Concordant point mutation of ETS-related gene (ERG) in tumor tissues from a synchronous multiple primary lung cancer: A case report / 北京大学学报(医学版)

The rearrangement of the gene encoding the transcription factor ETS-related gene (ERG) is thought to play a key role in the development of prostate cancer. However, the studies on the ERG mutations have been rarely reported in non-small cell lung carcinoma (NSCLC). Here, we reported genetic features regarding a case of a 68-year-old male patient who presented the primary synchronous multiple tumor lesions in the separated lungs. The patient was hospitalized due to the presence of tumor lesions at the right and left lungs revealed by a chest computerized tomography (CT) scan. After conducting lobectomies at the both lungs, the tumor nodules were all removed, and the histological analysis suggested adenocarcinoma at the both tumor lesions. The patient was diagnosed with synchronous multiple primary lung cancer (SMPLC) based on Martini-Melamed criteria and American College of Chest Physicians practice guidelines. An exome analysis of 315 genes in the two tumor lesions and a non-tumor lesion was conducted by using Illumina Nextseq500 platform from each tumor region to decipher a potential evolutional progress of SMPLC. Single or pair-end reads were first mapped to a human genome reference and filtered based on the mapping quality score. The read depth was ≥ 1 000× and the depth of coverage was 95%. The data revealed a discordant epidermal growth factor receptor (EGFR) from the separate lungs; additionally, a high frequency of point mutation on exon 9 H310P of the ERG gene was detected at the both sites of the tumor lesions. This case showed that a potential role of the molecular features analysis from each tumor lesion might contribute to the understanding of the evolutional development of SMPLC. This study suggests that the same environment may contribute certain gene(s) mutations in the same sites in the early stages of polyclonal tumor origins; meanwhile the extensive studies on these genes may help us understand the evolution and progress of tumor clones.

Expression of PD1 and BTLA on the CD8+ T Cell and γδT Cell Subsets in Peripheral Blood of Non-Small Cell Lung Cancer Patients / 中国医学科学杂志(英文版)

Objective To investigate the expression and regulation of programmed cell death protein 1 (PD1), B lymphocyte and T lymphocyte attenuator (BTLA) in peripheral blood of patients with non-small cell lung cancer (NSCLC); to examine the correlation of the mRNA levels between PD and BTLA in NSCLC. Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8+ T cells and γδ+ T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals. We compared the expression of PD1 and BTLA on the surfaces of γδ+ T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid. The correlations of PD1 and BTLA, as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform. Results The frequency of PD1 on the surfaces of CD8+ T cells was significantly higher than that of the γδT cells in both healthy controls (t=2.324, P=0.024) and NSCLC patients（t=2.498, P=0.015). The frequency of PD1 on CD8+ T cells, rather than on γδ+ T cells, was significantly upregulated in advanced NSCLC patients compared with that in healthy controls (t=4.829, P<0.001). The PD1+ BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients (t=2.422, P=0.0185). No differences in percentage of PD1+γδ+ and BTLA+γδ+ T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment. PD1 was positively correlated with BTLA in both lung adenocarcinoma (r=0.54; P<0.05) and lung squamous cell carcinoma (r=0.78; P<0.05). Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8+ T cells and γδT cells in advanced NSCLC, suggesting that these molecules were involved in regulating the inactivation of CD8+ T cells and γδ+ T cells, immune escape and tumor invasion.

Low trichorhinophalangeal syndrome 1 gene transcript levels in basal-like breast cancer associate with mesenchymal-to-epithelial transition / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate trichorhinophalangeal syndrome 1 gene (TRPS-1) expression patterns in different subtypes of breast cancer and its correlations with other genes and survival using microarray data sets.</p><p><b>METHODS</b>The transcripts of TRPS-1 and its role in survival in breast cancer were analyzed using published microarray data sets#x02014;Netherlands Cancer Institute (NKI) cohort and Wang cohort.</p><p><b>RESULTS</b>TRPS-1 expression was lower in basal-like breast cancer. The mRNA levels of TRPS-1 negatively correlated with Slug (Pearson correlation coefficient=-0.1366, P=0.0189 in NKI data set and Pearson correlation coefficient=-0.1571, P=0.0078 in Wang data set), FOXC1 (Pearson correlation coefficient=-0.1211, P=0.0376 in NKI data set and Pearson correlation coefficient=-0.1709, P=0.0037 in Wang data set), and CXCL1 (Pearson correlation coefficient=-0.1197, P=0.0399 in NKI data set and Pearson correlation coefficient=-0.3436, P<0.0001 in Wang data set), but positively correlated with BRCA1 (Pearson correlation coefficient=0.1728, P=0.0029 in NKI data set and Pearson correlation coefficient=0.1805, P=0.0022 in Wang data set). Low TRPS-1 expression associated with poor overall survival (hazard ratio 1.79, 95% CI of ratio 0.9894 to 3.238, P=0.054) and relapse-free survival (hazard ratio 1.913, 95% CI of ratio 1.159 to 3.156, P<0.05). The low TRPS-1 mRNA levels predicted poor outcome in breast cancer patients by the 70-gene signature.</p><p><b>CONCLUSION</b>The strong expression of TRPS-1 may serve as a good prognostic marker in breast cancer.</p>