Psf3 is a member of the evolutionarily conserved heterotetrameric complex GINS (Go-Ichi-Ni-San), which consists of Sld5, Psf1, Psf2, and Psf3. Previous studies have suggested that some GINS complex members are upregulated in cancer, but the status of Psf3 expression in lung adenocarcinoma has not been investigated. The objective of the current study was to determine whether Psf3 plays a role in lung adenocarcinoma by investigating clinical samples. We investigated the status of Psf3 expression in cancer cells of 125 consecutive resected lung adenocarcinomas by immunohistochemistry. Increased Psf3 expression was observed in 27 (21.6%) of the 125 cases. Further, univariate analysis and log-rank test indicated a significant association between Psf3 expression and lower overall survival rate (P = 0.0001 and P < 0.0001, respectively). Multivariate analysis also indicated a statistically significant association between increased Psf3 expression and lower overall survival rate (hazard ratio, 5.2; P = 0.0027). In a subgroup analysis of only stage I patients, increased Psf3 expression was also significantly associated with a lower overall survival rate (P = 0.0008, log-rank test). Moreover, the Ki67 index level was higher in the Psf3-positive group than in the Psf3-low positive group (P < 0.0001, Mann-Whitney U-test). Our results indicated that Psf3 can serve as a prognostic biomarker in lung adenocarcinoma.

Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining.However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.

The GINS complex associates with cell division cycle (Cdc) protein 45 and mini‐chromosome maintenance (Mcm) proteins 2–7 to form the Cdc45–Mcm–GINS (CMG) complex, which is essential for DNA duplication. One member of the GINS complex is Psf3. We previously found that increased Psf3 expression was strongly associated with poor survival in lung adenocarcinoma. Here, we investigated the role of Psf3 expression in non‐small‐cell lung cancer (NSCLC). We verified Psf3 expression in human NSCLC tissues (180 patients) and cell lines. Immunohistochemical analysis revealed that the overexpression of Psf3 was significantly associated with vessel invasion (P = 0.016), lymphatic invasion (P = 0.002), and pleural invasion (P = 0.036). The overall survival rate in patients with Psf3 overexpression was significantly lower than that in patients without Psf3 overexpression (P = 0.006). Multivariate survival analysis revealed Psf3 expression to be an independent risk factor for an unfavorable outcome (P = 0.049). A proximal ligation assay showed interactions between Psf3 and other CMG components (such as Mcm2 and Cdc45) in both NSCLC specimens and cell lines, indicating that Psf3 acted as the CMG complex, which could lead to excessive proliferation. Knockdown of Psf3 inhibited the proliferation of both cell lines by delaying the S phase, which revealed that Psf3 played an important role in cancer proliferation. Thus, Psf3 acted as the CMG complex, promoting excessive proliferation. These results suggest that Psf3 inhibition might be a therapeutic target for NSCLC with Psf3 overexpression.

Sirtuin 1 (Sirt1) is a nicotinamide adenine dinucleotide-dependent class III histone deacetylase. It reportedly can repress cellular apoptosis and senescence to affect DNA repair, stress response and aging. Notably, previous data have indicated that Sirt1 is both a tumor promoter and a tumor suppressor in tumorigenesis. However, Sirt1 expression in primary lung adenocarcinoma remains unknown. Immunohistochemical staining was performed to investigate Sirt1 expression in cancer cells in 125 consecutive resected cases of primary lung adenocarcinoma. Sirt1 expression was found to be increased in 26 (20.8%) of the 125 cases, which correlated significantly with five clinicopathological factors: Ki67 index, hypoxia-inducible factor 1 (HIF1) molecule expression, tumor-node-metastasis (TNM) classification, pulmonary vein invasion and lymphatic duct invasion. In the Sirt1-positive expression group, Sirt1 expression correlated with a higher Ki67 index and higher TNM classification, particularly for lymph node invasion and metastasis, and with a higher number of pulmonary vein invasion and lymphatic duct invasion. Additionally, a negative correlation was identified between HIF1-positive expression and Sirt1-negative expression. These results indicate that Sirt1 overexpression plays a promotional role in tumorigenesis and is closely associated with invasion and metastasis and, thus, it may be associated with prognosis.

The present findings strengthened our previous data demonstrating that high Psf3 expression in primary lung adenocarcinoma plays an important role in disease progression and is a prognostic indicator, particularly in early-stage adenocarcinoma.

The results of our study suggest that segmentectomy may not be recommended for cT1b tumours if pathological invasion is suspected before surgery.

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The histological subtype of non-small-cell lung cancer (NSCLC) is a significant factor when selecting treatment strategies. However, cases are occasionally encountered that are diagnosed as ‘not otherwise specified’ (NOS) prior to surgery, due to an uncertain histological subtype. The present study investigated the prognostic significance of the NOS subtype for patients with resectable NSCLC. Between 2001 and 2011, 1,913 patients were diagnosed with NSCLC using transbronchial biopsy and underwent surgical resection at two facilities in Japan. Of these patients, 151 (7.9%) were pre-operatively diagnosed with NSCLC-NOS (NOS group) and the remainder had confirmed histological subtypes (confirmed group). The present study compared the clinicopathological features and prognoses of these groups. Analyses of resected specimens revealed that pleomorphic cell carcinoma, large cell neuroendocrine cell carcinoma, large cell carcinoma and adenosquamous carcinoma were significantly more common in the NOS group than in the confirmed group (P<0.001, P=0.002, P=0.019 and P=0.014, respectively). The five-year survival rate was significantly poorer in the NOS group (60.5 vs. 67.1%; P=0.010), particularly for stage I disease (70.8 vs. 80.7%; P=0.007). The results of a multivariate analysis of overall survival indicated that NOS was a significant independent prognostic factor (hazard ratio, 1.40; 95% confidence interval, 1.02–1.86; P=0.041). These results indicated that pre-operative NOS was significantly associated with poorer survival, including for stage I disease. In conjunction with other clinicopathological parameters, NOS can be a useful prognostic factor when deciding on a treatment strategy for NSCLC.