Table_1_Case report: Target and immunotherapy of a lung adenocarcinoma with enteric differentiation, EGFR mutation, and high microsatellite instability.xlsx

BackgroundPulmonary enteric adenocarcinoma (PEAC) is a rare histological subtype of non-small-cell lung cancer (NSCLC) with a predominant (>50%) enteric differentiation component. The frequency of high microsatellite instability (MSI-H) is very low in lung cancer. EGFR tyrosine kinase inhibitors and immunotherapy are standard treatment for NSCLC patients, but their effectiveness in lung adenocarcinoma with pulmonary enteric differentiation is unknown.Case presentationThis report describes a 66-year-old man who was initially diagnosed with metastatic lung adenocarcinoma with EGFR mutation based on pleural fluid. A lung biopsy was obtained after 17 months of first-line icotinib treatment. Histological analysis of biopsy samples and endoscopic examination resulted in a diagnosis of adenocarcinoma with enteric differentiation. Next-generation sequencing of 1,021 genes showed EGFR E19del, T790M, and MSI-H, while immunohistochemical assay showed proficient expression of mismatch repair (MMR) proteins. Consequently, the patient was treated with osimertinib and had a progression-free survival (PFS) of 3 months. His treatment was changed to chemotherapy with/without bevacizumab for 6.5 months. Then, the patient was treated with one cycle of camrelizumab monotherapy and camrelizumab plus chemotherapy, respectively. The tumor continued to grow, and the patient suffered pneumonia, pulmonary fungal infections, and increased hemoptysis. He received gefitinib and everolimus and died 2 months later and had an overall survival of 30 months.ConclusionIn summary, our case describes a rare pulmonary enteric adenocarcinoma with an EGFR-activating mutation and MSI-H, responding to an EGFR tyrosine kinase inhibitor and poorly benefiting from an immune checkpoint inhibitor.</p

Table_2_Case report: Target and immunotherapy of a lung adenocarcinoma with enteric differentiation, EGFR mutation, and high microsatellite instability.docx

BackgroundPulmonary enteric adenocarcinoma (PEAC) is a rare histological subtype of non-small-cell lung cancer (NSCLC) with a predominant (>50%) enteric differentiation component. The frequency of high microsatellite instability (MSI-H) is very low in lung cancer. EGFR tyrosine kinase inhibitors and immunotherapy are standard treatment for NSCLC patients, but their effectiveness in lung adenocarcinoma with pulmonary enteric differentiation is unknown.Case presentationThis report describes a 66-year-old man who was initially diagnosed with metastatic lung adenocarcinoma with EGFR mutation based on pleural fluid. A lung biopsy was obtained after 17 months of first-line icotinib treatment. Histological analysis of biopsy samples and endoscopic examination resulted in a diagnosis of adenocarcinoma with enteric differentiation. Next-generation sequencing of 1,021 genes showed EGFR E19del, T790M, and MSI-H, while immunohistochemical assay showed proficient expression of mismatch repair (MMR) proteins. Consequently, the patient was treated with osimertinib and had a progression-free survival (PFS) of 3 months. His treatment was changed to chemotherapy with/without bevacizumab for 6.5 months. Then, the patient was treated with one cycle of camrelizumab monotherapy and camrelizumab plus chemotherapy, respectively. The tumor continued to grow, and the patient suffered pneumonia, pulmonary fungal infections, and increased hemoptysis. He received gefitinib and everolimus and died 2 months later and had an overall survival of 30 months.ConclusionIn summary, our case describes a rare pulmonary enteric adenocarcinoma with an EGFR-activating mutation and MSI-H, responding to an EGFR tyrosine kinase inhibitor and poorly benefiting from an immune checkpoint inhibitor.</p

Principal component analysis of retroelements in the <i>L. migratoria</i> transcriptome.

<p>Two phases in the same developmental stage are plotted with the same colours.</p

Phylogenetic relationships of the <i>gypsy</i> retrotransposons.

<p>Phylogenetic relationships were inferred by the neighbour-joining method. This tree was constructed from the reverse transcriptase sequences using the neighbour-joining method. Bootstrap values of more than 50 are shown in the branches. The known retrotransposons from other species were retrieved from the GenBank and Repbase databases. The sequences in red indicate the <i>gypsy</i> retroelements identified in this study.</p

Global phylogenetic trees using all identified retroelements of reverse transcriptase sequences in the <i>L. migratoria</i> transcriptome.

<p>The red circles indicate the retroelement identified in this study. The names of elements from previously described retrotransposons are given.</p

Large-Scale Transcriptome Analysis of Retroelements in the Migratory Locust, <em>Locusta migratoria</em>

<div><h3>Background</h3><p>Retroelements can successfully colonize eukaryotic genome through RNA-mediated transposition, and are considered to be some of the major mediators of genome size. The migratory locust <em>Locusta migratoria</em> is an insect with a large genome size, and its genome is probably subject to the proliferation of retroelements. An analysis of deep-sequencing transcriptome data will elucidate the structure, diversity and expression characteristics of retroelements.</p> <h3>Results</h3><p>We performed a <em>de novo</em> assembly from deep sequencing RNA-seq data and identified 105 retroelements in the locust transcriptome. Phylogenetic analysis of reverse transcriptase sequences revealed 1 <em>copia</em>, 1 BEL, 8 <em>gypsy</em> and 23 non-long terminal repeat (LTR) retroelements in the locust transcriptome. A novel approach was developed to identify full-length LTR retroelements. A total of 5 full-length LTR retroelements and 2 full-length non-LTR retroelements that contained complete structures for retrotransposition were identified. Structural analysis indicated that all these retroelements may have been activated or deprived of retrotransposition activities very recently. Expression profiling analysis revealed that the retroelements exhibited a unique expression pattern at the egg stage and showed differential expression profiles between the solitarious and gregarious phases at the fifth instar and adult stage.</p> <h3>Conclusion</h3><p>We hereby present the first <em>de novo</em> transcriptome analysis of retroelements in a species whose genome is not available. This work contributes to a comprehensive understanding of the landscape of retroelements in the locust transcriptome. More importantly, the results reveal that non-LTR retroelements are abundant and diverse in the locust transcriptome.</p> </div

Transcriptional composition of the <i>L. migratoria</i> transcriptome.

<p>The values on the x-axis correspond to the divergence rates, and the values on the y-axis are the total transcriptional abundance.</p

Strategy for the identification and characterization of full-length LTR retroelements in the <i>L. migratoria</i> transcriptome.

<p>Rectangles indicate protein domains. The polylines in step 4 and 6 indicate the paired-end reads. The misassembled LTR retroelement is presented at the top of the figure.</p

Phylogenetic relationships among the 12 well-established clades of non-LTR retrotransposons.

<p>Three newly identified clades, Vingi, Nimb and Daphne, were also included. This tree was constructed from the reverse transcriptase sequences using the neighbour-joining method. Bootstrap values less than 50 are not shown. The known retrotransposons from other species were retrieved from the GenBank and Repbase databases. The sequences in red indicate the non-LTR retroelements identified in this study.</p

Highly expressed retroelements in fourth instar nymphs of solitarious locusts.

<p>Highly expressed retroelements in fourth instar nymphs of solitarious locusts.</p