Miaomiao Li

Recent studies suggest that the human microbiome influence tumor development. Endometrial carcinoma (EC) is the sixth most common malignancy in women. Recent research has demonstrated the microbes play a critical role in the development and metastasis of EC. However, it remains unclear whether intratumoral microbes are associated with tumor microenvironment (TME) and prognosis of EC. In this study, we collected the EC microbiome data from cBioPortal and constructed a prognostic model based on Resident Microbiome of Endometrium (RME). We then examined the relationship between the RME score, immune cell infiltration, immunotherapy-related signature, and prognosis. The findings demonstrated the independent prognostic value of the RME score for EC. The group with low RME scores had higher enrichment of immune cells. Drug sensitivity analysis revealed that the RME score may serve as a potential predictor of chemotherapy efficacy. In conclusion, our research offers new perspectives on the relationships between tumor immunity and microbes.

Patients with antiretroviral therapy interruption have a high risk of virological failure when re-initiating antiretroviral therapy (ART), especially those with HIV drug resistance. Next-generation sequencing may provide close scrutiny on their minority drug resistance variant. A cross-sectional study was conducted in patients with ART interruption in five regions in China in 2016. Through Sanger and next-generation sequencing in parallel, HIV drug resistance was genotyped on their plasma samples. Rates of HIV drug resistance were compared by the McNemar tests. In total, 174 patients were included in this study, with a median 12 (interquartile range (IQR), 6–24) months of ART interruption. Most (86.2%) of them had received efavirenz (EFV)/nevirapine (NVP)-based first-line therapy for a median 16 (IQR, 7–26) months before ART interruption. Sixty-one (35.1%) patients had CRF07_BC HIV-1 strains, 58 (33.3%) CRF08_BC and 35 (20.1%) CRF01_AE. Thirty-four (19.5%) of the 174 patients were detected to harbor HIV drug-resistant variants on Sanger sequencing. Thirty-six (20.7%), 37 (21.3%), 42 (24.1%), 79 (45.4%) and 139 (79.9) patients were identified to have HIV drug resistance by next-generation sequencing at 20% (v.s. Sanger, p = 0.317), 10% (v.s. Sanger, p = 0.180), 5% (v.s. Sanger, p = 0.011), 2% (v.s. Sanger, p < 0.001) and 1% (v.s. Sanger, p < 0.001) of detection thresholds, respectively. K65R was the most common minority mutation, of 95.1% (58/61) and 93.1% (54/58) in CRF07_BC and CRF08_BC, respectively, when compared with 5.7% (2/35) in CRF01_AE (p < 0.001). In 49 patients that followed-up a median 10 months later, HIV drug resistance mutations at >20% frequency such as K103N, M184VI and P225H still existed, but with decreased frequencies. The prevalence of HIV drug resistance in ART interruption was higher than 15% in the survey. Next-generation sequencing was able to detect more minority drug resistance variants than Sanger. There was a sharp increase in minority drug resistance variants when the detection threshold was below 5%.

In our study, we reported a novel CRF01_AE/B/C human immunodeficiency virus type 1 (HIV-1) recombinant form among six epidemiologically unlinked heterosexual patients in Yunnan, China. It was named CRF106_cpx (this is temporary as we have not received the circulating recombinant form [CRF] number from HIV databases). After sequencing and analyzing of the near full-length genome, we found that CRF106_cpx was generated by three B segments and two CRF01_AE segments inserted into the C backbone. There was quite a bit of diversity between sequences of CRF106_cpx, so this seems to be a CRF that has been spreading for many years.