Comprehensive assessment of multiple tryptophan metabolites as potential biomarkers for immune checkpoint inhibitors in patients with non-small cell lung cancer.

PURPOSE: Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity. METHODS: Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). RESULTS: The 19 patients with NSCLC had significantly lower levels of tryptophan (p = 0.002) and xanthurenic acid (p = 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (p = 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (p = 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity: 87.5% and specificity: 83.3%). The patients with 3-HAA < 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months, p = 0.022). CONCLUSIONS: Tryptophan metabolites may have a potential for predicting the efficacy of ICIs. REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trial Registry 000026140.

Full-length sequence of the genome of hepatitis C virus type 3a: comparative study with different genotypes.

Hepatitis C virus (HCV) type K3a (type 3a), which represents a minor genotype in Europe, the U.S.A. and Asia, appears to be significantly distributed throughout Australia and Brazil. We amplified the HCV-K3a/650 genome by reverse transcription polymerase chain reaction in ten overlapping fragments and determined the nucleotide sequences. The total sequence was 9454 bases in length and contained an open reading frame of 3021 amino acids, which is 10 or 11 amino acids longer than in HCV type 1 and 12 amino acids shorter than the sequence of type 2. These differences were due to the different lengths of both the putative envelope protein E2 and the NS5A regions, whose nucleotide lengths differ between types 1 and 2 also. Phylogenetic analysis of the putative core region and a portion of NS5B encoding the Gly-Asp-Asp motif indicated that HCV-K3a closely matched the corresponding type 3a group. The deletion and addition of amino acids in both E2 and NS5A may be associated with their pathobiological features.

Differences in the hepatitis C virus genotypes in different countries.

We recently classified the hepatitis C virus (HCV) into 4 types (HCV-PT, -K1, -K2a and -K2b) according to differences in nucleotide sequences. It was found that HCV-PT, the prototype reported from the U.S.A., was rare in Japan, suggesting that distribution of HCV genotypes may be different in various countries. The prevalence of HCV genotypes was therefore compared in different countries. Genotyping of HCV was performed by slot-blot hybridization analysis using cDNA probes specific to each type of HCV or by restriction fragment length polymorphism analysis. In 121 Japanese non-cancer patients, the prevalence of HCV genotypes was 77.7% for HCV-K1, 16.5% for HCV-K2a and 5.0% for HCV-K2b. HCV-PT was detected in only 1 patient (0.8%). The prevalence in 43 Japanese hepatocellular carcinoma (HCC) patients was 74.4% for HCV-K1, 18.6% for HCV-K2a and 4.7% for HCV-K2b. HCV-PT was found in only 1 sample. In 19 European non-cancer patients, HCV-PT was found in 42.1% and HCV-K1 was found in 52.6%. HCV-K2 was not found. All 7 samples from European HCC patients were HCV-K1, indicating a significantly higher prevalence than in non-cancer patients. In 13 Brazilian non-cancer patients, the distribution pattern was similar to that of the Europeans. In 10 samples from the U.S.A., HCV-PT was found in 70% and HCV-K2 was found in 1 sample. In 18 Chinese non-cancer patients, HCV-K1 was found in 44.4%, HCV-K2a in 50.0% and HCV-K2b in 5.6% HCV-PT was not found. Two samples from Chinese HCC patients were HCV-K1.(ABSTRACT TRUNCATED AT 250 WORDS)