The Prognostic Value of Preoperative Serum Tumor Markers in Non-Small Cell Lung Cancer Varies With Radiological Features and Histological Types

ObjectivesTo assess the association between common-used serum tumor markers and recurrence of lung adenocarcinoma and squamous cell carcinoma separately and determine the prognostic value of serum tumor markers in lung adenocarcinoma featured as ground glass opacities.MethodsA total of 2,654 non-small cell lung cancer patients undergoing surgical resection between January 2008 and September 2014 were analyzed. The serum levels of carcinoma embryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153) and carbohydrate antigen 199 (CA199) were tested preoperatively. Survival analyses were performed with COX proportional hazard regression.ResultsAmong patients with lung adenocarcinoma, elevated preoperative serum CEA(HR=1.246, 95%CI:1.043-1.488, P=0.015), CYFRA21-1(HR=1.209, 95%CI:1.015-1.441, P=0.034) and CA125(HR=1.361, 95%CI:1.053-1.757, P=0.018) were significantly associated with poorer recurrence free survival (RFS). Elevated preoperative serum CA199 predicted worse RFS in patients diagnosed with lung squamous cell carcinoma (HR=1.833, 95%CI: 1.216-2.762, P=0.004). Preoperative serum CYFRA21-1(HR=1.256, 95%CI:1.044-1.512, P=0.016) and CA125(HR=1.373, 95%CI: 1.050-1.795, P=0.020) were independent prognostic factors for patients with adenocarcinoma presenting as solid nodules while serum CEA (HR=2.160,95%CI:1.311-3.558, P=0.003) and CA125(HR=2.475,95%CI:1.163-5.266, P=0.019) were independent prognostic factors for patients with adenocarcinoma featured as ground glass opacities.ConclusionsThe prognostic significances of preoperative serum tumor markers in non-small cell lung cancer were associated with radiological features and histological types

Segmentectomy for ground glass-dominant invasive lung cancer with tumour diameter of 2–3 cm: protocol for a single-arm, multicentre, phase III trial (ECTOP1012)

Introduction Previous studies demonstrated that wedge resection is sufficient for ground glass-dominant lung adenocarcinoma (LUAD) with tumour diameter ≤2 cm, however, the optimal surgical type for ground glass-dominant LUAD with tumour diameter of 2–3 cm remains unclear. The purpose of this trial is to investigate the safety and efficacy of segmentectomy for ground glass-dominant invasive LUAD with tumour size of 2–3 cm.Methods and analysis We initiated a phase III trial to investigate whether segmentectomy is suitable for ground glass-dominant invasive LUAD with tumour size of 2–3 cm. This trial plans to enrol 307 patients from multiple institutions including four general hospitals and two specialty cancer hospitals over a period of 5 years. The primary endpoint is 5 year disease-free survival. Secondary endpoints are lung function, 5 year overall survival, the site of tumour recurrence and metastasis, segmentectomy completion rate, radical segmentectomy (R0 resection) completion rate and surgery-related complications.Ethics and dissemination This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Centre (reference 2212267-18) and by the institutional review boards of each participating centre. Written informed consent is required from all participants. The study results will be published in a peer-reviewed international journal.Trial registration number NCT05717803

Additional file 1 of Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer

Additional file 1: Figure S1. Sankey diagram (A) and details (B) of PD-L1 expression using 22C3 assays in two multi-focal primary tumors. TPS: tumor proportion score

An androgen reduced transcript of LncRNA GAS5 promoted prostate cancer proliferation

<div><p>Prostate cancer (PCa) becomes a leading cause of death in males nowadays. Recent reports showed that androgen-responsive long non-coding RNAs played important roles in tumorigenesis and progression of PCa. In this study, we focused on a special transcript of GAS5 (ENST00000456293.5, GAS5-007), which was reported as a tumor suppressor. Here, we demonstrated GAS5-007 was reduced by androgen treatment and inhibited by AR. Next, we explored the expression level of GAS, finding the expression of it in PCa tissue was higher than normal tissue in both public databases and human tissue samples. Functional analysis of GAS5 showed it was related to regulating translational elongation, protein biosynthesis, and transcription. Moreover, we observed GAS5-007 knockdown inhibited the proliferation, cell cycle and promoted cell apoptosis of PCa. We also constructed a GAS5-miRNA network to explain the different roles of different GAS5 transcripts in PCa. This study provides novel insights to identify potential diagnostic biomarker and therapy target for prostate cancer in clinical treatment.</p></div

GO biological process and KEGG pathway enrichment analysis of LncRNA GAS5.

<p>(A) Gene co-expression networks of GAS5 were constructed according to Pearson correlation coefficients. (B) GO biological process analysis of GAS5-positive genes and GAS5-negative genes (E). (C) KEGG pathway enrichment analysis of GAS5-positive genes and GAS5-negative genes (F) using MAS 3.0. (D) The PPI network.</p

Differences of targeted miRNA of GAS5-001, GAS5-002 and GAS-007.

<p>(A) Intersections of GAS5-001, GAS5-002 and GAS5-007 targeted miRNA. (B) Targeted miRNA networks of GAS5-001, GAS5-002 and GAS5-007.</p

LncRNA GAS5 promoted cell proliferation, cell cycle and inhibited cell apoptosis in PCa cells.

<p>(A) The efficiency of siGAS5 was confirmed by qRT-PCR. (B) Knockdown of GAS5 inhibited the proliferation of LNCaP cells. (C) Cell cycle assay was performed in LNCaP cells. Cells were transfected with NC or siGAS5, stained with PI and evaluated with FACScalibur flow cytometer. Knockdown of GAS5 inhibited cell cycle. (D) Cell apoptosis assay was performed in PC-3 cells. Cells were transfected with si-NC or si-GAS5, stained with PI and FITC. GAS5 knockdown increased the percentage of cells in both early apoptosis and late apoptosis. The cell cycle and apoptosis analysis results presented as mean ± SD (n = 3). Significance was defined as p < 0.05 (*p < 0.05; **p < 0.01; ***p < 0.001).</p

The expression of GAS5 in prostate cancer.

<p>(A) The relative expression level of GAS5 in tumor tissue compared with normal tissue in public gene expression data GSE8511, GSE55945 (B) and GSE38241 (C). (D) The relative mRNA level of GAS5 in 52 normal tissue samples compared with 419 tumor tissue samples from TCGA database. (E) Relative expression level of GAS5 was measured in normal prostate epithelial cell line WPMY-1 and four prostate cancer cell lines, LNCaP, 22RV1, DU145 and PC-3 by qRT-PCR. (F) The relative expression of GAS5 in 11 normal prostate tissues and 14 prostate tumor tissues were measured by qRT-PCR. Statistical analyses between groups were performed using an ANOVA analysis. Significance was defined as p < 0.05 (*, p < 0.05; **, p < 0.01; ***, p < 0.001).</p

The regulation of AR on the expression of LncRNA GAS5.

<p>(A) qRT-PCR analysis of GAS5’s expression in LNCaP cells treated with DHT in time series of 0h, 2h, 8h, 24h, 48h. (B) qRT-PCR analysis of GAS5’s expression in LNCaP cells treated with DHT in dose series of 0nM, 0.1nM, 1nM, 10nM, 100nM, 1000nM. (C) The efficiency of siAR on the expression of AR was confirmed by qRT-PCR and the expression of GAS5 was tested after transfection of siAR compared with NC in LNCaP cells. (D) The correlation of mRNA level between GAS5 and AR. (E) The correlation of regulation between GAS5 and AR. Significance was defined as p < 0.05 (*p < 0.05; **p < 0.01; ***p < 0.001).</p