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Most cancers are caused by somatic mutations. Some common mutations in the same cancer type can form a "signature" to specifically predict the prognosis or to distinguish it from other cancers. In this study, 710 somatic cell mutations were identified in 142 cases, including digestive, lung and urogenital cancers, and the digestive cancers were further divided into liver, stomach, intestinal, esophageal and cardia cancer. The above mutations were located in 166 genes. In addition, a group of high-frequency mutation genes with specific characteristics were screened to form predictive signatures for each cancer. Verification using TCGA suggested that the signatures could predict the stages, progression-free survival, and overall survival of digestive, intestinal, and liver cancers (P 0.05). The validation cases further confirmed the predictive role of digestive and liver cancers signatures in diagnosis and prognosis. Overall, this study established predictive signatures for different cancer systems and their subtypes. These findings enable a better understanding in cancer genome, and contribute to the personalized diagnosis and treatment.

Stomata are leaf pores that regulate gas exchange and water transpiration in response to environmental cues. They also function in innate immunity by limiting pathogen entry through actively closing in so-called stomatal defense. However, roles of stomata in plant disease resistance are not fully elucidated, especially in monocots. Here, we report that non–race specific resistance of the rice abscisic acid-deficient mutant Osaba1 to Xanthomonas oryzae pv. oryzae is due to increased stomatal conductance. Reducing stomatal conductance in the Osaba1 mutant increases its susceptibility to X. oryzae pv. oryzae. Artificial opening of stomata in wild-type plants leads to enhanced resistance to X. oryzae pv. oryzae. The rice mutant es1-1 with constitutively higher stomatal conductance exhibits strong resistance to X. oryzae pv. oryzae. Additionally, Osaba1 and es1-1 are resistant to X. oryzae pv. oryzicola. The data support that open stomata confer postinvasive resistance against bacterial pathogens in rice, and such resistance probably results from decreased leaf water potential. Our findings reveal a novel role of stomata in plant immunity through modulation of leaf water status, which provides physiological insight into the interactions between plant, pathogen, and environment.

Background The purpose of this study was to construct a new typing model for diffuse large B-cell lymphoma (DLBCL) patients based on the B-cell receptor (BCR) and explore its potential molecular mechanism. Methods BCR repertoire sequencing and whole-exome sequencing were performed on formalin-fixed paraffin-embedded samples from 12 DLBCL patients. Subsequently, a typing model was built with cluster analysis, and prognostic indicators between the two groups were compared to verify the typing model. Then, mutation and bioinformatics analyses were conducted to investigate the potential biomarkers of prognostic differences between the two groups. Results Based on BCR sequencing data, we divided patients into two clusters (cluster 1 and cluster 2); this classification differed from the traditional typing method (GCB and non-GCB), in which cluster 1 included some non-GCB patients. The progression-free survival (PFS), overall survival (OS), metastasis and Shannon diversity index of IGH V-J and survival after chemotherapy were significantly different (P FTSJ3, MAGED2, and ODF3L2 were the specific mutated genes in all patients in cluster 2, and these genes could be considered critical to the different prognoses of the two clusters of DLBCL patients. Conclusion We constructed a new typing model of DLBCL based on BCR repertoire sequencing that can better predict the survival time after chemotherapy. FTSJ3, MAGED2, and ODF3L2 may represent key genes for the difference in prognosis between the two clusters.

High expression of PD-L1 marks the poor prognosis of pancreatic ductal adenocarcinomas (PDAC). However, the regulatory mechanism of PD-L1 remains elusive. We recently reported that cancer Forkhead box protein 3 (Cancer-FOXP3 or C-FOXP3) promoted immune evasion of PDAC by recruiting Treg cells into PDAC via upregulation of CCL5. In this study, we confirmed that PD-L1 was overexpressed in PDAC samples from two independent cohorts of patients with radical resection. Moreover, C-FOXP3 was colocalized and correlated with the expression of PD-L1 in tumor cells at the mRNA and protein levels, and this finding was confirmed by the The Cancer Genome Atlas (TCGA) database. Chromatin immunoprecipitation (ChIP) revealed that C-FOXP3 directly bound to the promoter region of PD-L1 in pancreatic cancer cells. Furthermore, overexpression of C-FOXP3 activated the luciferase reporter gene under the control of the PD-L1 promoter. However, mutation of the binding motif-a completely reversed the luciferase activity. In addition, C-FOXP3-induced upregulation of PD-L1 effectively inhibited the activity of CD8+ T cells. Based on our recent finding that the CCL-5 antibody achieved a better response to PDAC models with high C-FOXP3 levels, we further demonstrated that the PD-L1 antibody strengthened the antitumor effect of CCL-5 blockade in xenograft and orthotopic mouse models with high C-FOXP3 levels. In conclusion, C-FOXP3 directly activates PD-L1 and represents a core transcription factor that mediates the immune escape of PDAC. Combined blockade of PD-L1 and CCL-5 may provide an effective therapy for patients with PDAC that have high C-FOXP3 levels.

e21652 Background: EGFR-TKI application is directed by the situation of mutations of epidermal growth factor receptor, in addition, the mutations of ALK, ROS-1,C-met, BRAF, Her-2, RET,NTRK1, PI3K, MEKI have potential effects on guiding treatment. This study aimed to investigate the uncommon and insensitive mutations and their effect on prognosis in non-small cell lung cancer (NSCLC) patients treated with EGFR-TKI. Methods: 21 NSCLC patients treated with EGFR-TKIs were enrolled, 9 with Gefitinib, 5 with Osimertinib and 7 with Icotinib. All patients were detected with targeted NGS 1000 gene panel. Afterwards, the EGFR sensitive mutation, uncommon mutation and mutations accompanied EGFR T790M were analyzed. Furthermore, the correlations of gene mutation with metastasis, OS and PFS were analyzed. SPSS 21.0 was used for statistical analysis, t test for continuous variables and χ2 test for classified variables. Results: In all the patients, EGFR p.[T790M] and p.[L858R] mutations were detected in 4.76% and 23.81% of the patients, respectively. In the 5 patients treated with Osimertinib, one had EGFR p.[T790M] mutation and curative effects was stable disease (SD). The mutations accompanied EGFR T790M included SMARCA4 p.[K1390Q] (2.23%), DNMT3A p.[F755S] (2.17%), MTOR p.[Y1450*] (2.15%), TPMT p.[L182R] (1.84%), etc. For the other four patients treated with Osimertinib, two of them were partial response (PR) and two were SD, accompanied with mutations such as EGFR p.[L858R] (55.00%), ARID1A p.[P16del] (2.83%), TP53 p.[R248W] (21.73%) and AR p.[Q60L] (4.24%). In addition, among all the mutations, 18 uncommon mutations were detected, in which ATM (23.26%), AR (23.26%) and MTOR (37.21%) were markedly associated with OS. Besides, the mutation frequency of 67 genes, such as ABCG2, AURKA, EPHA3 and ATR were correlated with OS. The mutation frequency of FGFR1 was significantly different between the patients with and without metastasis. The mutations of 22 genes, for instance ABCG2 p.[P21L], FAT1 p.[L398F], GNAS p.[F226V] and KMT2C p.[N2842Ilefs], were correlated with PFS during the treatment. Conclusions: EGFR-TKI has similar curative effects in EGFR p.[T790M] negative patients. Gene mutations, including uncommon mutations and EGFR insensitive mutations, can significantly affect the prognosis in NSCLC patients treated with EGFR-TKIs.

MicroRNAs (miRNAs) are endogenous non-coding small RNAs that silence genes through mRNA degradation or translational inhibition. The phytohormone abscisic acid (ABA) is essential for plant development and adaptation to abiotic and biotic stresses. In Arabidopsis, miRNAs are implicated in ABA functions. However, ABA-responsive miRNAs have not been systematically studied in rice. Here high throughput sequencing of small RNAs revealed that 107 miRNAs were differentially expressed in the rice ABA deficient mutant, Osaba1. Of these, 13 were confirmed by stem-loop RT-PCR. Among them, miR1425-5P, miR169a, miR169n, miR390-5P, miR397a and miR397b were up-regulated, but miR162b reduced in expression in Osaba1. The targets of these 13 miRNAs were predicted and validated by gene expression profiling. Interestingly, the expression levels of these miRNAs and their targets were regulated by ABA. Cleavage sites were detected on 7 of the miRNA targets by 5'-Rapid Amplification of cDNA Ends (5'-RACE). Finally, miR162b and its target OsTRE1 were shown to affect rice resistance to drought stress, suggesting that miR162b increases resistance to drought by targeting OsTRE1. Our work provides important information for further characterization and functional analysis of ABA-responsive miRNAs in rice.

Plants have established a complicated immune defense system during co-evolution with pathogens. The innate immune system of plants can be generally divided into two levels. One, named PAMP-triggered immunity (PTI), is based on the recognition of pathogen-associated molecular patterns by pattern-recognition receptors, which confers resistance to most pathogenic microbes. The other begins in cytoplasm and mainly relies on recognition of microbial effectors by plant resistance proteins in direct or indirect ways, which then initiates potent defense responses. This process, termed effector-triggered immunity (ETI), is necessary for defense against pathogens that can secret effectors to suppress the first level of immunity. Activation of these two layers of immunity in plant is based on distinguishing and recognition of "self" and "non-self" signals. Recognition of "non-self" signals can activate signal cascades, such as MAPK cascades, which will then induce defense gene expression and corresponding defense responses. In this review, we focused on underlying molecular mechanisms of plant-pathogen interactions and the latest advances of the PTI and ETI signaling network.

Leaf rolling is considered an important agronomic trait in rice (Oryza sativa) breeding. To understand the molecular mechanism controlling leaf rolling, we screened a rice T-DNA insertion population and isolated the outcurved leaf1 (oul1) mutant showing abaxial leaf rolling. The phenotypes were caused by knockout of Rice outermost cell-specific gene5 (Roc5), an ortholog of the Arabidopsis (Arabidopsis thaliana) homeodomain leucine zipper class IV gene GLABRA2. Interestingly, overexpression of Roc5 led to adaxially rolled leaves, whereas cosuppression of Roc5 resulted in abaxial leaf rolling. Bulliform cell number and size increased in oul1 and Roc5 cosuppression plants but were reduced in Roc5-overexpressing lines. The data indicate that Roc5 negatively regulates bulliform cell fate and development. Gene expression profiling, quantitative polymerase chain reaction, and RNA interference (RNAi) analyses revealed that Protodermal Factor Like (PFL) was probably down-regulated in oul1. The mRNA level of PFL was increased in Roc5-overexpressing lines, and PFL-RNAi transgenic plants exhibit reversely rolling leaves by reason of increases of bulliform cell number and size, indicating that Roc5 may have a conserved function. These are, to our knowledge, the first functional data for a gene encoding a homeodomain leucine zipper class IV transcriptional factor in rice that modulates leaf rolling.