mazzone PJ. Biomarkers in lung cancer. Clin Chest Med, 2020, 41(1): 115-127.
8. Sandfeld-Paulsen B, Jakobsen KR, Bæk R, et al. Exosomal proteins as diagnostic biomarkers in lung cancer. J Thorac Oncol, 2016, 11(10): 1701-1710.
9. Alipoor SD, Mortaz E, Varahram M, et al. The potential biomarkers and immunological effects of tumor-derived exosomes in lung cancer. Front Immunol, 2018, 9: 819.
10. Mo F, Xu Y, Zhang J, et al. Effects of hypoxia and radiation-induced exosomes on migration of lung cancer cells and angiogenesis of umbilical vein endothelial cells. Radiat Res, 2020, 194(1): 71-80.
11. Chen F, Wang X, Han X, et al. Diagnostic value of Cyfra21-1, SCC and CEA for differentiation of early-stage NSCLC from benign lung disease. Int J Clin Exp Med, 2015, 8(7): 11295-300.
12. Fang R, Zhu Y, Khadka VS, et al. The evaluation of serum biomarkers for non-small cell lung cancer (NSCLC) diagnosis. Front Physiol, 2018, 9: 1710.
13. Jiang ZF, Wang M, Xu JL. Thymidine kinase 1 combined with CEA, CYFRA21-1 and NSE improved its diagnostic value for lung cancer. Life Sci, 2018, 194: 1-6.
14. 隋静. 肺癌lncRNA生物标志筛选及功能研究. 东南大学, 2020.
15. Huang Y, Qin S, Gu X, et al. Comprehensive assessment of serum hsa_circ_0070354 as a novel diagnostic and predictive biomarker in non-small cell lung cancer. Front Genet, 2022, 12: 796776.
16. Zhu X, Wang X, Wei S, et al. hsa_circ_0013958: A circular RNA and potential novel biomarker for lung adenocarcinoma. FEBS J, 2017, 284(14): 2170-2182.
17. Zhang Y, Zhao H, Zhang L. Identification of the tumor-suppressive function of circular RNA FOXO3 in non-small cell lung cancer through sponging miR-155. Mol Med Rep, 2018, 17(6): 7692-7700.
18. Wu KL, Tsai YM, Lien CT, et al. The roles of microRNA in lung cancer. Int J Mol Sci, 2019, 20(7): 1611.
19. Pan J, Zhou C, Zhao X, et al. A two-miRNA signature (miR-33a-5p and miR-128-3p) in whole blood as potential biomarker for early diagnosis of lung cancer. Sci Rep, 2018, 8(1): 16699.
20. Patnaik S, Mallick R, Kannisto E, et al. MiR-205 and MiR-375 microRNA assays to distinguish squamous cell carcinoma from adenocarcinoma in lung cancer biopsies. J Thorac Oncol, 2015, 10(3): 446-453.
21. Zhang B, Chen Z, Tao B, et al. m6A target microRNAs in serum for cancer detection. Mol Cancer, 2021, 20(1): 170.
22. Califf RM. Biomarker definitions and their applications. Exp Biol Med (Maywood), 2018, 243(3): 213-221.
23. Standfield L, Weston AR, Barraclough H, et al. Histology as a treatment effect modifier in advanced non-small cell lung cancer: A systematic review of the evidence. Respirology, 2011, 16(8): 1210-1220.
24. Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol, 2012, 30(8): 863-870.
25. Shaw AT, Kim TM, Crinò L, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): A randomised, controlled, open-label, phase 3 trial. Lancet Oncol, 2017, 18(7): 874-886.
26. Shaw AT, Solomon BJ, Chiari R, et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: A multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol, 2019, 20(12): 1691-1701.
27. Michels S, Scheel AH, Scheffler M, et al. Clinicopathological characteristics of RET rearranged lung cancer in european patients. J Thorac Oncol, 2016, 11(1): 122-127.
28. Gautschi O, Milia J, Filleron T, et al. Targeting RET in patients with RET-rearranged lung cancers: Results from the global, multicenter RET registry. J Clin Oncol, 2017, 35(13): 1403-1410.
29. Lee SH, Lee JK, Ahn MJ, et al. Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: A phase Ⅱ clinical trial. Ann Oncol, 2017, 28(2): 292-297.
30. Drilon A, Rekhtman N, Arcila M, et al. Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: An open-label, single-centre, phase 2, single-arm trial. Lancet Oncol, 2016, 17(12): 1653-1660.
31. Moosavi F, Giovannetti E, Saso L, et al. HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers. Crit Rev Clin Lab Sci, 2019, 56(8): 533-566.
32. Paik PK, Drilon A, Fan PD, et al. Response to MET inhibitors in patients with stage Ⅳ lung adenocarcinomas harboring MET mutations causing exon 14 skipping. Cancer Discov, 2015, 5(8): 842-849.
33. Wolf J, Seto T, Han JY, et al. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med, 2020, 383(10): 944-957.
34. Clarke JM, George DJ, Lisi S, et al. Immune checkpoint blockade: The new frontier in cancer treatment. Target Oncol, 2018, 13(1): 1-20.
35. Tsoukalas N, Kiakou M, Tsapakidis K, et al. PD-1 and PD-L1 as immunotherapy targets and biomarkers in non-small cell lung cancer. J BUON, 2019, 24(3): 883-888.
36. de Langen AJ, Johnson ML, Mazieres J, et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS^G12C mutation: A randomised, open-label, phase 3 trial. Lancet, 2023, 401(10378): 733-746.
37. Jänne PA, van den Heuvel MM, Barlesi F, et al. Selumetinib plus docetaxel compared with docetaxel alone and progression-free survival in patients with KRAS-mutant advanced non-small cell lung cancer: The SELECT-1 randomized clinical trial. JAMA, 2017, 317(18): 1844-1853.
38. Nikolinakos PG, Altorki N, Yankelevitz D, et al. Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. Cancer Res, 2010, 70(6): 2171-2179.
39. Kim HR, Kang HN, Shim HS, et al. Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma. Ann Oncol, 2017, 28(6): 1250-1259.
40. Ahmadzada T, Kao S, Reid G, et al. An update on predictive biomarkers for treatment selection in non-small cell lung cancer. J Clin Med, 2018, 7(6): 153.
41. Yang H, Liang SQ, Schmid RA, et al. New horizons in KRAS-mutant lung cancer: Dawn after darkness. Front Oncol, 2019, 9: 953.
42. Helsten T, Elkin S, Arthur E, et al. The FGFR landscape in cancer: Analysis of 4, 853 tumors by next-generation sequencing. Clin Cancer Res, 2016, 22(1): 259-267.
43. Thomson S, Petti F, Sujka-Kwok I, et al. Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy. Clin Exp Metastasis, 2008, 25(8): 843-854.
44. Ng TL, Yu H, Smith DE, et al. Preselection of lung cancer cases using FGFR1 mRNA and gene copy number for treatment with ponatinib. Clin Lung Cancer, 2019, 20(1): e39-e51.
45. Provencio M, Ortega AL, Coves-Sarto J, et al. Atezolizumab plus bevacizumab as first-line treatment for patients with metastatic nonsquamous non-small cell lung cancer with high tumor mutation burden: A nonrandomized controlled trial. JAMA Oncol, 2023, 9(3): 344-353.
46. Carbone DP, Reck M, Paz-Ares L, et al. First-line nivolumab in stage Ⅳ or recurrent non-small-cell lung cancer. N Engl J Med, 2017, 376(25): 2415-2426.
47. Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest, 2014, 94(1): 107-116.
48. Qin S, Dong B, Yi M, et al. Prognostic values of TIM-3 expression in patients with solid tumors: A meta-analysis and database evaluation. Front Oncol, 2020, 10: 1288.
49. Cui S, Dong L, Qian J, et al. Classifying non-small cell lung cancer by status of programmed cell death ligand 1 and tumor-infiltrating lymphocytes on tumor cells. J Cancer, 2018, 9(1): 129-134.
50. Kamphorst AO, Pillai RN, Yang S, et al. Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1-targeted therapy in lung cancer patients. Proc Natl Acad Sci U S A, 2017, 114(19): 4993-4998.
51. Zhao P, Li L, Jiang X, et al. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol, 2019, 12(1): 54.
52. Boyiadzis MM, Kirkwood JM, Marshall JL, et al. Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease. J Immunother Cancer, 2018, 6(1): 35.
53. Marchi PD, Berardinelli GN, Cavagna R, et al. Frequency of microsatellite instability (MSI) in Brazilian TKI non-treatable non-small cell lung cancer (NSCLC) patients. J Thorac Oncol, 2019, 14(10): S973.
54. 黄川, 杨雪. 非小细胞肺癌免疫治疗生物标志物的研究进展. 中国肺癌杂志, 2021, 24(11): 777-783.
55. Alexander M, Galeas J, Cheng H. Tumor mutation burden in lung cancer: A new predictive biomarker for immunotherapy or too soon to tell? J Thorac Dis, 2018, 10(Suppl 33): S3994-S3998.
56. 雷芸, 闫春良, 薛旗山, 等. VEGF、VEGFR在NSCLC组织中的表达及临床意义. 癌症进展, 2019, 17(13): 1573-1575.
57. Lin Q, Guo L, Lin G, et al. Clinical and prognostic significance of OPN and VEGF expression in patients with non-small-cell lung cancer. Cancer Epidemiol, 2015, 39(4): 539-544.
58. Wulaningsih W, Holmberg L, Garmo H, et al. Serum lactate dehydrogenase and survival following cancer diagnosis. Br J Cancer, 2015, 113(9): 1389-1396.
59. Mezquita L, Auclin E, Ferrara R, et al. Association of the lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced non-small cell lung cancer. JAMA Oncol, 2018, 4(3): 351-357.
60. Xu F, Lin H, He P, et al. A TP53-associated gene signature for prediction of prognosis and therapeutic responses in lung squamous cell carcinoma. Oncoimmunology, 2020, 9(1): 1731943.
61. Yuan L, Wu X, Zhang L, et al. SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma. Cancer Immunol Immunother, 2022, 71(2): 399-415.
62. Xia L, Mei J, Kang R, et al. Perioperative ctDNA-based molecular residual disease detection for non-small cell lung cancer: A prospective multicenter cohort study (LUNGCA-1). Clin Cancer Res, 2022, 28(15): 3308-3317.
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