Noninvasive prognostic biomarker potential of quantifying the propeptides of Type XI collagen alpha-1 chain (PRO-C11) in patients with pancreatic ductal adenocarcinoma.

Type XI collagen has been associated with tumor fibrosis and aggressiveness in patients with pancreatic ductal adenocarcinoma (PDAC). The propeptide on Type XI collagen is released into the circulation after proteolytic processing at either amino acid 253 or 511. This allows for a noninvasive biomarker approach to quantify Type XI collagen production. We developed two ELISA-based biomarkers, targeting the two enzymatic cleavage sites (PRO-C11-253 and PRO-C11-511). In a discovery cohort including serum from patients with PDAC (n = 39, Stages 1-4), chronic pancreatitis (CP, n = 12) and healthy controls (n = 20), PRO-C11-511, but not PRO-C11-253, was significantly upregulated in patients with PDAC and CP compared to healthy controls. Furthermore, PRO-C11-511 levels >75th percentile were associated with poor overall survival (OS) (HR, 95% CI: 3.40, 1.48-7.83). The PRO-C11-511 biomarker potential was validated in serum from 686 patients with PDAC. Again, high levels of PRO-C11-511 (>75th percentile) were associated with poor OS (HR, 95% CI: 1.68, 1.40-2.02). Furthermore, PRO-C11-511 remained significant after adjusting for clinical risk factors (HR, 95% CI: 1.50, 1.22-1.86). In conclusion, quantifying serum levels of Type XI collagen with PRO-C11-511 predicts poor OS in patients with PDAC. This supports that Type XI collagen is important for PDAC biology and that PRO-C11-511 has prognostic noninvasive biomarker potential for patients with PDAC.

Multinutrient Supplementation Increases Collagen Synthesis during Early Wound Repair in a Randomized Controlled Trial in Patients with Inguinal Hernia.

BACKGROUND: Inguinal hernia disease is associated with an imbalanced collagen metabolism. Surgical stress has a negative impact on nutrients important for collagen synthesis. OBJECTIVE: We hypothesized that supplementation with a combination of nutrients would enhance collagen biosynthesis in inguinal hernia disease patients when undergoing hernia repair. METHODS: In this exploratory randomized controlled trial, 21 men (age: 55.2 ± 2.8 y; BMI: 25.0 ± 0.7 kg/m2) scheduled for Lichtenstein inguinal hernia repair were assigned to multinutrient supplementation (n = 10; multinutrient group) or no multinutrient supplementation (n = 11; control group). The multinutrient group received 14 g l-arginine, 14 g l-glutamine, 1250 mg vitamin C, and 55 mg zinc daily starting 14 d before surgery and ending 14 d after surgery. The multinutrient and control groups received high-quality protein to ensure a daily intake of 1.5 g protein/kg. Collagen biosynthesis was measured by the biomarkers type I procollagen propeptide (CICP), type III procollagen propeptide (PRO-C3), and type V procollagen propeptide (PRO-C5) in the sera on days -14, 0, and 1, and in the wound fluids on postoperative days 1 and 2. Compliance was recorded after the 28-d intervention period. RESULTS: Serum PRO-C5 concentrations decreased (P < 0.05) postoperatively in the control but not the multinutrient group. Neither CICP nor PRO-C3 serum concentrations differed significantly between the 2 groups. In wound fluid, the CICP concentrations increased (P < 0.05) from days 1 to 2 in the multinutrient group and were 49% higher (P = 0.10) than those in the control group on day 2. Wound fluid concentrations PRO-C3 and PRO-C5 showed no significant time or group differences. The 28-d compliance was similar (P = 0.27) in the 2 groups. CONCLUSION: Oral supplementation with arginine, glutamine, vitamin C, and zinc augment collagen synthesis during the first 2 d after inguinal hernia repair. This trial was registered at clinicaltrials.gov as NCT03221686.

Post-translational modifications of vimentin reflect different pathological processes associated with non-small cell lung cancer and chronic obstructive pulmonary disease.

INTRODUCTION: Vimentin has shown to be highly implicated in cancer initiation and progression. Vimentin is often a target of post-translational modifications (PTMs) which can be disease specific, thus targeting these specific modifications can be of high biomarker potential. In this study we set out to evaluate the biological relevance and serum biomarker potential of citrullinated vimentin (VICM) and non-citrullinated vimentin (VIM) in non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD). METHODS: A competitive ELISA targeting VIM was developed and quantified in serum from patients with NSCLC and COPD. VIM was compared with levels of VICM in the same indications. RESULTS: VIM was significantly increased in NSCLC (n = 100) compared to healthy controls (n = 67) in two independent cohorts (p = 0.0003 and p < 0.0001). Furthermore, VIM was highly increased in late stages of NSCLC (p = 0.001), however VIM was not increased in COPD patients (n = 10). Contrarily, serum levels of VICM was not increased in late stages of NSCLC, but highly elevated in patients with COPD (p < 0.0001). CONCLUSIONS: These findings suggest a biomarker potential of VIM in NSCLC. Our findings also indicate that PTMs of vimentin are highly relevant and that targeting these modifications can have differential biomarker potential.