{"id":769350,"date":"2026-06-29T18:14:27","date_gmt":"2026-06-29T18:14:27","guid":{"rendered":"https:\/\/www.newsbeep.com\/ca\/769350\/"},"modified":"2026-06-29T18:14:27","modified_gmt":"2026-06-29T18:14:27","slug":"plasma-col3a1-propeptide-as-a-promising-prognostic-marker-in-oral-squamous-cell-carcinoma","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/ca\/769350\/","title":{"rendered":"Plasma COL3A1 propeptide as a promising prognostic marker in oral squamous cell carcinoma"},"content":{"rendered":"

Plasma protein levels<\/p>\n

Among the proteins measured on the Olink Explore 3072 platform, 11 collagen-derived peptides were detected in plasma from patients and controls (COL1A1, COL2A1, COL3A1, COL4A1, COL5A1, COL6A3, COL9A1, COL15A1, COL18A1, COL24A1, COL28A1). When comparing plasma protein levels between patients and controls, no significant differences were seen (Fig.\u00a01<\/a>).<\/p>\n

Fig. 1\"Fig.<\/p>\n

Plasma levels of collagen turnover markers in patients and controls are shown as box plots of normalised protein expression (NPX) levels.<\/p>\n

Comparison of plasma collagen levels with clinical parameters<\/p>\n

We next investigated whether collagen-derived peptide levels vary with age, sex, tumour size, and lymph node status. Seven peptides (COL1A1, COL2A1, COL3A1, COL5A1, COL6A3, COL9A1, and COL18A1) were significantly associated with age (p\u2009<\u20090.05), with the highest correlation seen for COL18A1 (Spearman\u2019s rho\u2009=\u20090.538). When comparing early-stage (T1\u2009+\u2009T2) and advanced-stage disease (T3\u2009+\u2009T4) of OSCC, COL24A1 levels were significantly higher in T1\u2009+\u2009T2 than in T3\u2009+\u2009T4 tumours (p\u2009=\u20090.002). No significant differences in collagen peptide levels were observed based on sex or cervical lymph node status (Table S4<\/a>).<\/p>\n

Impact of plasma collagen protein levels on survival outcome<\/p>\n

To investigate whether plasma peptide levels influenced the overall survival (OS) and disease-free survival (DFS), OSCC patients were stratified into high and low groups based on the median protein level, and Kaplan-Meier survival analysis with the log-rank test was performed. Patients with high plasma levels of COL3A1 propeptides demonstrated significantly longer OS than those with low protein levels over a 12-year follow-up time (p\u2009=\u20090.0046; Fig.\u00a02<\/a>a). Similarly, high COL3A1 propeptide levels were associated with significantly longer DFS (p\u2009=\u20090.00054; Fig.\u00a02<\/a>b). Variations in plasma levels of the other 10 collagen peptides did not significantly affect OS or DFS (data not shown).<\/p>\n

Fig. 2\"Fig.<\/p>\n

Kaplan-Meier plots showing the association of plasma COL3A1 levels with survival. (a) Overall survival; (b) disease-free survival. Patients were stratified into high- and low-groups based on the median COL3A1 level. Survival differences were assessed using the log-rank test.<\/p>\n

Following the observation that elevated plasma levels of COL3A1 propeptides were associated with improved survival, multivariate analyses were conducted to evaluate their independent prognostic significance alongside established clinicopathological parameters (age, sex, tumour size, and nodal status). As shown in Table\u00a01<\/a>, Cox proportional hazards regression analysis demonstrated that high plasma levels of COL3A1 propeptides were independently associated with better OS (p\u2009=\u20090.007, hazard ratio\u2009=\u20090.169, 95% confidence interval\u2009=\u20090.046\u20130.618) and DFS (p\u2009<\u20090.001, hazard ratio\u2009=\u20090.105, 95% confidence interval\u2009=\u20090.028\u20130.399).<\/p>\n

Table 1 Multivariate Cox proportional hazards regression analysis.<\/p>\n

LASSO-penalised Cox regression with COL3A1, age, sex, tumour size, and nodal status as candidate variables retained COL3A1, tumour size, and nodal status in the models for both OS and DFS (Table\u00a02<\/a>). For OS, higher COL3A1 level was associated with a reduced risk of death (hazard ratio\u2009=\u20090.33), whereas larger tumour size (hazard ratio\u2009=\u20091.39) and positive nodal status (hazard ratio\u2009=\u20091.31) were associated with increased risk. For DFS, higher COL3A1 level was similarly associated with a reduced risk of recurrence (hazard ratio\u2009=\u20090.23), while larger tumour size (hazard ratio\u2009=\u20091.40) and positive nodal status (hazard ratio\u2009=\u20091.38) were associated with increased risk.<\/p>\n

Table 2 LASSO-Penalised Cox Results.Plasma proteomic differences between COL3A1-low and COL3A1-high patients<\/p>\n

To assess the functional relevance of COL3A1 levels in relation to survival, plasma proteomic profiles were compared between COL3A1-low and COL3A1-high patients. Age-adjusted generalised linear modelling identified 112 proteins with p\u2009<\u20090.05, however, only COL3A1 remained significant after multiple testing correction (adjusted p\u2009<\u20090.05, Table S5<\/a>). For exploratory analysis, these 112 proteins were subjected to Reactome pathway enrichment analysis, which identified neutrophil degranulation as the most significantly enriched pathway (Table\u00a03<\/a>). A total of 19 proteins contributed to this enrichment, including key neutrophil granule proteins such as CEACAM8, PGLYRP1, and RNASE3. Notably, elevated plasma levels of these proteins were observed in COL3A1-low patients (Fig.\u00a03<\/a>).<\/p>\n

Table 3 The top three significantly enriched Reactome pathways.Fig. 3\"Fig.<\/p>\n

Box plots of plasma levels of the 19 proteins involved in the neutrophil degranulation pathway, comparing patients with high COL3A1 expression (patient_high) to those with low COL3A1 expression (patient_low).<\/p>\n

Tissue mRNA levels<\/p>\n

To clarify status of the 11 collagens in local ECM remodelling, microarray gene expression data were analysed to assess mRNA levels in 29 OSCC samples from the oral tongue, 21 clinically normal tissue contralateral to the tumour (NTCT), and 14 healthy controls (HC). Differential gene expression analysis revealed significantly higher mRNA levels of 8 genes (COL1A1, COL3A1, COL4A1, COL5A1, COL6A3, COL15A1, COL18A1, COL24A1) in tumour samples compared to NTCT and HC (FDR\u2009<\u20090.05). No significant differences were seen between NTCT and HC biopsies (Fig.\u00a04<\/a>).<\/p>\n

Fig. 4\"Fig.<\/p>\n

Box-plots showing collagen mRNA levels in healthy controls (HC), clinically normal tongue tissue contralateral to tumour (NTCT) and tumour samples.<\/p>\n

Comparison of tumour collagen levels with clinical parameters<\/p>\n

Since most of the analysed genes showed higher mRNA levels in tumour samples, we next investigated whether these expression differences were associated with age, sex, tumour size, or nodal status. No significant correlations were, however, observed with any of these parameters (data not shown).<\/p>\n

Impact of collagen mRNA levels on survival outcome<\/p>\n

The mRNA levels of the collagen genes were further analysed for their potential association with OS and DFS. Kaplan-Meier log-rank analysis showed that only COL3A1 was significantly correlated with OS (p\u2009=\u20090.048; Fig.\u00a05<\/a>a) and also showed a non-significant trend toward an impact on DFS (p\u2009=\u20090.071; Fig.\u00a05<\/a>b). After adjusting for age, sex, tumour size, and nodal status, Cox proportional hazards regression analysis, however, showed that tumour COL3A1 mRNA levels were not independently associated with overall survival.<\/p>\n

Fig. 5\"Fig.<\/p>\n

Kaplan-Meier plots showing the association of tumour COL3A1 levels with survival. (a) Overall survival; (b) disease-free survival. Patients were stratified into high- and low-groups based on the median COL3A1 level. Survival differences were assessed using the log-rank test.<\/p>\n","protected":false},"excerpt":{"rendered":"Plasma protein levels Among the proteins measured on the Olink Explore 3072 platform, 11 collagen-derived peptides were detected…\n","protected":false},"author":2,"featured_media":769351,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[27314,36537,49,48,7714,273294,30164,227709,1099,1100,32675,273293,66,273295],"class_list":["post-769350","post","type-post","status-publish","format-standard","has-post-thumbnail","category-science","tag-biomarker","tag-biomarkers","tag-ca","tag-canada","tag-cancer","tag-col3a1","tag-collagen","tag-extracellular-matrix","tag-humanities-and-social-sciences","tag-multidisciplinary","tag-oncology","tag-oral-squamous-cell-carcinoma","tag-science","tag-tumour-microenvironment"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/769350","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/comments?post=769350"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/posts\/769350\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media\/769351"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/media?parent=769350"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/categories?post=769350"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ca\/wp-json\/wp\/v2\/tags?post=769350"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}