Introduction The progression of solid cancers is manifested at the systemic level as molecular changes in the metabolome of body fluids, an emerging source of cancer biomarkers. Methods We analyzed quantitatively the serum metabolite profile using high-resolution mass spectrometry. Metabolic profiles were compared between breast cancer patients (n=112) and two groups of healthy women (from Poland and Norway; n=95 and n=112, respectively) with similar age distributions. Results Despite differences between both cohorts of controls, a set of 43 metabolites and lipids uniformly discriminated against breast cancer patients and healthy women. Moreover, smaller groups of female patients with other types of solid cancers (colorectal, head and neck, and lung cancers) were analyzed, which revealed a set of 42 metabolites and lipids that uniformly differentiated all three cancer types from both cohorts of healthy women. A common part of both sets, which could be called a multi-cancer signature, contained 23 compounds, which included reduced levels of a few amino acids (alanine, aspartate, glutamine, histidine, phenylalanine, and leucine/isoleucine), lysophosphatidylcholines (exemplified by LPC(18:0)), and diglycerides. Interestingly, a reduced concentration of the most abundant cholesteryl ester (CE(18:2)) typical for other cancers was the least significant in the serum of breast cancer patients. Components present in a multi-cancer signature enabled the establishment of a well-performing breast cancer classifier, which predicted cancer with a very high precision in independent groups of women (AUC>0.95). Discussion In conclusion, metabolites critical for discriminating breast cancer patients from controls included components of hypothetical multi-cancer signature, which indicated wider potential applicability of a general serum metabolome cancer biomarker.
Although the role of the thyroid ultrasound is well established in the initial thyroid nodule work up, it is still equivocal whether the thyroid ultrasound pattern could have an impact on refining malignancy risk after an indeterminate cytopathology result. We aim to assess the possible supportive role of the thyroid nodule ultrasound malignancy risk features listed in the Polish guidelines when a biopsy result is indeterminate.We retrospectively reviewed thyroid ultrasound scans from 175 adult patients with thyroid nodules and indeterminate cytopathology results, who underwent thyroid surgery. Sonographic malignancy risk features were reported in accordance with the guidelines of the Polish National Societies Diagnostics and Treatment of Thyroid Carcinoma and included the following: solid structure, hypoechogenicity, microcalcifications, taller than wide shape, irregular margins, features of extrathyroidal expansion, suspicious cervical lymph nodes.The malignancy risk in relevant cytological categories, estimated on the basis of histological verification, was 10.9% for Bethesda III category, 12.1% for Bethesda IV, and 71.4% for Bethesda V. The predominant type of thyroid malignancy was papillary thyroid carcinoma (79%). Thyroid nodules sonographic malignancy risk features provided high specificity but low sensitivity in selected groups of indeterminate thyroid nodules. Microcalcifications was the only characteristic that solely had a clinically relevant positive likelihood ratio (> 10) to suggest malignancy in the analysed cohort, but it was not observed in thyroid nodules eventually verified as follicular thyroid carcinoma. An accumulation of more than one sonographic risk feature yielded significant increase in malignancy risk only in Bethesda V category thyroid nodules.The impact of sonographic malignancy risk features on refining post-biopsy probability of thyroid cancer in thyroid nodule with indeterminate cytopathology, may be inadequate to sort patients (without any doubt) between those who require thyroid surgery and those who only require surveillance. There is an urgent need to search for new tools in the diagnostics of indeterminate thyroid nodules and to standardize thyroid ultrasound reports.
The pain experienced by a patient during a prostate fusion biopsy is cumulative and can also be modulated by many factors. The aim of the study was to assess the association between the degree of pain intensity during prostate biopsy and the region of the biopted organ.The study included a group of 143 patients who underwent prostate fusion biopsy under local analgesia followed by blockage of the periprostatic nerve. After a biopsy, the patients completed the original questionnaire about the pain experienced during the procedure.There was a statistically significant difference in pain score between cores taken in the apex (median 5 (IQR 2-5)), medium level (median 1 (IQR 1-2)), and prostate base (median 1 (IQR 1-3)) (p < 0.001). The malignancy scale ISUP ≥ 2 (p = 0.038) and lower PSA value (r = -0.17; p = 0.046) are associated with higher pain during procedure. Biopsy time was correlated with discomfort (r = 0.19; p = 0.04). Age (p = 0.65), lesion size (p = 0.29), PI-RADS score (p = 0.86), prostate volume (p = 0.22), and the number of cores (p = 0.56) did not correspond to the pain scale.The apex is the most sensitive sector of the prostate. ISUP ≥ 2 and patients with low PSA levels more often indicated higher values on the pain rating scale.
Integrin beta-like 1 (ITGBL1) is a poorly characterized protein comprised of ten EGF-like repeats. Our previous studies suggested that higher ITGBL1 mRNA expression level in the tumor is related with shorter survival of ovarian cancer patients.1 2 Subsequent functional in vitro studies revealed that ITGBL1 overexpression in ovarian cancer cells resulted in the altered adhesion, migration and invasiveness, while it had no effect on proliferation rate and the cell cycle. ITGBL1-overexpressing cells were significantly more resistant to cisplatin and paclitaxel,3 major drugs used in OC treatment.4 In the current study we analyzed gene expression profiles of ITGBL1-overexpressing and control ovarian cancer cells and investigated ITGBL1 influence on ovarian cancer cell signaling pathways.
Methodology
ITGBL1 coding sequence was PCR-amplified from cDNA and cloned into pLNCX2 vector. Retroviral system was used to obtain two ovarian cancer cell lines: OAW42/ITGBL1(+) and SKOV3/ITGBL1(+) with overexpression of ITGBL1. Control cell lines were obtained by transduction with an empty vector. RNA was isolated from wild type, ITGBL1-overexpressing and control cells. DNA microarray experiment was performed using GeneChip™ Human Transcriptome Array 2.0 (Affymetrix, Santa Clara, CA, USA) according to the manufacturer's instructions. Bioinformatical analysis was carried out in R environment (version 3.5.3) with Bioconductor packages.
Results
Using Principal Component Analysis, an unsupervised method of data analysis, we selected gene sets related to major sources of variability in our dataset. Then, by performing Gene Set Enrichment Analysis we found 76 and 146 significantly affected cellular signaling pathways (in OAW42 and SKOV3 cell line, respectively). Majority of them (22 and 44, respectively) were related to extracellular matrix structure and function, integrin signaling, focal adhesion, cell junction, cellular motility, ERBB2 and ERBB4 signaling, etc.
Conclusion
Global gene expression analysis revealed that signaling pathways affected by ITGBL1 overexpression were mostly those related to extracellular matrix organization and function, integrin signaling, focal adhesion, cellular communication and motility. These results are concordant with functional changes observed in ITGBL1-overexpressing cells, like altered adhesiveness, enhanced motility and invasiveness. Overall, our results indicate that higher expression of ITGBL1 in ovarian cancer cells is associated with features that may worsen clinical course of the disease. A.J.Cortez was co-financed by the EU through the European Social Fund (grant-POWR.03.02.00-00-I029).
References
Lisowska, et al. (2014), DOI:10.3389/fonc.2014.00006 Lisowska, et al. (2016), DOI:10.1007/s00432-016-2147-y Cortez, et al. (2020), DOI: 10.3390/cancers12092676 Cortez, et al. (2020), DOI: 10.1007/s00280-017-3501-8
Magnetic resonance imgaing (MRI) targeted biopsy is the gold standard for prostate cancer (PCa) diagnosis. In this study, we examined the association between the operator's experience and the improvement in the precision of the MRI prostate biopsy procedure and the detection of PCa.
