Alterations of mitochondrial DNA (mtDNA) have been identified in several types of solid tumor. However, to the best of our knowledge, the clinical significance of plasma mtDNA content in lung cancer remains unknown. Thus, the current study explored the diagnostic and prognostic value of plasma mtDNA quantification in patients with lung cancer. Plasma mtDNA copy numbers of patients with lung cancer (n=128) and healthy individuals (n=107) were quantified by quantitative polymerase chain reaction. Plasma mtDNA copy numbers in patients and healthy controls were 0.89×104 and 1.37×104 copies/µl, respectively (P<0.0001). Furthermore, lower plasma mtDNA content was associated with tumor size, lymph node metastases, distant metastases and serum carcinoembryonic antigen levels (P<0.05), but was not associated with pathological type, age, sex or main driver gene mutation status (P>0.05). Plasma mtDNA facilitated the detection of lung cancer at a threshold of 1.19×104 copies/µl with a sensitivity of 71.1% and specificity of 70.1%, as determined by receiver operating characteristic curve analysis. Advanced stage (III and IV) patients with a lower mtDNA copy number (cutoff: 1.02×104 copies/µl) tended to exhibit poorer prognosis (P<0.05). These results indicated that plasma mtDNA content is a promising and complementary candidate with tissue mtDNA for diagnosis and prognostic prediction for lung cancer.

The pathogenicity of the common phytopathogenic bacterium Pseudomonas syringae toward Caenorhabditis elegans has been recently demonstrated. However, the major virulence factors involved in this interaction remain unknown. In this study, we investigated the nematocidal activity of P. syringae against C. elegans under iron-sufficient/limited conditions, primarily focusing on the role of the ferric chelator pyoverdine in a P. syringae–C. elegans liquid-based pathogenicity model. Prediction-based analysis of pyoverdine-encoding genes in the genome of the wild-type P. syringae strain MB03 revealed that the genes are located in one large cluster. Two non-ribosomal peptide synthetase genes (pvdD and pvdJ) were disrupted via a Rec/TE recombination system, resulting in mutant strains with abrogated pyoverdine production and attenuated virulence against C. elegans. When used alone, pure pyoverdine also showed nematocidal activity. The role of iron used alone or with pyoverdine was further investigated in mutant and MB03-based bioassays. The results indicated that pyoverdine in P. syringae MB03 is a robust virulence factor that promotes the killing of C. elegans. We speculate that pyoverdine functions as a virulence determinant by capturing environmentally available iron for host bacterial cells, by limiting its availability for C. elegans worms, and by regulating and/or activating other intracellular virulence factors that ultimately kills C. elegans worms.

Stomatin-like protein 2 (SLP-2) is associated with poor prognosis in several types of cancer, including pancreatic cancer (PC); however, the molecular mechanism of its involvement remains elusive. The present study aimed to elucidate the role of this protein in the development of PC. Human PC cell lines AsPC-1 and PANC-1 were transfected by a vector expressing SLP-2 shRNA. Analyses of cell proliferation, migration, invasion, chemosensitivity, and glucose uptake were conducted, while a mouse xenograft model was used to evaluate the functional role of SLP-2 in PC. Immunohistochemical analysis was retrospectively performed on human tissue samples to compare expression between the primary site (n=279) and the liver metastatic site (n=22). Furthermore, microarray analysis was conducted to identify the genes correlated with SLP-2. In vitro analysis demonstrated that cells in which SLP-2 was suppressed exhibited reduced cell motility and glucose uptake, while in vivo analysis revealed a marked decrease in the number of liver metastases. Immunohistochemistry revealed that SLP-2 was increased in liver metastatic sites. Microarray analysis indicated that this protein regulated the expression of glutamine-fructose-6-phosphate transaminase 2 (GFPT2), a rate-limiting enzyme of the hexosamine biosynthesis pathway. SLP-2 contributed to the malignant character of PC by inducing liver metastasis. Cell motility and glucose uptake may be induced via the hexosamine biosynthesis pathway through the expression of GFPT2. The present study revealed a new mechanism of liver metastasis and indicated that SLP-2 and its downstream pathway could provide novel therapeutic targets for PC.

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