Modern accumulations of genetic data offer unprecedented opportunities for understanding the systematic classification and origins of specific groups of organisms. The genus Sinocyclocheilus is among the most cave abundant genera in Cyprinidae, with 76 recognized species, belonging to 4 species groups. Recent phylogenetic studies have shown that the classification of species groups within the genus Sinocyclocheilus remains controversial. In this study, we constructed a sequence supermatrix of 26 species from 4 species groups of the genus Sinocyclocheilus using the mitochondrial genome to reveal phylogenetic relationships, historical biogeography and patterns of species diversification in the genus Sinocyclocheilus. Phylogenetic analysis strongly supports the monophyletic groups of the 3 species groups (S. jii, S. cyphotergous, and S. tingi groups) except the S. angularis group. Phylogenetic analysis showed that S. anshuiensis and S. microphthalmus, which were recognized as numbers of S. angularis group, formed a strongly supported independent clade. Therefore, we propose a new species group, the S. microphthalmus group, which contains S. anshuiensis and S. microphthalmus. Biogeographic reconstruction suggests that the living Sinocyclocheilus may have originated in north‐central Guangxi at the late Eocene and dispersed outward after a vicariance at 32.31 Million years ago (Ma). Early diversification is focused on the late Oligocene (ca. 25 Ma), which is related to the second uplift of the Qinghai−Tibetan Plateau and the lateral extrusion of the Indochina at the Oligocene/Miocene boundary. Our results suggest that 2 uplifts of the Qinghai−Tibetan Plateau and climate change in the Miocene may have influenced the diversification of the Sinocyclocheilus lineage.
Background
Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer.
Methods
The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored.
Results
Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%; P = 0.00057), and remained significant after a multiple comparison adjustment (Padjusted = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827−0.997) was achieved in the integrated model.
Conclusions
Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy.
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