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Introduction: Although histological subtype in lung adenocarcinoma has been reported as a poor prognostic factor in several studies, its utility has not yet been revealed as an adaptation criterion of postoperative adjuvant chemotherapy., Methods: Four hundred ninety-four lung adenocarcinoma patients were enrolled in this retrospective study. A subanalysis was performed in 420 lung adenocarcinoma patients with pathological stage 0-I disease for risk factors of postoperative recurrence., Results: Maximum standardized uptake value (SUVmax) (p < 0.01), pathological stage ≥II (p < 0.04), and adjuvant chemotherapy (p < 0.01) were risk factors for recurrence in the multivariate analysis, whereas histological subtype was not a significant factor for recurrence at all stages. In the subanalysis, univariate analysis showed that carcinoembryonic antigen expression (p < 0.01), prognostic nutrition index (p = 0.03), SUVmax (p < 0.01), lymphatic invasion (p < 0.01), vascular invasion (p < 0.01), grade 3-4 differentiation (p < 0.01), pathological stage ≥IA3 (p < 0.01), and histological subtype (p = 0.03) were significant risk factors of recurrence. SUVmax (p < 0.01) was the only risk factor for recurrence in the multivariate analysis, whereas histological subtype was not (p = 0.07). Relapse-free survival (RFS) was significantly worse in the micropapillary- and solid-predominant subtype groups than in the other subtypes (p = 0.01). On the other hand, RFS with or without uracil-tegafur as adjuvant chemotherapy in lung micropapillary- or solid-predominant adenocarcinoma patients with pathological stage IA-IB disease was not significantly different., Conclusion: This study suggested that histological subtypes, such as micropapillary- or solid-predominant pattern, are risk factors for recurrence in pathological stage 0-I lung adenocarcinoma and may be necessary adjuvant chemotherapy instead of uracil-tegafur., (© 2023 S. Karger AG, Basel.)

Purpose: We aimed to elucidate the functions and clinical relevance of sodium-glucose cotransporter 2 (SGLT2) in resected lung adenocarcinoma., Methods: The protein expression of SGLT2 in tumor samples from 199 patients with lung adenocarcinoma was analyzed by immunohistochemistry, and the protein expression, clinical variables, and survival outcomes were compared., Results: The median SGLT2 expression was significantly higher in advanced-stage and more aggressive adenocarcinomas. Age ≥70 (p < 0.01), BI ≥600 (p < 0.01), PRDX4 <25 (p < 0.01), and SGLT2 ≥12% (p = 0.03) were significant factors for RFS in multivariate analysis. Significant differences were observed in the RFS rates of the groups divided using the cutoff value of SGLT2 ≥12% (5-year RFS: 72.6% vs. 90%) (p < 0.01)., Conclusion: The expression of SGLT2 was more frequently detected in advanced-stage and more aggressive adenocarcinomas with aggressive biological behavior than in their counterparts. The survival analysis revealed that the strong expression of SGLT2 was associated with poorer RFS. The SGLT2 expression predicts postoperative recurrence in lung adenocarcinoma patients., (© 2024 S. Karger AG, Basel.)

Introduction: Although the consolidation diameter of a tumor on computed tomography (CT) is an adaptation criterion for limited resection in early-stage non-small cell lung cancer (NSCLC), whether the maximum standardized uptake value (SUVmax) is also an adaptation criterion for limited resection has not been evaluated., Methods: In total, 478 NSCLC patients with clinical stage IA disease were analyzed, among whom 383 were used to perform a sub-analysis., Results: Multivariate analysis showed that consolidation diameter (odds ratio [OR]: 3.05, p = 0.01), SUVmax (OR: 10.74, p = 0.02), and lymphatic invasion (OR: 10.34, p < 0.01) were risk factors for lymph node metastasis in clinical stage IA NSCLC patients. Furthermore, age (OR: 2.98, p = 0.03), SUVmax (OR: 13.07, p = 0.02), and lymphatic invasion (OR: 5.88, p = 0.02) were risk factors for lymph node metastasis in clinical stage IA lung adenocarcinoma patients according to multivariate analysis., Conclusion: Consolidation diameter of a tumor on CT, SUVmax, and lymphatic invasion are risk factors for lymph node metastasis. However, SUVmax was a risk factor for lymph node metastasis rather than consolidation diameter on CT in lung adenocarcinoma patients. These results suggest that for early-stage lung adenocarcinoma patients, SUVmax is more important for deciding the indication of limited resection than consolidation diameter of the tumor on CT., (© 2023 S. Karger AG, Basel.)

Background: Although T factor is defined as the size of invasive area rather than total tumor size in the eighth edition of the TNM classification, whether the pathological invasive area to tumor ratio (ITR) is a prognostic factor has not yet been evaluated., Methods: In total, 432 lung adenocarcinoma patients were analyzed, among which 266 patients with pathological stage IA were used to perform a subanalysis., Results: Smoking status (odds ratio [OR]: 0.43, p = 0.01), neutrophil-to-lymphocyte ratio (NLR) (OR: 1.97, p = 0.03), maximum standardized uptake value (SUV max ) (OR: 3.62, p < 0.01), and ITR (OR: 6.76, p < 0.01) were significantly different in univariate analysis. Smoking status (OR: 0.34, p < 0.01), SUV max (OR: 3.05, p < 0.01), and ITR (OR: 5.44, p < 0.01) were risk factors for recurrence in multivariate analysis. In patients with pathological stage IA disease, smoking status (OR: 0.34, p = 0.03), NLR (OR: 2.30, p = 0.04), SUV max (OR: 3.63, p < 0.01), pathological invasive area (OR: 4.00, p < 0.01), and ITR (OR: 6.03, p < 0.01) were significantly different in univariate analysis. Smoking status (OR: 0.27, p = 0.02), SUV max (OR: 3.93, p < 0.01), and ITR (OR: 4.38, p < 0.01) were significant risk factors for recurrence in multivariate analysis., Conclusions: SUV max and ITR are risk factors for recurrence. These results suggest that SUV max is important for deciding the indication for limited resection or adjuvant chemotherapy, and ITR is an adaptation criterion for adjuvant chemotherapy for early-stage lung adenocarcinoma patients., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Oxidative stress plays key roles in the progression of lung adenocarcinoma. Recently, we reported that peroxiredoxin 4 (PRDX4), an antioxidant enzyme, can be a prognostic marker of lung adenocarcinoma (LUAD). In the present study, we aimed to further investigate the relationship among the PRDX4 expression, epidermal growth factor receptor (EGFR) mutations and cell proliferation in LUAD. Methods: The expression of PRDX4 was immunohistochemically analyzed and the EGFR mutation status was examined in 127 paraffin-embedded human surgical specimens from patients with stage I LUAD. The PRDX4 expression was considered to be high when >40% of the adenocarcinoma cells were positively stained. In vitro , using plasmid transfection methods, PRDX4 plasmid DNAs were transfected into human lung adenocarcinoma cell lines, A549 (EGFR-wild) or PC-9 (EGFR mutant). The viability of these cells was analyzed using a Cell Counting Kit-8 kit. Results: The number of cases with high PRDX4 expression levels among patients with LUAD with EGFR mutations was significantly larger than that in patients with EGFR wild-type. The combination of the PRDX4 expression level with the EGFR mutation status was closely associated with the prognosis of patients with stage I LUAD. Viability assays showed that the proliferation of A549 cells was significantly suppressed after PRDX4 plasmid transfection, while the overexpression of PRDX4 had no effect on the proliferation of EGFR-mutant PC-9 cells. Conclusions: The PRDX4 expression and EGFR mutation status were significantly associated with the prognosis of patients with stage I LUAD, and EGFR mutations affected the role of PRDX4 in the proliferation of LUAD cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Oxidative stress plays pivotal roles in the progression of lung adenocarcinoma (LUAD) through cell signaling related closely to cancer growth. We previously reported that peroxiredoxin 4 (PRDX4), a secretory-type antioxidant enzyme, can protect against the development of various diseases, including potential malignancies. Since many patients with early-stage LUAD develop recurrence, even after curative complete resection, we investigated the association of the PRDX4 expression with the clinicopathological features and recurrence/prognosis using post-surgical samples of stage I-LUAD. Methods: The expression of PRDX4 and MIB-1, a widely accepted Ki67 protein, was immunohistochemically analysed in 206 paraffin-embedded tumour specimens of patients with stage I-LUAD. The PRDX4 expression was considered to be weak when less than 25% of the adenocarcinoma cells showed positive staining. Results: A weak PRDX4+ expression demonstrated a significantly close relationship with pathologically poor differentiation, highly invasive characteristics and recurrence. The decrease in PRDX4-positivity potentially induced cell growth in LUAD, which was correlated significantly with a very high MIB-1 labelling index (≥17.3%). Univariate/multivariate analyses revealed that the subjects with both weak PRDX4+ expression and a very high MIB-1 index had significantly worse disease-free survival rates than other subjects. Conclusions: The combination of weak PRDX4 expression and a very high MIB-1 index can predict high proliferating activity and recurrence with a potential poor prognosis, especially in post-operative stage I-LUAD patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.