Plasma Matrix Metalloproteinase-1 as a Prognostic Biomarker in Oral Cavity Squamous Cell Carcinoma

Figures & data

Table 1 Clinical Characteristics of Patients with Oral Cavity Squamous Cell Carcinoma (OSCC) and Oral Premalignant Disease (OPMD)

Characteristics	OSCC n = 401	OPMD n = 276
Age (years) ^†	55.4 ± 11.1^† (89.7, 28.5)	52.5 ± 11.7^† (86.6, 25.6)
Gender
Male	367 (91.5%)	252 (91.3%)
Female	34 (8.5%)	24 (8.7%)
Alcohol consumption
(-)	142 (35.4%)	96 (34.8%)
(+)	259 (64.6%)	180 (65.2%)
Betel nut chewing
(-)	70 (17.5%)	74 (26.8%)
(+)	331 (52.5%)	202 (73.2%)
Cigarettes (smoking)
(-)	64 (16.0%)	33 (12.0%)
(+)	337 (84.0%)	243 (88.0%)
Lesion site
Tongue	149 (37.2%)
Buccal mucosa	159 (39.7%)
Gum	54 (13.5%)
Mouth floor	22 (5.4%)
Lip	12 (3.0%)
Hard palate	5 (1.2%)
pT classification
1	93 (23.2%)
2	127 (31.7%)
3	46 (11.4%)
4	135 (33.7%)
pN classification
(-)	257 (64.1%)
(+)	144 (35.9%)
Overall stage
I	77 (19.2%)
II	88 (22.0%)
III	55 (13.7%)
IV	181 (45.1%)

Note: ^†Mean ± SD (maximum, minimum).

Figure 1 Plasma matrix metalloproteinase-1 (MMP-1) levels from 677 specimens. (A) Significantly higher plasma MMP-1 levels in oral squamous cell carcinoma (OSCC) than oral potentially malignant disorders (OPMD). (B) Receiver operating characteristic curve for OSCC versus OPMD.

Table 2 Associations of MMP1 Protein Concentrations in Plasma with Clinicopathological Characteristics

	Plasma MMP1 Expression
Characteristics	< 2018 pg/mL^‡	≥ 2018 pg/mL	P value
Alcohol consumption
(-)	63 (31.5%)	79 (39.3%)	0.102
(+)	137 (68.5%)	122 (60.7%)
Betel nut chewing
(-)	33 (16.5%)	37 (18.4%)	0.614
(+)	167 (83.5%)	164 (81.6%)
Cigarettes (smoking)
(-)	25 (12.5%)	39 (19.4%)	0.059
(+)	175 (87.5%)	162 (80.6%)
pT Status
1–2	135 (67.5%)	85 (42.3%)	< 0.001*
3–4	65 (32.5%)	116 (57.7%)
pN Status
(-)	130 (65.0%)	127 (63.2%)	0.704
(+)	70 (35.0%)	74 (36.8%)
Overall Pathological Stage
I–II	97 (48.5%)	68 (33.8%)	0.003*
III–IV	103 (51.5%)	133 (66.2%)
Extranodal extension
(-)	165 (82.5%)	149 (74.1%)	0.042*
(+)	35 (17.5%)	52 (25.9%)
Lymphovascular invasion
(-)	187 (93.5%)	176 (87.6%)	0.042*
(+)	13 (6.5%)	25 (12.4%)
Cell Differentiation^†
W-D+M-D	178 (89.0%)	182 (90.6%)	0.609
P-D	22 (11.0%)	19 (9.4%)
Bone Invasion
No	171 (85.5%)	165 (82.1%)	0.354
Yes	29 (14.5%)	36 (17.9%)

Note: *Statistically significant. ^‡Median value of all OSCC patients.

Abbreviations: ^†W-D, well-differentiated; M-D, moderately differentiated; P-D, poorly differentiated.

Figure 2 Comparisons of plasma matrix metalloproteinase-1 (MMP-1) levels in oral squamous cell carcinoma patients. Associations of plasma MMP-1 levels with (A) age, (B) gender, (C) tumor depth, (D) pT, (E) pN, and (F) overall stage.

Table 3 Multivariate Analysis of Survival Analyses Stratified by the Median MMP1 Concentration (≥2018 Pg/mL Vs <2018 Pg/Ml) in 394 Patients with Oral Cavity Squamous Cell Carcinoma

Prognostic Endpoint	Hazard Ratio^†	95% CI	P value
Overall survival	1.583	1.062–2.358	0.024*
Disease-specific survival	1.420	0.913–2.209	0.119
Disease-free survival	1.505	1.051–2.154	0.025*
Locoregional recurrence-free survival	1.406	0.978–2.023	0.066
Distant metastasis-free survival	1.688	1.139–2.502	0.009*

Notes: *statistically significant. ^†Hazard ratios were adjusted by age, sex, overall pathological stage (stage III~IV vs I~II), pathological N status (N+ vs N0), extranodal extension (positive vs negative), perineural invasion (positive vs negative), lymphovascular invasion (positive vs negative), surgical margin (< 5mm vs ≥ 5mm), histological differentiation (poor differentiation vs well and moderate differentiation), and bone invasion (positive vs negative).

Figure 3 Kaplan–Meier plot of 394 patient stratified by median value of plasma matrix metalloproteinase-1 levels (2018 pg/mL) (A) overall survival (B) disease-specific survival (C) disease-free survival (D) locoregional recurrence-free survival (E) distant metastasis-free survival.