Evaluation of diagnostic value of novel blood-derived biomarkers for active pulmonary tuberculosis

doi:10.19982/j.issn.1000-6621.20250380

Abstract

Abstract:

Objective: To evaluate the diagnostic value of tuberculosis-specific biomarkers in peripheral blood for active pulmonary tuberculosis (PTB). Methods: In a prospective study, peripheral blood samples were collected from 10 patients with active PTB (PTB sequencing group) and 10 healthy individuals (control sequencing group) admitted to the Tuberculosis Department of Shanghai Pulmonary Hospital between June and July 2024 for transcriptome sequencing to screen for potential diagnostic target genes. Subsequently, from February to October 2025, peripheral blood samples were collected from 69 PTB patients (TB validation group), 22 non-TB patients (non-TB validation group), and 58 healthy individuals (control validation group) was used to measure. The mRNA expression levels of candidate genes in peripheral blood were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic value of the identified biomarkers for active PTB was assessed by calculating sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) against the final clinical diagnosis reference standard. Results: Sixteen candidate genes were identified by transcriptomic sequencing of peripheral blood. After qRT-PCR validation, three biomarkers with upregulated expression levels were identified: TRIM22, FKBP9, and ERRFI1. Compared to the control validation group, the expression levels of all three markers were significantly higher in the TB validation group (TRIM22: 42.32 vs. 14.53; FKBP9: 6.41 vs. 0.20; ERRFI1: 5.70 vs. 0.44), with statistically significant differences (Z=-5.030, -4.425, -6.044, respectively; all P<0.05). Compared to the control validation group, ROC curve analysis revealed that TRIM22 demonstrated a sensitivity, specificity, and AUC of 80.00%, 91.38%, and 0.956, respectively; FKBP9 had 98.44%, 91.67%, and 0.769, respectively; and ERRFI1 had 94.29%, 97.76%, and 0.819. The diagnostic performance did not improve significantly when the three genes were used in combination (AUC=0.796). When compared to non-TB patients, only ERRFI1 showed diagnostic value in distinguishing active PTB, with a sensitivity of 87.76%, specificity of 98.28%, and an AUC of 0.972. Conclusion: The peripheral blood levels of TRIM22, FKBP9, and ERRFI1 in patients with active PTB can effectively distinguish them from healthy individuals, showing promising diagnostic potential. These markers may serve as novel targets for the diagnosis of active PTB.

Key words: Tuberculosis, pulmonary, Biological markers, Bulk transcriptome sequencing, Diagnosis

CLC Number:

Zhang Yujie, Zhou Jie, Wang Yun, Fan Lin. Evaluation of diagnostic value of novel blood-derived biomarkers for active pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2026, 48(3): 320-328. doi: 10.19982/j.issn.1000-6621.20250380

Figures/Tables 7

References 31

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基因(人)	前引物	后引物
β-actin	5'-CCTGGACTTCGAGCAAGAGATGG-3'	5'-CAGGAAGGAAGGCTGGAAGAGTG-3'
ETV5	5'-TCAGCAAGTCCCTTTTATGGTC-3'	5'-GCTCTTCAGAATCGTGAGCCA-3'
CDKL3	5'-TTCATCACGAAAACCTGGTCAA-3'	5'-AAGTCGCTTACTCTCTAGTCCAT-3'
AJUBA	5'-ATGGGGAAGTCCTATCATCCAG-3'	5'-TGGTAGTCGGTGACACAGTAT-3'
P4HA2	5'-CAAACTGGTGAAGCGGCTAAA-3'	5'-GCACAGAGAGGTTGGCGATA-3'
CFB	5'-GCGATCTGTGACAACGGAG-3'	5'-GCTGTCTTCAAGGCGGTACT-3'
LIPT2	5'-CTGACGCCCGAGGAAACTG-3'	5'-GTGGGATGTGATGTGCCTTC-3'
TUBB3	5'-GGCCAAGGGTCACTACACG-3'	5'-GCAGTCGCAGTTTTCACACTC-3'
BEND7	5'-CTGGATCAAACTGCTGTACTTG-3'	5'-GGGAAATTGGAGGTTGTTGTCTG-3'
DDAH1	5'-CAAAAGGACAAATCAACGAGGT-3'	5'-TGTGCAGATTCACTAGACCCAA-3'
KLHL23	5'-ATGCCACGGAAAGGATATACCT-3'	5'-CAACACCTGAGGACCAAACTAC-3'
MOK	5'-CCGGAGTGTCTCCTCACTGAT-3'	5'-CAGACTGGCGATCTCGTAGAA-3'
DOCK6	5'-GCTTCTGGAGACGAGAGGTC-3'	5'-AGGTTCCTCAGGTCGAAGATG-3'
FKBP9	5'-CAGGTGTCTGATTTTGTGAGGT-3'	5'-TTCATGCGATTGTGACTCGAA-3'
TG	5'-AGGGAGAGTTTATGCCTGTCC-3'	5'-CAATACCCAGATACCTCAGGGA-3'
ERRFI1	5'-GACCCACCGAAGATTAAGAAGG-3'	5'-GGTCTAGGAGGTATGGGAACTCT-3'
TRIM22	5'CTGTCCTGTGTGTCAGACCAG-3'	5'TGTGGGCTCATCTTGACCTCT-3'

基因	健康验证组 (58例)	结核验证组		Z值	P值
基因	健康验证组 (58例)	病原学阳性(35例)	病原学阴性(34例)	Z值	P值
ETV5	0.87(0.48,2.65)	0.18(0.14,0.29)	0.11(0.09,0.47)	4.543	0.077
CDKL3	0.94(0.50,3.09)	0.22(0.17,0.38)	0.36(0.13,0.70)	3.938	0.008
AJUBA	0.40(0.13,1.53)	0.22(0.14,0.35)	0.44(0.29,0.90)	0.379	0.557
P4HA2	0.05(0.02,0.09)	0.02(0.02,0.03)	0.04(0.03,0.06)	3.009	0.002
CFB	0.86(0.35,5.05)	0.29(0.09,0.45)	0.37(0.11,0.56)	2.857	0.323
LIPT2	0.37(0.15,1.03)	0.39(0.32,0.57)	0.40(0.29,0.77)	-0.729	0.647
TUBB3	0.44(0.18,1.42)	0.34(0.18,0.94)	0.45(0.20,1.69)	0.076	0.543
DDAH1	0.30(0.09,1.68)	0.07(0.05,0.10)	0.08(0.05,0.13)	3.304	0.327
KLHL23	1.69(0.79,3.96)	0.02(0.01,0.04)	0.03(0.00,0.07)	6.044	<0.001
BEND7	1.30(0.72,3.72)	6.11(3.86,17.81)	4.36(2.68,12.57)	-4.007	0.911
MOK	0.55(0.21,1.53)	0.31(0.12,0.45)	0.45(0.16,0.63)	1.003	0.752
DOCK6	0.19(0.10,0.35)	0.07(0.05,0.13)	0.08(0.06,0.12)	3.498	0.044
FKBP9	0.20(0.11,0.49)	6.41(4.05,12.32)	5.70(2.54,7.40)	-4.425	0.007
TG	0.27(0.15,0.51)	0.23(0.13,0.36)	0.26(0.15,0.40)	1.065	0.248
ERRGI1	0.44(0.17,1.37)	5.70(3.05,13.46)	5.57(2.95,7.38)	-6.044	0.002
TRIM22	14.53(12.40,15.45)	42.32(29.75,72.16)	43.69(32.85,64.09)	-5.030	<0.001

指标	最佳界值	敏感度(%)	特异度(%)	AUC值
TRIM22
肺结核患者	22.60	80.00	91.38	0.956
病原学阴性	32.33	98.21	93.79	0.896
病原学阳性	32.63	97.21	93.79	0.958
FKBP9
肺结核患者	0.201	98.44	91.67	0.769
病原学阴性	0.206	95.83	86.02	0.731
病原学阳性	3.754	82.35	91.38	0.894
ERRFI1
肺结核患者	0.095	94.29	97.76	0.819
病原学阴性	1.184	85.11	75.86	0.842
病原学阳性	3.542	70.59	94.83	0.838
联合检测
肺结核患者	0.545	88.24	76.11	0.796
病原学阴性	0.685	98.53	97.23	0.848
病原学阳性	0.005	80.39	98.23	0.885

基因	Non-TB组	TB(MTB阳性)组	TB(MTB阴性)组	Z值	P值^a	Z值	P值^b	Z值	P值^c
TRIM22	42.32(30.84,60.16)	42.33(29.76,70.86)	43.15(32.85,88.45)	2.279	0.651	4.507	0.528	1.977	0.778
FKBP9	8.85(3.46,12.42)	5.77(3.84,12.15)	5.70(2.54,7.40)	1.826	0.349	3.362	0.058	1.841	0.085
ERRFI1	0.86(0.23,4.46)	6.41(4.05,12.32)	5.32(2.89,7.47)	1.784	0.001	2.152	0.005	1.672	0.095