Background: As there is no consensus on the optimal surgery strategy for multiple primary lung cancer (MPLC), we conducted this study to address this issue by comparing the prognosis of MPLC patients underwent different surgical strategies including sublobar resection and the standard resection through a systemic review and meta-analysis. Methods: Relevant literature was obtained from three databases including PubMed, Embase and Web of Science. Inclusion and exclusion criteria were set for the screening of articles to be selected for further conduction of systemic review and meta-analysis. The HRs of OS of the sublobar group compared with standard resection group were extracted directly or calculated indirectly from included researches. Results: Ten researches published from 2000 to 2017 were included in this study, with 468 and 445 MPLC cases for the standard resection group and sublobar resection group respectively. The result suggested that OS of MPLC patients underwent sublobar resection (segmentectomy or wedge resection for at least one lesion) was comparable with those underwent standard resection approach (lobectomy or pneumonectomy for all lesions), with HR 1.07, 95% CI 0.67–1.71, p = 0.784. Further analysis found no difference in subgroups of synchronous and metachronous (from second metachronous lesion), different population region and dominant sex type. Conclusions: This study may reveal that sublobar resection is acceptable for patients with MPLC at an early stage, because of the equivalent prognosis to the standard resection and better pulmonary function preservation. Further research is needed to validate these findings.

Esophageal squamous cell carcinoma (ESCC) is the major subtype of esophageal cancer with high aggressiveness and poor prognosis. There is an urgent need for understanding the molecular mechanism underlying the development and progression of ESCC. ESCC tissues and corresponding non-neoplastic tissues were collected. The expression and function of miR-124-3p and BCAT1 in two cell lines KYSE-150 and Eca109 were determined. We show downregulation of miR-124-3p expression in ESCC tissues, which is highly correlated with proliferation and migration of ESCC cell lines KYSE-150 and Eca109. miR-124-3p show high correlation with TNM stage and differentiation grade. Furthermore, miR-124-3p directly targets mRNA 3’UTR region of BCAT1, which results in upregulation of BCAT1 expression as observed in ESCC tissues and cell lines. Also, our data indicates that BCAT1 high expression is strongly linked to the disease-free survival, tumor size, pathologic stage, T classification and differentiation grade. On the other hand, we clarified the upstream mechanism regulating miR-124-3p expression in ESCC, which involves in the hypermethylation-silencing regulation mediated by DNA methyltransferase 1(DNMT1), which is of high expression in ESCC tissues and cell lines in the present study. In addition, DNMT1 knockdown or inhibition of DNMT1 function contributes to downregulation of miR-124-3p and BCAT1 expression. Our study thus clarifies a new mechanism that DNMT1/miR-124/BCAT1 axis regulates the development and progression of ESCC.

Mature T-cell and natural killer (NK)-cell lymphomas compose a heterogeneous group of non-Hodgkin lymphomas, and extranodal NK/T-cell lymphoma, nasal type (ENKTL) is an aggressive subtype with sporadic CD30 expression. However, the significance of CD30 expression in ENKTL is controversial. We aimed to classify a large cohort of patients with mature T-cell and NK-cell lymphomas according to the 2016 World Health Organization (WHO) classification guidelines and to study the association between CD30 expression and prognosis of patients with ENKTL. We selected consecutive patients with mature T-cell and NK-cell lymphomas who attended our institution between September 1, 2009 and August 31, 2013. We classified the lymphomas according to the 2016 revision of the WHO classification of lymphoid neoplasms, analyzed the associations between CD30 expression and clinicopathologic features of ENKTL patients, and evaluated the prognostic implications of CD30 expression. We identified 622 consecutive patients with mature T-cell and NK-cell lymphomas, including 317 (51.0%) patients with ENKTL. In addition, CD30 expression was detected in 43 (47.3%) of a subset of 91 patients with ENKTL. No clinicopathologic features were associated with CD30 expression, and CD30 positivity showed no prognostic significance in patients with ENKTL. ENKTL is the most common type of mature T-cell and NK-cell lymphoma diagnosed at our institution. CD30 is frequently expressed in ENKTL and represents a therapeutic target; however, it may not be a prognostic marker.

Neutrophil extracellular traps (NET) have recently emerged as key modulators of cancer progression and metastasis. However, a more comprehensive understanding of the underlying mechanisms could help identify effective strategies to prevent and treat NET-mediated metastasis. In this study, we observed a marked accumulation of intratumoral NETs in metastatic primary lung adenocarcinoma (LUAD). Tumor cells with elevated CXCL2 expression not only recruited neutrophils via interactions with CXCR2 but also facilitated NET formation. In turn, NET-derived DNA (NET-DNA), through specific DNA motifs, directly bound to the extracellular domain of integrin β1 (ITGB1), thereby activating FAK signaling and promoting invasion and metastasis. NET-DNA was capable of enhancing CXCL2 expression through MAPK–ELK1, thereby establishing a positive feedback loop that maintained continuous neutrophil recruitment and NET formation. In both in vitro and in vivo models, targeting either NETs or ITGB1–FAK signaling significantly inhibited LUAD metastasis. These findings suggest that the CXCL2–NET–ITGB1–FAK signaling axis plays a pivotal role in driving NET-mediated metastasis, which provides a rationale for targeting this signaling pathway to inhibit LUAD metastasis. Significance: Tumor-secreted CXCL2 recruits neutrophils and induces formation of neutrophil extracellular traps that bind to integrin β1 to activate FAK signaling and enhance the metastatic potential of lung cancer.

Objective: To investigate the effectiveness of a CTC-based classifier in stratifying stage IB LUAD. Summary of Background Data: Stage IB LUADs have an approximately 70% 5-year survival rate. The clinical application of ACT is controversial due to inconsistent results in a series of trials and few useful guide biomarkers. Thus, there is a pressing need for robust biomarkers to stratify stage IB patients to define which group would most likely benefit from ACT. Methods: Two hundred twelve stage IB LUAD patients were enrolled and were divided into 3 independent cohorts. The aptamer-modified NanoVelcro system was used to enrich the CTCs. Results: A cutoff of 4 CTCs as the optimal prognostic threshold for stage IB LUAD was generated to stratify the patients in a 70-patient cohort into low-risk and high-risk groups. Patients with ≥ 4 CTCs in the training cohort had shorter progression-free survival (P < 0.0001) and overall survival (P < 0.0001) than patients with 4 CTCs can define a high-risk subgroup, providing a new strategy to make optimal clinical decisions for stage IB LUAD.