Identification and evaluation of COL12A1 as a novel serological diagnostic marker in pancreatic ductal adenocarcinoma

doi:10.3969/j.issn.1674-8115.2025.10.009

Abstract

Abstract:

Objective ·To identify and evaluate novel and reliable non-invasive serological biomarkers for detecting pancreatic ductal adenocarcinoma (PDAC). Methods ·Sixty-seven PDAC patients (Ruijin cohort Ⅰ) were recruited at Pancreatic Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from May 2018 to December 2019. Global proteome profiling of 67 PDAC tumor tissues and 67 matched adjacent normal tissues was performed using mass spectrum. Bioinformatics analysis on the proteomics data was conducted to identify new biomarkers, and receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate their value of detecting PDAC. The proteomic and mRNA sequencing data were further downloaded and analysed from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort for validation. In addition, the Ruijin Cohort Ⅱ, consisting of 47 PDAC patients and 75 healthy individuals, was recruited for a case-control study from June 2021 to June 2022. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression level of new biomarkers in the serum of patients and healthy individuals to evaluate the serological diagnostic values of them. Results ·Collagen type Ⅻ α1 chain (COL12A1) was identified as a candidate biomarker for PDAC diagnosis based on differential expression analysis on the proteomic data and was validated to be higher in tumor tissues than in adjacent normal tissues in the CPTAC cohort. In addition, COL12A1 protein levels were significantly higher in the sera of PDAC patients than in those of healthy controls, showing good diagnostic performance with an AUC of 0.82, a sensitivity of 81%, and a specificity of 83%. ROC analysis revealed that COL12A1 improved the performance of carbohydrate antigen 199 (CA199) in distinguishing PDAC patients from healthy individuals (AUC_CA199=0.91 vs AUC_{CA199 +COL12A1}=0.95, P<0.05). Furthermore, COL12A1 also showed excellent ability to distinguish early-stage PDAC patients (stage Ⅰ‒Ⅱ) from healthy individuals (AUC_COL12A1=0.83), and significantly improved the AUC of CA199 in early-stage PDAC patients (AUC_CA199=0.92 vs AUC_{CA199+COL12A1}=0.97, P<0.05). Conclusion ·COL12A1 is a potential serological diagnostic marker that complements CA199 in detecting early-stage PDAC.

Key words: pancreatic ductal adenocarcinoma (PDAC), collagen type Ⅻ α1 chain (COL12A1), carbohydrate antigen 199 (CA199), diagnosis, proteome

CLC Number:

R735.9

LIU Jia, REN Lingjie, SHI Minmin, TANG Xiaomei, MA Fangfang, QIN Jiejie. Identification and evaluation of COL12A1 as a novel serological diagnostic marker in pancreatic ductal adenocarcinoma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(10): 1342-1352.

Figures/Tables 6

TrendMD

References 36

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Characteristic	Ruijin cohort Ⅰ (n=67)	CPTAC cohort (n=135)	Ruijin cohort Ⅱ			P₂ value^②	P₃ value^③	P₄ value^④
Characteristic	Ruijin cohort Ⅰ (n=67)	CPTAC cohort (n=135)	PDAC (n=47)	Normal (n=75)	P₁ value^①	P₂ value^②	P₃ value^③	P₄ value^④
Age/year	63 (56, 67)	65 (60, 71)	67 (56, 71)	64 (56, 69)	0.317	0.058	0.054	0.375
Gender/n(%)					0.634	0.331	0.810	0.280
Female	33 (49.3)	64 (47.4)	20 (42.6)	37 (49.3)
Male	34 (50.7)	71 (52.6)	27 (57.4)	38 (50.7)
Race/n(%)					‒	<0.001	<0.001	<0.001
Black	0 (0)	2 (1.5)	0 (0)	0 (0)
White	0 (0)	30 (22.2)	0 (0)	0 (0)
Yellow	67 (100)	0 (0)	47 (100)	75 (100)
NA	0 (0)	103 (76.3)	0 (0)	0 (0)
TNM stage/n(%)					‒	<0.001	<0.001	0.380
Ⅰ	20 (29.9)	23 (17.0)	5 (10.6)	‒
Ⅱ	47 (70.1)	56 (41.5)	17 (36.2)	‒
Ⅲ	0 (0)	41 (30.4)	18 (38.3)	‒
Ⅳ	0 (0)	9 (6.7)	7 (14.9)	‒
NA	0 (0)	6 (4.4)	0 (0)	‒
T stage/n(%)					‒	0.185	0.120	0.720
T1	10 (14.9)	10 (7.4)	4 (8.5)	‒
T2	20 (29.9)	83 (61.5)	20 (42.6)	‒
T3	37 (55.2)	39 (28.9)	7 (14.9)	‒
T4	0 (0)	1 (0.7)	16 (34.0)	‒
TX	0 (0)	2 (1.5)	0 (0)	‒
N stage/n(%)					‒	<0.001	<0.001	0.043
N0	44 (65.7)	30 (22.2)	12 (25.5)	‒
N1	23 (34.3)	51 (37.8)	18 (38.3)	‒
N2	0 (0)	46 (34.1)	14 (29.8)	‒
NX	0 (0)	8 (5.9)	3 (6.4)	‒
M stage/n(%)					‒	<0.001	<0.001	0.001
M0	67 (100)	88 (65.2)	40 (85.1)	‒
M1	0 (0)	8 (5.9)	7 (14.9)	‒
MX	0 (0)	39 (28.9)	0 (0)	‒

Characteristic	Ruijin cohort Ⅰ (n=67)	CPTAC cohort (n=135)	Ruijin cohort Ⅱ			P₂ value^②	P₃ value^③	P₄ value^④
Characteristic	Ruijin cohort Ⅰ (n=67)	CPTAC cohort (n=135)	PDAC (n=47)	Normal (n=75)	P₁ value^①	P₂ value^②	P₃ value^③	P₄ value^④
Age/year	63 (56, 67)	65 (60, 71)	67 (56, 71)	64 (56, 69)	0.317	0.058	0.054	0.375
Gender/n(%)					0.634	0.331	0.810	0.280
Female	33 (49.3)	64 (47.4)	20 (42.6)	37 (49.3)
Male	34 (50.7)	71 (52.6)	27 (57.4)	38 (50.7)
Race/n(%)					‒	<0.001	<0.001	<0.001
Black	0 (0)	2 (1.5)	0 (0)	0 (0)
White	0 (0)	30 (22.2)	0 (0)	0 (0)
Yellow	67 (100)	0 (0)	47 (100)	75 (100)
NA	0 (0)	103 (76.3)	0 (0)	0 (0)
TNM stage/n(%)					‒	<0.001	<0.001	0.380
Ⅰ	20 (29.9)	23 (17.0)	5 (10.6)	‒
Ⅱ	47 (70.1)	56 (41.5)	17 (36.2)	‒
Ⅲ	0 (0)	41 (30.4)	18 (38.3)	‒
Ⅳ	0 (0)	9 (6.7)	7 (14.9)	‒
NA	0 (0)	6 (4.4)	0 (0)	‒
T stage/n(%)					‒	0.185	0.120	0.720
T1	10 (14.9)	10 (7.4)	4 (8.5)	‒
T2	20 (29.9)	83 (61.5)	20 (42.6)	‒
T3	37 (55.2)	39 (28.9)	7 (14.9)	‒
T4	0 (0)	1 (0.7)	16 (34.0)	‒
TX	0 (0)	2 (1.5)	0 (0)	‒
N stage/n(%)					‒	<0.001	<0.001	0.043
N0	44 (65.7)	30 (22.2)	12 (25.5)	‒
N1	23 (34.3)	51 (37.8)	18 (38.3)	‒
N2	0 (0)	46 (34.1)	14 (29.8)	‒
NX	0 (0)	8 (5.9)	3 (6.4)	‒
M stage/n(%)					‒	<0.001	<0.001	0.001
M0	67 (100)	88 (65.2)	40 (85.1)	‒
M1	0 (0)	8 (5.9)	7 (14.9)	‒
MX	0 (0)	39 (28.9)	0 (0)	‒