血清纤维连接蛋白在非小细胞肺癌患者中的表达水平及其临床应用价值

doi:10.3969/j.issn.1006-5725.2025.10.016

Abstract

Abstract:

Objective To investigate the expression levels of serum fibronectin （FN） in patients with non-small cell lung cancer （NSCLC） and evaluate its clinical diagnostic significance. Methods Firstly， the gene and tissue protein expression levels of FN in NSCLC were assessed using the TIMER2.0 database， GTEx database， and Human Protein Atlas （HPA） database. Secondly， from January 2021 to June 2023， a total of 154 patients with lung space-occupying lesions or shadows at the First Affiliated Hospital of Anhui University of Chinese Medicine were enrolled. Based on medical history， clinical manifestations， imaging tests， and pathological histological findings， these patients were categorized into two groups： 81 patients with NSCLC and 73 patients with benign lung diseases. The serum concentration of FN was measured by immunoturbidimetry， while the serum levels of CEA， SCC， and CYFRA21-1 were determined using chemiluminescence. Results The bioinformatics analysis results demonstrated that the gene expression and tissue protein levels of FN were significantly reduced compared to normal tissues. In serological evaluations， serum FN concentrations in patients with advanced NSCLC （Stage Ⅲ-Ⅳ） and early-stage NSCLC （Stage Ⅰ-Ⅱ）（249.50 ng/mL and 305.00 ng/mL， respectively） were markedly lower than those observed in the benign lung disease group （429.16 ng/mL）（P < 0.001）. Univariate and multivariate logistic regression analyses indicated that serum FN could serve as a significant predictor for the presence of NSCLC. The area under the receiver operating characteristic curve （ROC） for serum FN in diagnosing early-stage NSCLC was 0.790， which outperformed CEA （0.618）， SCC （0.653）， and CYFRA21-1 （0.601）. The optimal critical concentration of serum FN for distinguishing early-stage NSCLC from benign diseases was determined to be 347.6 ng/mL， with a sensitivity of 71.93%， surpassing that of CEA （19.30%）， SCC （12.28%）， and CYFRA21-1 （8.77%）. Conclusion Serum FN is significantly downregulated in NSCLC and may serve as a potential biomarker for the early diagnosis of NSCLC.

Key words: NSCLC, Fibronectin, CEA, SCC, CYFRA21-1

CLC Number:

R446.6

Qingbao WANG,Shouhui CHEN,Yating LIU,Jun ZHU,Boke. ZHANG. The expression level of serum fibronectin in patients with non⁃small cell lung cancer and its clinical application value[J]. The Journal of Practical Medicine, 2025, 41(10): 1540-1547.

Figures/Tables 8

Tab.1

Fig.1

Tab.2

Peripheral blood biomarker levels in patients with NSCLC and Bengin lung disease"

标志物	肺良性疾病组	NSCLC组	t/Z值	P值
FN（ $x ˉ$ ± s）/（ng/mL）	429.16 ± 110.67	304.35 ± 73.21	-8.329	< 0.001
CEA/（ng/mL）	1.65（1.19，2.57）	2.68（1.52，6.79）	4.042	< 0.001
SCC/（ng/mL）	0.60（0.45，0.85）	0.90（0.60，1.45）	3.970	< 0.001
CYFRA21-1/（ng/mL）	1.40（1.02，1.75）	1.68（1.30，5.89）	4.127	< 0.001

Tab.2

Fig.2

Tab.3

Tab.4

Fig.3

Tab.5

References 27

1	FREDDIE B， MATHIEU L， HYUNA S， et al. Global cancer statistics 2022： GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］. CA Cancer J Clin， 2024， 74（3）：229-263. doi:10.3322/caac.21834 doi: 10.3322/caac.21834
2	BORG M， KRISTENSEN K， ALSTRUP G， et al. Consequences of Losing Incidental Pulmonary Nodules to Follow-Up： Unmonitored Nodules Progressing to Stage IV Lung Cancer［J］. Respiration， 2024， 103（2）：53-59. doi:10.1159/000535595 doi: 10.1159/000535595
3	CHUTIVANIDCHAYAKUL F， SUWATANAPONGCHED T， PETNAK T. Clinical and chest radiographic features of missed lung cancer and their association with patient outcomes［J］. Clin Imaging， 2023， 99：73-81. doi:10.1016/j.clinimag.2023.03.017 doi: 10.1016/j.clinimag.2023.03.017
4	FU R， SUN K， WANG X， et al. Survival differences between the USA and an urban population from China for all cancer types and 20 individual cancers： A population-based study［J］. Lancet Reg Health West Pac， 2023， 37：100799. doi:10.1016/j.lanwpc.2023.100799 doi: 10.1016/j.lanwpc.2023.100799
5	RELLI V， TREROTOLA M， GUERRA E， et al. Abandoning the Notion of Non-Small Cell Lung Cancer［J］. Trends Mol Med， 2019， 25（7）：585-594. doi:10.1016/j.molmed.2019.04.012 doi: 10.1016/j.molmed.2019.04.012
6	陈刚，史少明，邢雅军，等. 非小细胞肺癌患者外周血中lncRNA SNHG5的表达及诊断意义［J］. 实用医学杂志， 2019， 35（22）：3457-3462.
7	MAO H， LIANG M， HONGBO J， et al. Diagnostic value of aberrant decreased 5-Methylcytosine RNA modification in leukocytes for non-small cell lung cancer［J］. J Cancer， 2023， 14（12）：2198-2208. doi:10.7150/jca.85681 doi: 10.7150/jca.85681
8	王海英，吴凯，田胤纯. 血清基质金属蛋白酶-9、细胞角蛋白19片段及血管内皮细胞生长因子水平与非小细胞肺癌患者顺铂治疗效果的关系［J］. 实用医学杂志， 2024， 40（24）：3452-3457.
9	MINGXIANG F， XIN Y， BAISHEN C， et al. Detection of circulating genetically abnormal cells using 4-color fluorescence in situ hybridization for the early detection of lung cancer［J］. J Cancer Res Clin Oncol， 2021， 147（8）：2397-2405. doi:10.1007/s00432-021-03517-6 doi: 10.1007/s00432-021-03517-6
10	JIRI K， ANNA Z. Role of fibronectin in chronic venous diseases： A review［J］. Vasc Med， 2020， 25（6）：588-597. doi:10.1177/1358863x20947789 doi: 10.1177/1358863x20947789
11	RUSSO T A， BANUTH A M M， NADER H B， et al. Altered shear stress on endothelial cells leads to remodeling of extracellular matrix and induction of angiogenesis［J］. PLoS One， 2020， 15（11）：e0241040. doi:10.1371/journal.pone.0241040 doi: 10.1371/journal.pone.0241040
12	ZHOU F， SUN J， YE L， et al. Fibronectin promotes tumor angiogenesis and progression of non-small-cell lung cancer by elevating WISP3 expression via FAK/MAPK/ HIF-1α axis and activating wnt signaling pathway［J］. Exp Hematol Oncol， 2023， 12（1）：61. doi:10.1186/s40164-023-00419-w doi: 10.1186/s40164-023-00419-w
13	ZHANG L， WANG Y， SONG M， et al. Fibronectin 1 as a Key Gene in the Genesis and Progression of Cadmium-Related Bladder Cancer［J］. Biol Trace Elem Res， 2023， 201（9）：4349-4359. doi:10.1007/s12011-022-03510-1 doi: 10.1007/s12011-022-03510-1
14	TAS F， BILGIN E， KARABULUT S， et al. Levels of serum fibronectin as a biomarker in gastric cancer patients： Correlation with clinical diagnosis and outcome［J］. Mol Clin Oncol， 2016， 4（4）：655-659. doi:10.3892/mco.2016.759 doi: 10.3892/mco.2016.759
15	AN T， QIN S， SUN D， et al. Unique Protein Profiles of Extracellular Vesicles as Diagnostic Biomarkers for Early and Advanced Non-Small Cell Lung Cancer［J］. Proteomics， 2019， 19（12）：e1800160. doi:10.1002/pmic.201800160 doi: 10.1002/pmic.201800160
16	ZHOU M， KONG Y， WANG X， et al. LC-MS/MS-Based Quantitative Proteomics Analysis of Different Stages of Non-Small-Cell Lung Cancer［J］. Biomed Res Int， 2021， 2021：5561569. doi:10.1155/2021/5561569 doi: 10.1155/2021/5561569
17	MAO J， FENG Y， ZHENG Y， et al. GPR65 inhibits human trophoblast cell adhesion through upregulation of MYLK and downregulation of fibronectin via cAMP-ERK signaling in a low pH environment［J］. Cell Commun Signal， 2023， 21（1）：238. doi:10.1186/s12964-023-01249-3 doi: 10.1186/s12964-023-01249-3
18	XU W， HE M， LU Q. Fibronectin Connecting Cell Sheet Based on Click Chemistry for Wound Repair［J］. Adv Sci （Weinh）， 2024， 11（11）：e2306746. doi:10.1002/advs.202306746 doi: 10.1002/advs.202306746
19	YUAN X， WU Y， LIN J， et al. Plasma fibronectin can affect the cytokine profile and monocytes/macrophages function in addition to predicting the prognosis of advanced sepsis［J］. FASEB J， 2022， 36（3）：e22179. doi:10.1096/fj.202100760rrr doi: 10.1096/fj.202100760rrr
20	TAKEYAMA H， YOSHINOBU M. Serum Sialyl Fibronectin Is an Indicator of Good Prognosis in Thyroid Cancer［J］. Cancer Diagn Progn， 2023， 3（1）：75-84. doi:10.21873/cdp.10182 doi: 10.21873/cdp.10182
21	KIM H， PARK J， KIM Y， et al. Serum fibronectin distinguishes the early stages of hepatocellular carcinoma［J］. Sci Rep， 2017， 7（1）：9449. doi:10.1038/s41598-017-09691-3 doi: 10.1038/s41598-017-09691-3
22	CHRISTINE B， HOLGER K， SIMON L G， et al. Integrins and their ligands are expressed in non-small cell lung cancer but not correlated with parameters of disease progression［J］. Virchows Arch， 2013， 464（1）：69-78. doi:10.1007/s00428-013-1506-1 doi: 10.1007/s00428-013-1506-1
23	MING J X， WANG Z C， HUANG Y， et al. Fucoxanthin extracted from Laminaria Japonica inhibits metastasis and enhances the sensitivity of lung cancer to Gefitinib［J］. J Ethnopharmacol， 2021， 265：113302. doi:10.1016/j.jep.2020.113302 doi: 10.1016/j.jep.2020.113302
24	CAVUS B， AKYUZ F， ILIAZ R.， et al. Assessment of prognostic and diagnostic value of some biomarkers in hepatocellular carcinoma［J］. Exp Oncol， 2020， 42（3）：208-214.
25	SUN J， CHEN X， WANG Y. Comparison of the diagnostic value of CEA combined with OPN or DKK1 in non-small cell lung cancer［J］. Oncol Lett， 2020， 20（3）：3046-3052. doi:10.3892/ol.2020.11846 doi: 10.3892/ol.2020.11846
26	JIANG C， ZHAO M， HOU S， et al. The Indicative Value of Serum Tumor Markers for Metastasis and Stage of Non-Small Cell Lung Cancer［J］. Cancers （Basel）， 2022， 14（20）：5064. doi:10.3390/cancers14205064 doi: 10.3390/cancers14205064
27	LIAO X， LIU M， LI S， et al. The value on SUV-derived parameters assessed on F-FDG PET/CT for predicting mediastinal lymph node metastasis in non-small cell lung cancer［J］. BMC Med Imaging， 2023， 23（1）：49. doi:10.1186/s12880-023-01004-7 doi: 10.1186/s12880-023-01004-7

临床变量	肺良性疾病组（n = 73）	NSCLC组（n = 81）	t/χ² 值	P值
年龄（x ± s）/岁	57.82 ± 11.31	61.82 ± 12.72	2.056	0.042
性别（男/女）	37/36	48/33	1.141	0.285
吸烟史（有/无）	22/51	30/51	0.817	0.366
组织学类型			-	-
肺部良性结节	29
炎性病变	37
肺结节病	2
间质性肺病	2
其他	3
肺腺癌		61
肺鳞状细胞癌		20

标志物	β	SE	Wald χ²	OR	95%CI	P 值
年龄	0.010	0.020	0.238	1.010	0.971 ~ 1.051	0.626
FN	-0.016	0.004	19.696	0.984	0.977 ~ 0.991	< 0.001
CEA	0.235	0.143	2.682	1.264	0.955 ~ 1.674	0.101
SCC	0.399	0.575	0.483	1.490	0.483 ~ 4.596	0.487
CYFRA21-1	0.237	0.200	1.403	1.268	0.856 ~ 1.878	0.236

标志物	AUC	P值	敏感度/%	特异度/%
FN^?	0.790（0.713 ~ 0.800）	< 0.001	71.93	71.23
CEA^?	0.618（0.519 ~ 0.717）	0.021	19.30	95.89
SCC^?	0.653（0.559 ~ 0.747）	0.003	12.28	94.52
CYFRA21-1^?	0.601（0.504 ~ 0.699）	0.048	8.77	98.63
FN^#	0.837（0.776 ~ 0.898）	< 0.001	80.25	71.23
CEA^#	0.689（0.606 ~ 0.772）	< 0.001	29.63	95.89
SCC^#	0.685（0.602 ~ 0.767）	< 0.001	24.69	94.52
CYFRA21-1^#	0.693（0.611 ~ 0.775）	< 0.001	30.86	91.78

临床特征	例数	FN	t值	P值
年龄（岁）			0.845	0.401
< 60	32	313.35 ± 68.45
≥ 60	49	299.54 ± 74.03
吸烟史			0.864	0.390
无	51	310.29 ± 71.65
有	30	296.00 ± 72.26
肿瘤大小			3.627	0.001
< 3.0 cm	54	324.05 ± 65.94
≥ 3.0 cm	27	266.89 ± 68.70
TNM分期			5.199	< 0.001
Ⅰ-Ⅱ	57	328.36 ± 61.85
Ⅲ-Ⅳ	24	249.50 ± 63.51
淋巴结转移			4.169	< 0.001
无	56	325.23 ± 63.39
有	25	259.67 ± 69.72
远处转移			4.173	< 0.001
无	66	319.45 ± 66.47
有	15	241.43 ± 59.98
组织学类型			-1.118	0.267
肺鳞癌	20	289.45 ± 72.71
肺腺癌	61	310.09 ± 71.31

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The expression level of serum fibronectin in patients with non⁃small cell lung cancer and its clinical application value

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