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MCM8 is a helicase, which participates in DNA replication and tumorigenesis and is upregulated in many human cancers, including lung cancer (LC); however, the function of MCM8 in LC tumour progression is unclear. In this study, we found that MCM8 was expressed at high levels in LC cells and tissues. Further, MCM8 upregulation was associated with advanced tumour grade and lymph node metastasis, and indicated poor prognosis. Silencing of MCM8 suppressed cell growth and migration in vitro and in vivo, while ectopic MCM8 expression promoted cell cycle progression, as well as cell migration, proliferation, and apoptosis. Mechanistically, DNAJC10 was identified as a downstream target of MCM8, using gene array and CO‐IP assays. DNAJC10 overexpression combatted the inhibitory activity of MCM8 knockdown on LC progression, while silencing DNAJC10 alleviated the oncogenic function of MCM8 overexpression. MCM8 expression was positively correlated with that of DNAJC10 in LC samples from The Cancer Genome Atlas database, and DNAJC10 upregulation was also associated with poor overall survival of patients with LC. This study indicated that MCM8/DNAJC10 axis plays an important role in in LC development, and maybe as a new potential therapeutic target or a diagnostic biomarker for treating patients with LC. [ABSTRACT FROM AUTHOR]

Background: Patients with small‐cell lung cancer (SCLC) have a high incidence of synchronous brain metastases (SBM) and a poor prognosis, which causes a heavy burden of morbidity and mortality. A better understanding of the demographic and tumor‐specific characteristics of these patients is critical to guiding clinical practice. The purpose of this study was to investigate the predictive and prognostic value of the clinical characteristics of SCLC patients with SBM at initial diagnosis. Methods: This is a retrospective study based on the data in the latest Surveillance, Epidemiology, and End Results (SEER) version which was released in 2021 for patients diagnosed with SCLC in the presence or absence of SBM from 2010 to 2018. Multivariable logistic regression was performed to identify predictors of the presence of SBM at the initial diagnosis. Kaplan–Meier curves and multivariable Cox regression models were built to compare the prognosis of patients with different clinical characteristics and treatments. Results: A total of 33,169 SCLC patients were enrolled in this study, including 5711 (17.2%) patients with SBM and 27,458 (82.8%) patients without SBM. Patients who are black(HR = 1.313, 95% CI = 1.167–1.478, p < 0.001), higher T stage (T2, HR = 1.193, 95%CI = 1.065–1.348, p = 0.005; T3, HR = 1.169, 95%CI = 1.029–1.327, p = 0.016; T4, HR = 1.259, 95%CI = 1.117–1.418, p < 0.001), lung metastases (HR = 1.434, 95%CI = 1.294–1.588, p < 0.001) and bone metastases (HR = 1.311, 95% CI = 1.205–1.426, p < 0.001) had greater odds of SBM at initial diagnosis. The median overall survival (OS) for SCLC patients with SBM was 5.0 months. Multivariable Cox regression revealed that age ≥ 65 (HR = 1.164, 95% CI = 1.086–1.247, p < 0.025), singled (HR = 1.095, 95% CI = 1.020–1.174, p = 0.012), higher T stage (T3, HR = 1.265, 95% CI = 1.123–1.425, p < 0.001; T4, HR = 1.192, 95% CI = 1.066–1.332, p = 0.002), higher N stage (N2, HR = 1.347, 95%CI = 1.214–1.494, p < 0.001; N3, HR = 1.452, 95%CI = 1.292–1.632, p < 0.001), liver metastases (HR = 1.415, 95%CI = 1.306–1.533, p < 0.001), and bone metastases (adjusted HR = 1.126, 95%CI = 1.039–1.221, p = 0.004). Analysis of treatment regimens showed that patients who received combinational treatment exhibited longer OS than chemotherapy or radiotherapy alone, and surgery combined with chemotherapy and radiotherapy exhibited the longest OS. Conclusions: In this study, we identified risk factors for SBM in SCLC patients and prognostic indicators among this patient population. We also found that patients who received different therapeutic strategies exhibited significant difference on OS, which will provide evidence‐based support for treatment options. [ABSTRACT FROM AUTHOR]

Background: Lymph node (LN) metastasis status is the decision‐making basis for the surgical procedure and adjuvant therapy modalities. Fewer studies have previously focused on LN metastasis in N1 station, especially on peripheral lymph node (PLN) metastasis in N1 station. This study aimed to reveal the metastasis status of PLN of non‐small cell lung cancer (NSCLC), and investigate its effects on N staging. Methods: We retrospectively evaluated a consecutive series of patients who underwent curative resection for histologically confirmed N1 NSCLC. Propensity score matching (PSM) was used to analyze the effects of PLN on N staging. Results: A total of 105 patients with confirmed pathological N1 (pN1) stage NSCLC with solitary nodule and without neoadjuvant therapy were enrolled into the study: 55 patients had intraperipheral LN metastasis (IPLNM), and 50 patients had extra‐peripheral LN metastasis (EPLNM). Before PSM analysis, type of location (P = 0.002), surgical procedure (P = 0.008), number of positive LNs (P = 0.029), number of LNs removed (P = 0.010), lobe of lung cancer (P = 0.031), and vascular invasion (P = 0.049) showed significant differences between the two groups. After PSM analysis, statistically there were differences in type of location (P = 0.034), number of positive LNs (P = 0.008) and vascular invasion (P = 0.049) between them. Conclusion: PLN metastasis was a quite common pattern of LN metastasis in N1 station of NSCLC. IPLNM occurred more frequently in central NSCLC and NSCLC with vascular invasion, and thoracotomy was likely to secure more accurate PLN staging. Clinicians should pay great attention to PLN dissection. Follow‐up data will be needed in order to detect the prognosis of IPLNM patients. [ABSTRACT FROM AUTHOR]