RESUMO
In esophageal adenocarcinoma, the presence of lymph node metastases predicts patients' survival even after curative resection. Currently, there is no highly accurate marker for detecting the presence of lymph node metastasis. The SEMA3F/NRP2 axis was initially characterized in axon guidance and recent evidence has revealed its significant involvement in lymphangiogenesis, angiogenesis, and carcinogenesis. Hence, the objective of this study was to elucidate the roles of SEMA3F and its receptor NRP2 in esophageal adenocarcinoma. We conducted an immunohistochemical evaluation of SEMA3F and NRP2 protein expression in 776 patients with esophageal adenocarcinoma who underwent Ivor-Lewis esophagectomy at the University Hospital of Cologne. Total and positive cancer cell counts were digitally analyzed using QuPath and verified by experienced pathologists to ensure accuracy. Positive expression was determined as a cell percentage exceeding the 50th percentile threshold. In our cohort, patients exhibiting SEMA3F positive expression experience significantly lower pT- and pN-stages. In contrast, positive NRP2 expression is associated with the presence of lymph node metastases. Survival analyses showed that the expression status of NRP2 had no impact on patient survival. However, SEMA3F positivity was associated with a favorable patient survival outcome (median OS: 38.9 vs. 26.5 months). Furthermore, SEMA3F could be confirmed as an independent factor for better patient survival in patients with early tumor stage (pT1N0-3: HR = 0.505, p = 0.014, pT1-4N0: HR = 0.664, p = 0.024, pT1N0: HR = 0.483, p = 0.040). In summary, SEMA3F emerges as an independent predictor for a favorable prognosis in patients with early-stage esophageal adenocarcinoma. Additionally, NRP2 expression is linked to a higher risk of lymph node metastases occurrence. We hypothesize that low SEMA3F expression could identify patients with early-stage tumors who might benefit from more aggressive treatment options or intensified follow-up. Furthermore, SEMA3F and its associated pathways should be explored as potential tumor-suppressing agents.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Metástase Linfática , Proteínas de Membrana , Proteínas do Tecido Nervoso , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Esofagectomia , Proteínas de Membrana/metabolismo , Estadiamento de Neoplasias , Proteínas do Tecido Nervoso/metabolismo , Neuropilina-2/metabolismo , Neuropilina-2/genética , PrognósticoRESUMO
OBJECTIVE: This cross-sectional pilot study evaluated the impact of age on masticatory performance among individuals aged 65 to 106 years, as part of the Heidelberg Dental Centenarian Study (HD-100Z) conducted in South-Western Germany. MATERIALS AND METHODS: A total of 31 centenarians were recruited, alongside 31 individuals each from the age groups 75-99 and 65-74, matched based on sex, prosthetic status, and number of teeth. Masticatory performance was assessed using a two-colored chewing gum test and digital image processing. Multiple linear regression analysis was performed to assess the effect of age, sex, number of teeth, type of prosthesis on the masticatory performance. RESULTS: Masticatory performance, as measured by the standard deviation of hue in the chewing gum test, decreased significantly in centenarians compared to individuals aged 75-99 years (-0.112, p = 0.037) and those aged 65-74 years (-0.274, p < 0.001). The effects of sex, number of teeth, and type of prosthesis on masticatory performance were not significant associations (p ≥ 0.135). CONCLUSION: The findings suggest that age may have a significant influence on masticatory performance in the studied age groups, challenging previous notions that aging itself has little impact on masticatory ability. The inclusion of centenarians in the study highlights the need for further investigation into masticatory function in age groups reaching up to 100 years or more. CLINICAL RELEVANCE: This study contributes to the understanding of how ageing affects oral function, which may guide dental treatment approaches for older individuals, and set the stage for more in-depth investigations in this field in the future.