BACKGROUND: Several cathepsins have been identified as being involved in the development of cancer. Nevertheless, the connection between cathepsins and skin cancers remained highly elusive.
METHODS: A bidirectional Mendelian randomization (MR) analysis was performed to investigate the causal association between cathepsins and skin malignancies. The genome-wide association studies (GWAS) data for cathepsins, malignant melanoma (MM), and basal cell carcinoma (BCC) were obtained from European research. The primary method employed was inverse variance weighted. In addition, MR-Egger, weighted median, weighted mode, and simple mode were also executed. Sensitivity analysis was performed using Cochran\'s Q test, MR-Egger, and MR-PRESSO.
RESULTS: From univariable MR (UVMR), cathepsin H, and S were determined to have a causal relationship with BCC. Additionally, cathepsin H was identified as associated with MM. Multivariable MR (MVMR) showed that after correcting for risk factors of skin carcinoma, cathepsin H was detected to be protective against BCC, whereas cathepsin S has been observed as a risk factor for BCC. No substantial pleiotropy and heterogeneity were identified in the sensitivity analysis.
CONCLUSIONS: This study was the first to establish a direct link between cathepsins and skin malignancies. Cathepsin H and S have the potential to serve as new biomarkers for BCC, offering valuable assistance in the prompt identification, treatment, and prevention of the disease. Nevertheless, additional clinical trials are required to validate our findings.

UNASSIGNED: Circulating metabolites, which play a crucial role in our health, have been reported to be disordered in basal cell carcinoma (BCC). Despite these findings, evidence is still lacking to determine whether these metabolites directly promote or prevent BCC\'s progression. Therefore, our study aims to examine the potential effects of circulating metabolites on BCC progression.
UNASSIGNED: We conducted a two-sample Mendelian randomization (MR) analysis using data from two separate genome-wide association studies (GWAS). The primary study included data for 123 blood metabolites from a GWAS with 25,000 Finnish individuals, while the secondary study had data for 249 blood metabolites from a GWAS with 114,000 UK Biobank participants.GWAS data for BCC were obtained from the UK Biobank for the primary analysis and the FinnGen consortium for the secondary analysis. Sensitivity analyses were performed to assess heterogeneity and pleiotropy.
UNASSIGNED: In the primary analysis, significant causal relationships were found between six metabolic traits and BCC with the inverse variance weighted (IVW) method after multiple testing [P < 4 × 10-4 (0.05/123)]. Four metabolic traits were discovered to be significantly linked with BCC in the secondary analysis, with a significance level of P < 2 × 10-4 (0.05/249). We found that all the significant traits are linked to Polyunsaturated Fatty Acids (PUFAs) and their degree of unsaturation.
UNASSIGNED: Our research has revealed a direct link between the susceptibility of BCC and Polyunsaturated Fatty Acids and their degree of unsaturation. This discovery implies screening and prevention of BCC.

OBJECTIVE: Basal and squamous cell carcinoma (BCC, SCC), collectively referred to as keratinocyte-derived skin cancer (KC), are the most common human cancers worldwide. Surgery is the treatment of choice, but may represent overtreatment in the very elderly. This study aims to address this issue by investigating the life expectancy of patients over 80 years after surgery.
METHODS: A single-center, retrospective study was performed to include surgically treated KC patients at the Department of Dermatology and Venereology of the University Hospital in St. Pölten, Austria, between 01.01.2011 and 31.12.2017, who were 80 years or older. Data on individual survival (cut-off April 30, 2020), date and cause of death were retrieved from the Austrian national demographic database at Statistics Austria (Vienna).
RESULTS: 940 patients (450 female, 490 male, 639 BCCs, 301 SCCs) were included with 307 being alive at the cut-off date. Median postoperative survival was 57 months (95% CI, 54-63 months).
CONCLUSIONS: With a median postoperative survival of almost 5 years, surgery remains a valid treatment option for KC at the end of life. However, 77 of the treated patients died within a year after surgery and preoperative assessment might have helped to avoid overtreatment in some of these cases.

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BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy. BCCs occur mainly in exposed areas, such as the face and scalp. Therefore, surgical resection with narrow margins is highly desirable. However, narrow margins may increase the risk of positive histopathological margins. Outcomes for such treatment might be unfavorable, but evidence for such a conclusion is lacking.
METHODS: Between April 2015 and November 2023, a total of 230 Japanese cases with BCC which underwent surgical resection with 2-mm, 3-mm, or 5-mm margins were followed in our hospital. We conducted a retrospective review that focused on the recurrence rate and histopathological margins.
RESULTS: Recurrence was recorded if the follow-up time was longer than 3 months. One of the 198 cases (0.5%) developed a recurrence. The mean lateral and deep histopathological margins were 2,525.4 μm (30.8-14,034.6 μm) and 3,409 μm (199.9-16,523.6 μm), respectively. Recurrence rate was associated with tumor size and clinical tumor border. However, histopathological margin was not associated with recurrence rate, even when it was less than 1,000 μm.
CONCLUSIONS: A narrow histopathological margin is acceptable for surgical resection of BCC in Japanese patients.

BACKGROUND: Actinic keratoses (AKs) are rough, scaly patches from UV exposure, increasing the risk of non-melanoma skin cancer (NMSC). This study examines AK incidence in Korea and its role as a risk factor for NMSC.
METHODS: A retrospective nationwide register-based cohort study analyzed 2,917 AK patients and 14,585 controls from 2002 to 2019. Patients diagnosed with AK were followed until NMSC occurrence, death, emigration, or December 2019.
RESULTS: AK incidence reached 44.8 per 100,000 person-years in 2019. The adjusted hazard ratio for NMSC in AK patients was 8.91 (95% confidence interval, 5.72-13.90). Higher NMSC risk was observed in female AK patients, those under 60 years, and those with lower income levels. The 16-year cumulative incidence of NMSC was 4.19% in AK patients versus 0.44% in controls.
CONCLUSIONS: AK significantly increases the risk of NMSC in Koreans, highlighting the need for tailored surveillance and treatment strategies.

OBJECTIVE: Research has previously established connections between the intestinal microbiome and the progression of some cancers. However, there is a noticeable gap in the literature in regard to using Mendelian randomisation (MR) to delve into potential causal relationships between the gut microbiota (GM) and basal cell carcinoma (BCC). Therefore, the purpose of our study was to use MR to explore the causal relationship between four kinds of GM (Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae) and BCC.
METHODS: We used genome-wide association study (GWAS) data and MR to explore the causal relationship between four kinds of GM and BCC. This study primarily employed the random effect inverse variance weighted (IVW) model for analysis, as complemented by additional methods including the simple mode, weighted median, weighted mode and MR‒Egger methods. We used heterogeneity and horizontal multiplicity to judge the reliability of each analysis. MR-PRESSO was mainly used to detect and correct outliers.
RESULTS: The random-effects IVW results showed that Bacteroides (OR = 0.936, 95% CI = 0.787-1.113, p = 0.455), Streptococcus (OR = 0.974, 95% CI = 0.875-1.083, p = 0.629), Proteobacteria (OR = 1.113, 95% CI = 0.977-1.267, p = 0.106) and Lachnospiraceae (OR = 1.027, 95% CI = 0.899-1.173, p = 0.688) had no genetic causal relationship with BCC. All analyses revealed no horizontal pleiotropy, heterogeneity or outliers.
CONCLUSIONS: We found that Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae do not increase the incidence of BCC at the genetic level, which provides new insight for the study of GM and BCC.

Facial basal cell carcinoma (BCC) surgery enhances the quality of life (QoL) but leaves patients with inferior QoL, presumably caused by scarring, emphasizing the need to understand post-surgery aesthetic satisfaction. This study aimed to validate the Lithuanian version of the Patient and Observer Scar Assessment Scale (POSAS) 2.0 and utilise it to identify scar evaluation differences and correlations among POSAS scores and specific aesthetic facial regions, age, gender, surgery types, and short- and long-term QoL. Employing a prospective longitudinal design, 100 patients with facial scars after surgical BCC removal were enrolled. The validation phase confirmed the translated POSAS 2.0 psychometric properties, while the pilot phase used statistical analyses to compare scores among demographic and clinical groups and evaluate correlations between scar assessment and QoL. The findings indicate that the translated Lithuanian version of POSAS 2.0 exhibits good psychometric properties, revealing insights into aesthetic satisfaction with post-surgical facial scars and their impact on QoL. The Lithuanian version of the POSAS 2.0 was established as a valid instrument for measuring post-surgical linear scars. QoL with scar assessment statistically significantly correlates, 6 months after surgery, with worse scores, particularly notable among women, younger patients, and those with tumours in the cheek region.

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30). CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS. Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.

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