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CD8A encodes the CD8 alpha chain of αβT cells, which has been proposed as a quantifiable indicator for the assessment of CD8+ cytotoxic T lymphocytes (CTLs) recruitment or activity and a robust biomarker for anti-PD-1/PD-L1 therapy responses. Nonetheless, the lack of research into the role of CD8A in tumor microenvironment predisposes to limitations in its clinical utilization. In the presented study, multiple computational tools were used to investigate the roles of CD8A in the pan-cancer study, revealing its essential associations with tumor immune infiltration, immunosuppressive environment formation, cancer progression, and therapy responses. Based on the pan-cancer cohorts of the Cancer Genome Atlas (TCGA) database, our results demonstrated the distinctive CD8A expression patterns in cancer tissues and its close associations with the prognosis and disease stage of cancer. We then found that CD8A was correlated with six major immune cell types, and immunosuppressive cells in multiple cancer types. Besides, epigenetic modifications of CD8A were related to CTL levels and T cell dysfunctional states, thereby affecting survival outcomes of specific cancer types. After that, we explored the co-occurrence patterns of CD8A mutation, thus identifying RMND5A, RNF103-CHMP3, CHMP3, CD8B, MRPL35, MAT2A, RGPD1, RGPD2, REEP1, and ANAPC1P1 genes, which co-occurred mutations with CD8A, and are concomitantly implicated in the regulation of cancer-related pathways. Finally, we tested CD8A as a therapeutic biomarker for multiple antitumor agents’ or compounds’ responsiveness on various cancer cell lines and cancer cohorts. Our findings denoted the underlying mechanics of CD8A in reflecting the T-cell-inflamed profiles, which has potential as a biomarker in cancer diagnosis, prognosis, and therapeutic responses.

Abstract Background The scale degeneration is thought to be related to the adaptation to the extreme environment with cold climate and high-altitude in schizothoracine fishes. Gymnocypris eckloni, a schizothoracine fish living in plateau waters with the elevation above 2500 m, is nearly esquamate and only covered with shoulder scales and anal scales, making it a good model species to study the molecular mechanism of scale degeneration. Results The transcriptomes of shoulder scaled skins (SSS), anal scaled skins (ASS) and scaleless skins (NSS) were sequenced and analyzed in G. eckloni at the age of 1 year. Histological examination showed that shoulder scale had completed its differentiation and anal scale just initiated the differentiation. A total of 578,046 unigenes were obtained from the transcriptomes, with 407,799 unigenes annotated in public databases. A total of 428 and 142 differentially expressed unigenes (DEUs) were identified between SSS and NSS, and between ASS and NSS, respectively, with 45 DEUs that were overlapped. Annotation analysis indicated that these DEUs were mainly enriched in Gene Ontology (GO) terms and KEGG pathways associated with bone and muscle formation, such as myofibril, contractile fiber, cytoskeletal protein binding, muscle structure development, cardiac muscle contraction, hypertrophic cardiomyopathy (HCM) and calcium signaling pathway. Conclusions Our results would provide insights into the molecular mechanisms of scale degeneration in G. eckloni and other congeneric fishes. In addition, the transcriptome data provides candidate genes and markers for future studies.

Cytochrome B (Cyt B) gene and control region of mitochondrial DNA are considered important for evaluating phylogenetic association of a species. In this study, we sequenced Cyt B and control region of Schizothorax plagiostomus and constructed phylogenetic association tree of S. plagiostomus with 23 schizothoracine fishes. We found S. plagiostomus to be closely associated with S. labiatus, S. richardsonii, S. progastus, and S. esocinus, with high-bootstraps values. Several conserved sequence blocks were identified within D-loop sequences. These are highly conserved within genus Schizothorax compared to other. This study reports the phylogenetic position of the S. plagiostomus among schizothoracines fishes and organization of D-loop region in S. plagiostomus from Pakistan.

The complete mitogenome of Triplophysa cuneicephala is 16,571 bp in length with the A + T contents of 56.12%, containing 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and a putative control region. All PCGs employed ATG as the start codon, except for COI which utilized GTG as start codon. Four stop codons were observed in the PCGs, including TAA, TAG, TA and T. Phylogenetic analysis based on concatenated PCG sequences revealed that T. cuneicephala is closely related to T. robusta and T. minxianensis. This study would provide useful genetic information for future studies on phylogeny, evolutionary, and taxonomic classification in Triplophysa species.

The complete mitochondrial genome of Triplophysa sellaefer is a circular molecule of 16,571 bp in length with the A + T contents of 56.84%, containing 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes, and a putative control region. Six gene overlaps and 10 intergenic spacers were observed, with the total length of 26 bp and 34 bp, respectively. The phylogenetic analysis based on the concatenated PCG sequences revealed that T. sellaefer is closely related to T. alticeps. This study would provide useful information on phylogenetic and evolutionary studies in Triplophysa.