Human pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. Changes in O-glycosylation affect posttranslationally modified O-GalNAc proteins resulting in profound cellular alterations. Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties. Forced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data. Tn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037). This study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker.

Background: Mitochondria are suggested to be important organelles for cancer initiation and promotion. This study was designed to evaluate the prognostic value of MTC02, a marker for mitochondrial content, in prostate cancer. Methods: Immunohistochemistry of using an antibody against MTC02 was performed on a tissue microarray (TMA) containing 11,152 prostate cancer specimens. Results were compared to histological phenotype, biochemical recurrence, ERG status and other genomic deletions by using our TMA attached molecular information. Results: Tumor cells showed stronger MTC02 expression than normal prostate epithelium. MTC02 immunostaining was found in 96.5% of 8,412 analyzable prostate cancers, including 15.4% tumors with weak, 34.6% with moderate, and 46.5% with strong expression. MTC02 expression was associated with advanced pathological tumor stage, high Gleason score, nodal metastases (p < 0.0001 each), positive surgical margins (p = 0.0005), and early PSA recurrence (p < 0.0001) if all cancers were jointly analyzed. Tumors harboring ERG fusion showed higher expression levels than those without (p < 0.0001). In ERG negative prostate cancers, strong MTC02 immunostaining was linked to deletions of PTEN, 6q15, 5q21, and early biochemical recurrence (p < 0.0001 each). Moreover, multiple scenarios of multivariate analyses suggested an independent association of MTC02 with prognosis in preoperative settings. Conclusions: Our study demonstrates high-level MTC02 expression in ERG negative prostate cancers harboring deletions of PTEN, 6q15, and 5q21. Additionally, increased MTC02 expression is a strong predictor of poor clinical outcome in ERG negative cancers, highlighting a potentially important role of elevated mitochondrial content for prostate cancer cell biology.

Objectives: The aim was to investigate the prevalence of probable depression and probable anxiety and to investigate the determinants of depressive symptoms and anxiety symptoms among transgender people. Methods: In this “Transgender Survey” (n = 104) we included transgender people who had joined self-help groups to obtain and share information about the gender-affirming surgeries performed at the Division of Plastic, Reconstructive and Aesthetic Surgery at the University Medical Center Hamburg-Eppendorf. Data collection took place between April and October 2022. To measure probable depression, the patient health questionnaire-9 was used. The generalized anxiety disorder-7 was used to quantify probable anxiety. Results: The prevalence of probable depression was 33.3% and it was 29.6% for probable anxiety. Multiple linear regressions showed that both more depressive symptoms and anxiety symptoms were significantly associated with younger age (β = −0.16, p < 0.01; β = −0.14, p < 0.01), being unemployed (e.g., full-time employed compared to unemployment: β = −3.05, p < 0.05; β = −2.69, p < 0.05), worse self-rated health (β = −3.31, p < 0.001; β = −1.88, p < 0.05), and having at least one chronic disease (β = 3.71, p < 0.01; β = 2.61, p < 0.05). Conclusions: Remarkably high prevalence rates were identified among transgender people. Furthermore, risk factors of poor mental health (e.g., unemployment or younger age) were identified—which can help to address transgender people at risk for poor mental health.

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been suggested to play a role in cancer. To assess its role in prostate cancer, LPCAT1 expression was analyzed on a tissue microarray containing samples from 11,152 prostate cancer patients. In benign prostate glands, LPCAT1 immunostaining was absent or weak. In prostate cancer, LPCAT1 positivity was found in 73.8% of 8786 interpretable tumors including 29.2% with strong expression. Increased LPCAT1 expression was associated with advanced tumor stage (pT3b/T4) (p < 0.0001), high Gleason score (≥4 + 4) (p < 0.0001), positive nodal involvement (p = 0.0002), positive surgical margin (p = 0.0005), and early PSA recurrence (p < 0.0001). High LPCAT1 expression was strongly linked to ERG‐fusion type prostate cancer. Strong LPCAT1 staining was detected in 45.3% of ERG positive but in only 16.7% of ERG negative tumors (p < 0.0001). Within ERG negative cancers, LPCAT1 staining was strongly increased within the subgroup of PTEN deleted cancers (p < 0.0001). Further subgroup analyses revealed that associations of high LPCAT1 expression with PSA recurrence and unfavorable tumor phenotype were largely driven by ERG negative cancers (p < 0.0001) while these effects were substantially mitigated in ERG positive cancers (p = 0.0073). The prognostic impact of LPCAT1 expression was independent of histological and clinical parameters. It is concluded, that LPCAT1 measurement, either alone or in combination, may be utilized for better clinical decision‐making. These data also highlight the potentially important role of lipid metabolism in prostate cancer biology.

Here, we report the prevalence of loneliness and social isolation and investigate the levels of loneliness and social isolation among transgender and gender diverse people using cross-sectional data from the HH-TPCHIGV study. Using the De Jong Gierveld tool, we assess loneliness, using the Bude and Lantermann tool, we assess perceived social isolation and using the Lubben Social Network Scale, we assess objective social isolation. The prevalence rate of loneliness was 83.3% (perceived social isolation: 77.7%; objective social isolation: 34.4%). Regressions revealed that favorable outcomes (i.e., lower loneliness levels, lower perceived social isolation, and lower objective social isolation) were consistently associated with higher school education. Beyond that, we identify an association between particularly poor health-related factors and higher loneliness and objective social isolation levels. We also report that unemployment was significantly associated with higher levels of perceived social isolation. In conclusion, we show high prevalence rates of loneliness and social isolation among transgender and gender diverse people. Additionally, important correlates (e.g., education, health-related factors, or unemployment) were identified. Such knowledge may provide help to address transgender and gender diverse people at risk for loneliness and social isolation.