Background: Pulmonary embolism (PE) is the third most common cause of death for cardiovascular diseases in Europe. Quick PE diagnosis is therefore crucial for prognosis improvement. It is critical to have suitable screening tests both to exclude PE as well to select patient with highest likelihood of PE occurrence. Currently D-dimer test is accepted as important tool useful to exclude PE in low risk patients. Our goal was to assess the D-dimer test positive prognostic value. Methods: A retrospective study based on medical record analysis of consecutively admitted patients to 9 wards of The University Clinical Center in Katowice who were hospitalized during four consecutive years was performed. Three hundred and seventy patients met the inclusion criteria for the study, which involved the D-dimer tests and computed tomographic pulmonary angiography (CTPA) performed during hospitalization. Assessed patients were divided into two groups: PE confirmed and PE excluded by CTPA. Results: We have found that patients with D-dimer levels higher than 2,152 ng/mL had significantly increased risk of PE [area under curve (AUC) of 0.69; 95% CI, 0.64–0.75; P65 years of age had D-dimer cut-off point moved to the level of 2,652 ng/mL (AUC of 0.67; 95% CI, 0.52–0.81; P<0.05). Conclusions: Whereas the NPV of the D-dimer test is generally accepted our results suggest that, in selected cases, an increased plasmatic D-dimer levels may have PPV in PE diagnosis. Patients with the history of neoplasm have higher cut-off D-dimer points above which we should consider increased PE likelihood. CTPA should be considered even for patients with low probability of PE when D-dimer values exceed four times the normal level.

ADAM10 and ADAM17 have a role in inflammation and diseases associated with inflammation, such as diabetes, cardiovascular diseases (CVD) or cancer, e.g., colorectal cancer (CRC). The aim of this study was to evaluate whether ADAM10 and ADAM17 could be biomarkers of CRC. To achieve this goal, CRC tumors and a surgical margin from 72 patients with CRC were collected. The concentration of ADAM proteins was measured by the ELISA method. Results were analyzed statistically and compared with selected clinical parameters. We found that ADAM17 protein concentration in the tumor samples was higher in patients with diabetes mellitus type 2 (DMT2) (0.28 vs. 0.2 ng/µg protein; p = 0.01) and in the surgical margin was higher both in patients with coexisting DMT2 (0.22 vs. 0.16 ng/µg protein; p < 0.05) and CVD (0.21 vs. 0.13 ng/µg protein; p < 0.01). The concentration of ADAM10 was higher in the surgical margin than in the tumor (249.34 vs. 228.82 pg/µg protein), and the concentration of ADAM17 was higher in the tumor than in the margin (0.23 vs. 0.18 ng/µg protein), but results were not statistically significant. In conclusion, the results of our study indicate that ADAM10 and ADAM17 may be potential biomarkers in cancer linked with DMT2 and CVD as diseases associated with inflammation.

Gastrointestinal (GI) cancers are some of the most common cancers in the world and their number is increasing. Their etiology and pathogenesis are still unclear. ADAM proteins are a family of transmembrane and secreted metalloproteinases that play a role in cancerogenesis, metastasis and neoangiogenesis. MicroRNAs are small single-stranded non-coding RNAs that take part in the post-transcriptional regulation of gene expression. Some ADAM proteins can be targets for microRNAs. In this review, we analyze the impact of microRNA/ADAM protein axes in GI cancers.

Chronic inflammation is a confirmed risk factor for colorectal cancer (CRC). Indicators of systemic inflammatory response (SIR), such as neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), are easily accessible indicators of the generalized inflammatory response. At the molecular level, inflammation-related carcinogenesis involves proteins from the adamalysin family: ADAM10 and ADAM17. The aim of the study was to assess NLR and PLR and their relationship with selected clinical parameters in CRC patients, as well as the correlation between ADAM10 and ADAM17 in tumor tissue and matched surgical margins with NLR and PLR values. Tumor tissue material matched surgical margins, and blood was collected from 66 patients who underwent surgery because of CRC. The concentrations of ADAM10 and ADAM17 in the collected material were tested using the enzyme-linked immunosorbent assay (ELISA) method. SIR parameters (NLR, PLR) were also determined. The results were statistically analyzed and compared with selected clinical parameters. Results: The study showed that PLR was lower in patients with comorbid cardiovascular diseases (CVD). In patients who underwent preoperative treatment, both the NLR and PLR values were higher than in patients who underwent primary surgery. There was also a negative correlation between ADAM17 concentrations in the surgical margin and PLR values. In conclusion, the presence of additional diseases such as CVD or diabetes mellitus type 2 (DMT2) or the use of preoperative treatment should be taken into account when assessing SIR parameters in CRC patients. Moreover, no clear correlations have been found between ADAM10 and ADAM17 and SIR parameters.

Abstrakt: Nowotwory złośliwe przewodu pokarmowego zajmują czołowe miejsce zarówno wśród przyczyn zachorowań jak i zgonów z powodu chorób nowotworowych na świecie. Wciąż poszukuje się potencjalnych biomarkerów, które mogłyby posłużyć jako czynniki predykcyjne i prognostyczne w tych nowotworach. Wśród białek, które mogłyby pełnić taką rolę, wymienia się adamalizyny. Liczne białka z tej rodziny są zaangażowane w wielu etapach nowotworzenia, od procesu różnicowania się pojedynczych komórek, wzrost i progresję guza do tworzenia przerzutów odległych. Dzieje się to m.in. poprzez ścieżki sygnałowe związane z aktywacją insulinopodobnych czynników wzrostu, naskórkowych czynników wzrostu czy oddziaływanie na czynnik martwicy nowotworu TNF-α. Szczególnie istotna w wyjaśnieniu patomechanizmu rozwoju raków gruczołowych przewodu pokarmowego wydaje się ścieżka sygnałowa związana z aktywacją cytokin prozapalnych. Przewlekły stan zapalny jest bowiem dobrze udokumentowanym czynnikiem ryzyka rozwoju tej grupy chorób nowotworowych. Poznanie roli białek z rodziny adamalizyn w rozwoju i patogenezie nowotworów złośliwych przewodu pokarmowego wymaga wciąż dalszych badań. W artykule podjęto próbę syntezy aktualnej wiedzy na temat wykorzystania wybranych białek z rodziny adamalizyn jako biomarkerów nowotworów złośliwych przewodu pokarmowego.

The role of adamalysins (ADAMs) has been widely described in many processes related to carcinogenesis, angiogenesis, inflammation, metastasis, and metabolic disorders. Despite numerous studies, their role in colorectal cancer (CRC) remains unclear. The aim of this study was to evaluate the expression of selected ADAM genes in colorectal cancer tissue and corresponding surgical margins. In addition, for a subgroup of patients, the expression of selected proteins from the ADAM family was assessed. The final study group consisted of 67 patients who underwent elective surgery for colorectal cancer. The relative expression of the ADAM10, 12, 17, and 28 genes was expressed as relative quantification (RQ) and determined by real-time quantitative PCR (RT-qPCR) in tumor tissue and surgical margins. In addition, for a subgroup of 45 patients, the expression of ADAM10, 12, and 17 proteins was assessed by ELISA. Associations between ADAM expression and clinicopathological parameters were analyzed statistically. ADAM12 gene expression was significantly higher in tumor than in margin tissue (median RQ: 0.995 vs. 0.251; p = 0.003), whereas ADAM28 RQ was significantly higher in the margin (median RQ: 0.400 vs. 0.204; p = 0.021). No significant differences were observed in the expression of the ADAM10, ADAM12, ADAM17, or ADAM28 genes based on tumor stage, sex, substance use, BMI, or age, except for nominally higher ADAM12 gene expression in patients over 65 years of age (p = 0.033). Among patients under 65 years of age with cardiovascular disease (CVD), ADAM28 RQ in tumor tissue was significantly higher than in those without CVD (p < 0.05). In obese patients with CVD, a markedly increased expression of ADAM28 in tumor tissue was observed, regardless of age (1.469 vs. 0.132; p < 0.005). Significant positive correlations were observed between the ADAM10 and ADAM17 RQ, and between the ADAM10 and ADAM28 RQ, in both tumor and marginal tissues (all adjusted p < 0.01). No significant correlations were found between gene expression and corresponding protein levels for ADAM10, ADAM12, or ADAM17. ADAM10, 12, 17, and 28 are poor biomarkers for colorectal cancer, but their significance may increase in patients with comorbid metabolic disorders. The lack of correlation between protein expression and gene expression suggests the contribution of post-transcriptional and post-translational regulatory mechanisms, which justifies further research.