title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=315 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Retrospective analysis of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), Ki67 changes and their clinical significance between primary breast cancer and metastatic tumors link: https://peerj.com/articles/17377 last-modified: 2024-05-15 description: ObjectiveTo explore the relationship between receptor heterogeneity and clinicopathological characteristics in 166 patients with invasive breast cancer during metastasis.MethodsWe conducted a retrospective analysis of 166 patients diagnosed with metastatic breast cancer through biopsy, who were admitted to our hospital from January 2018 to December 2022. Statistical analysis was employed to assess the heterogeneity of receptors in both primary and metastatic lesions, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), Ki67, as well as their association with clinicopathological features such as tumor size, lymph node metastasis, treatment regimen, and disease-free survival.ResultsThe discordant expression rates of ER, PR, HER2, Ki-67 and Luminal classification between primary and metastatic lesions were 21.7%, 41.6%, 8.9%, 34.4% and 36.8%, respectively. There is a significant difference in disease-free survival between patients with consistent and inconsistent receptor status of primary and metastatic lesions, which is statistically significant. The median DFS for primary HER2(-) to metastatic HER2(+) was 84 months, which was relatively high. The Cox multivariate regression analysis revealed that the expression differences of ER, PR, HER2, and Ki67 were not influenced by endocrine therapy and chemotherapy. However, a statistically significant difference in HER2 expression was observed with targeted therapy. Tumor size was correlated with ER and Ki67 receptor status (P = 0.019, 0.016). Tumor size was not correlated with PR, and HER2 (P = 0.679, 0.440). Lymph node metastasis was not associated with changes in ER, PR, HER2, and Ki67. The discordant rates of ER, PR, HER2, and Ki-67 in patients with local recurrence were 22%, 23.7%, 5.1%, and 28.8% respectively, whereas those in patients with distant metastasis were 21.5%, 36.4%, 10.3%, and 31.8% respectively.ConclusionsThe expression levels of ER, PR, HER2, and Ki-67 in primary and metastatic breast cancer exhibit heterogeneity, which is closely associated with the prognosis and treatment outcomes of patients. creator: Gaoxiu Qi creator: Xin Zhang creator: Xiaoying Gai creator: Xiong Yan uri: https://doi.org/10.7717/peerj.17377 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2024 Qi et al. title: The prognostic value of preoperative neoindices consisting of lymphocytes, neutrophils and albumin (LANR) in operable breast cancer: a retrospective study link: https://peerj.com/articles/17382 last-modified: 2024-05-15 description: BackgroundPreoperative inflammatory factors and nutritional status are strongly associated with the prognosis of a variety of cancers. We explored the relationship between preoperative lymphocytes, neutrophils and albumin (LANR) and progression-free survival in breast cancer patients.MethodsThe clinical and follow-up data of 200 breast cancer patients were retrospectively analyzed in this study, and the value of LANR was determined as follows: LANR, lymphocytes × albumin/neutrophils. ROC curves, COX proportional risk regression analysis and subgroup analysis were used to assess the prognostic value of LANR in progression-free survival of breast cancer patients.ResultsThe median age of the patients was 55.5 years (range 50–62 years). The median follow-up time was 46 months (range 33–55 months). In progression-free survival, the area under the LANR curve was 0.748 and the HR (95% CI) was 0.035 (0.679–0.817). LANR was associated with age (p = 0.02), positive axillary lymph nodes (p < 0.001), TNM stage (p < 0.001) and human epidermal growth factor receptor 2(p = 0.004). The results indicated that preoperative LANR may be a reliable predictor of progression-free survival in patients with operable breast cancer.ConclusionLANR may be an essential predictor for breast cancer patients and provides a therapeutic basis for clinicians and patients. creator: Yuan Wang creator: Jiaru Zhuang creator: Shan Wang creator: Yibo Wu creator: Ling Chen uri: https://doi.org/10.7717/peerj.17382 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2024 Wang et al. title: Var3PPred: variant prediction based on 3-D structure and sequence analyses of protein-protein interactions on autoinflammatory diseases link: https://peerj.com/articles/17297 last-modified: 2024-05-14 description: We developed a pathogenicity classifier, named Var3PPred, for identifying pathogenic variants in genes associated with autoinflammatory disorders. Our comprehensive approach integrates protein-protein interaction analysis and 3D structural information. Initially, we collected a dataset of 702 missense disease-associated variants from 35 genes linked to systemic autoinflammatory diseases (SAIDs). This dataset, sourced from the Infevers database, served as the training and test sets. We used the SMOTE algorithm to balance the dataset comprising 130 benign and 572 pathogenic variations. Our approach included 3D docking analysis of protein-protein interactions, utilizing data from the STRING and Intact databases. We weighted ZDOCK and SPRINT values in accordance with HGPEC gene rank scores for robustness. Additionally, we integrated sequential and structural features, such as changes in folding free energies (ΔΔ G), accessible surface area, volume, per residue local distance difference test (pLDDT) scores, and position specific independent count (PSIC) scores. These features, calculated using PyRosetta and AF2 computed structures, provided insights into amino acid conservation at variant positions and the impact of variants on protein structure and stability. Through extensive hyperparameter tuning of six machine learning algorithms, we found the random forest classifier to be the most effective, yielding an AUROC of 99% on the test set. Var3PPred outperformed three other classifiers, SIFT, PolyPhen, and CADD, on an unseen test set of a SAID-related gene. This demonstrates its capacity for pathogenicity classification of SAID variations. The source code for Var3PPred and the predictions for all 420 missense variants of uncertain significance from the Infevers database are available on GitHub: (https://github.com/alperbulbul1/Var3PPred). creator: Alper Bülbül creator: Emel Timucin creator: Ahmet Can Timuçin creator: Osman Uğur Sezerman creator: Eda Tahir Turanli uri: https://doi.org/10.7717/peerj.17297 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2024 Bülbül et al. title: Similar and divergent responses to salinity stress of jamun (Syzygium cumini L. Skeels) genotypes link: https://peerj.com/articles/17311 last-modified: 2024-05-14 description: BackgroundGenetic variation for salt tolerance remains elusive in jamun (Syzygium cumini).MethodsEffects of gradually increased salinity (2.0–12.0 dS/m) were examined in 20 monoembryonic and 28 polyembryonic genotypes of jamun. Six genotypes were additionally assessed for understanding salt-induced changes in gas exchange attributes and antioxidant enzymes.ResultsSalt-induced reductions in leaf, stem, root and plant dry mass (PDM) were relatively greater in mono- than in poly-embryonic types. Reductions in PDM relative to control implied more adverse impacts of salinity on genotypes CSJ-28, CSJ-31, CSJ-43 and CSJ-47 (mono) and CSJ-1, CSJ-24, CSJ-26 and CSJ-27 (poly). Comparably, some mono- (CSJ-5, CSJ-18) and poly-embryonic (CSJ-7, CSJ-8, CSJ-14, CSJ-19) genotypes exhibited least reductions in PDM following salt treatment. Most polyembryonic genotypes showed lower reductions in root than in shoot mass, indicating that they may be more adept at absorbing water and nutrients when exposed to salt. The majority of genotypes did not exhibit leaf tip burn and marginal scorch despite significant increases in Na+ and Cl−, suggesting that tissue tolerance existed for storing excess Na+ and Cl− in vacuoles. Jamun genotypes were likely more efficient in Cl− exclusion because leaf, stem and root Cl− levels were consistently lower than those of Na+ under salt treatment. Leaf K+ was particularly little affected in genotypes with high leaf Na+. Lack of discernible differences in leaf, stem and root Ca2+ and Mg2+ contents between control and salt treatments was likely due to their preferential uptake. Correlation analysis suggested that Na+ probably had a greater inhibitory effect on biomass in both mono- and poly-embryonic types. Discriminant analysis revealed that while stem and root Cl− probably accounted for shared responses, root Na+, leaf K+ and leaf Cl− explained divergent responses to salt stress of mono- and poly-embryonic types. Genotypes CSJ-18 and CSJ-19 seemed efficient in fending off oxidative damage caused by salt because of their stronger antioxidant defences.ConclusionsPolyembryonic genotypes CSJ-7, CSJ-8, CSJ-14 and CSJ-19, which showed least reductions in biomass even after prolonged exposure to salinity stress, may be used as salt-tolerant rootstocks. The biochemical and molecular underpinnings of tissue tolerance to excess Na+ and Cl− as well as preferential uptake of K+, Ca2+, and Mg2+ need to be elucidated. creator: Anshuman Singh creator: Ashwani Kumar creator: Jai Prakash creator: Arvind Kumar Verma uri: https://doi.org/10.7717/peerj.17311 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2024 Singh et al. title: Vocal complexity in the long calls of Bornean orangutans link: https://peerj.com/articles/17320 last-modified: 2024-05-14 description: Vocal complexity is central to many evolutionary hypotheses about animal communication. Yet, quantifying and comparing complexity remains a challenge, particularly when vocal types are highly graded. Male Bornean orangutans (Pongo pygmaeus wurmbii) produce complex and variable “long call” vocalizations comprising multiple sound types that vary within and among individuals. Previous studies described six distinct call (or pulse) types within these complex vocalizations, but none quantified their discreteness or the ability of human observers to reliably classify them. We studied the long calls of 13 individuals to: (1) evaluate and quantify the reliability of audio-visual classification by three well-trained observers, (2) distinguish among call types using supervised classification and unsupervised clustering, and (3) compare the performance of different feature sets. Using 46 acoustic features, we used machine learning (i.e., support vector machines, affinity propagation, and fuzzy c-means) to identify call types and assess their discreteness. We additionally used Uniform Manifold Approximation and Projection (UMAP) to visualize the separation of pulses using both extracted features and spectrogram representations. Supervised approaches showed low inter-observer reliability and poor classification accuracy, indicating that pulse types were not discrete. We propose an updated pulse classification approach that is highly reproducible across observers and exhibits strong classification accuracy using support vector machines. Although the low number of call types suggests long calls are fairly simple, the continuous gradation of sounds seems to greatly boost the complexity of this system. This work responds to calls for more quantitative research to define call types and quantify gradedness in animal vocal systems and highlights the need for a more comprehensive framework for studying vocal complexity vis-à-vis graded repertoires. creator: Wendy M. Erb creator: Whitney Ross creator: Haley Kazanecki creator: Tatang Mitra Setia creator: Shyam Madhusudhana creator: Dena J. Clink uri: https://doi.org/10.7717/peerj.17320 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2024 Erb et al. title: Hsa_circ_0009096/miR-370-3p modulates hepatic stellate cell proliferation and fibrosis during biliary atresia pathogenesis link: https://peerj.com/articles/17356 last-modified: 2024-05-14 description: BackgroundHepatic stellate cell (HSC) activation and hepatic fibrosis mediated biliary atresia (BA) development, but the underlying molecular mechanisms are poorly understood. This study aimed to investigate the roles of circRNA hsa_circ_0009096 in the regulation of HSC proliferation and hepatic fibrosis.MethodsA cellular hepatic fibrosis model was established by treating LX-2 cells with transforming growth factor β (TGF-β1). RNaseR and actinomycin D assays were performed to detect hsa_circ_0009096 stability. Expression of hsa_circ_0009096, miR-370-3p, and target genes was detected using reverse transcription-qPCR. Direct binding of hsa_circ_0009096 to miR-370-3p was validated using dual luciferase reporter assay. Cell cycle progression and apoptosis of LX-2 cells were assessed using flow cytometry. The alpha-smooth muscle actin (α-SMA), collagen 1A1 (COL1A1), and TGF beta receptor 2 (TGFBR2) protein levels in LX-2 cells were analyzed using immunocytochemistry and western blotting.ResultsHsa_circ_0009096 exhibited more resistance to RNase R and actinomycinD digestion than UTRN mRNA. Hsa_circ_0009096 expression increased significantly in LX-2 cells treated with TGF-β1, accompanied by elevated α-SMA and COL1A1 expression. Hsa_circ_0009096 siRNAs effectively promoted miR-370-3p and suppressed TGFBR2 expression in LX-2 cells, mediated by direct association of hsa_circ_0009096 with miR-370-3p. Hsa_circ_0009096 siRNA interfered with the cell cycle progression, promoted apoptosis, and reduced α-SMA and COL1A1 expression in LX-2 cells treated with TGF-β1. MiR-370-3p inhibitors mitigated the alterations in cell cycle progression, apoptosis, and α-SMA, COL1A1, and TGFBR2 expression in LX-2 cells caused by hsa_circ_0009096 siRNA. In conclusion, hsa_circ_0009096 promoted HSC proliferation and hepatic fibrosis during BA pathogenesis by accelerating TGFBR2 expression by sponging miR-370-3p. creator: Zhouguang Wu creator: Bin Wang creator: Siqi Chen creator: Taoyan Zuo creator: Wenjie Zhang creator: Zhen Cheng creator: Jingru Fu creator: Jiafeng Gong uri: https://doi.org/10.7717/peerj.17356 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2024 Wu et al. title: A comprehensive analysis of the oncogenic and prognostic role of TBC1Ds in human hepatocellular carcinoma link: https://peerj.com/articles/17362 last-modified: 2024-05-14 description: BackgroundsTBC1D family members (TBC1Ds) are a group of proteins that contain the Tre2-Bub2-Cdc16 (TBC) domain. Recent studies have shown that TBC1Ds are involved in tumor growth, but no analysis has been done of expression patterns and prognostic values of TBC1Ds in hepatocellular carcinoma (HCC).MethodsThe expression levels of TBC1Ds were evaluated in HCC using the TIMER, UALCN and Protein Atlas databases. The correlation between the mRNA levels of TBC1Ds and the prognosis of patients with HCC in the GEPIA database was then analyzed. An enrichment analysis then revealed genes that potentially interact with TBC1Ds. The correlation between levels of TBC1Ds and tumor-infiltrating immune cells (TIICs) in HCC were studied using the TIMER 2.0 database. Finally, a series of in vitro assays verified the role of TBC1Ds in HCC progression.ResultsThis study revealed the upregulated expression of TBC1Ds in HCC and the strong positive correlation between the mRNA levels of TBC1Ds and poor prognosis of patients with HCC. The functions of TBC1Ds were mainly related to autophagy and the AMPK pathway. There was also a significant correlation between level of TBC1Ds and tumor-infiltrating immune cells (TIICs) in HCC. The promoting role of TBC1Ds in HCC progression was verified in vitro assays.ConclusionThe results of this analysis indicate that TBC1Ds may serve as new biomarkers for early diagnosis and treatment of HCC. creator: Pei Zhang creator: Lei Zhu creator: Xiaodong Pan uri: https://doi.org/10.7717/peerj.17362 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2024 Zhang et al. title: Arsenic disulfide promoted the demethylation of PTPL1 in diffuse large B cell lymphoma cells link: https://peerj.com/articles/17363 last-modified: 2024-05-14 description: BackgroundPromoter hypermethylation of the tumor suppressor gene is one of the well-studied causes of cancer development. The drugs that reverse the process by driving demethylation could be a candidate for anticancer therapy. This study was designed to investigate the effects of arsenic disulfide on PTPL1 methylation in diffuse large B cell lymphoma (DLBCL).MethodsWe knocked down the expression of PTPL1 in two DLBCL cell lines (i.e., DB and SU-DHL-4 cells) using siRNA. Then the DLBCL proliferation was determined in the presence of PTPL1 knockdown. The methylation of PTPL1 in DLBCL cells was analyzed by methylation specific PCR (MSPCR). The effect of arsenic disulfide on the PTPL1 methylation was determined in DLBCL cell lines in the presence of different concentrations of arsenic disulfide (5 µM, 10 µM and 20 µM), respectively. To investigate the potential mechanism on the arsenic disulfide-mediated methylation, the mRNA expression of DNMT1, DNMT3B and MBD2 was determined.ResultsPTPL1 functioned as a tumor suppressor gene in DLBCL cells, which was featured by the fact that PTPL1 knockdown promoted the proliferation of DLBCL cells. PTPL1 was found hypermethylated in DLBCL cells. Arsenic disulfide promoted the PTPL1 demethylation in a dose-dependent manner, which was related to the inhibition of DNMTs and the increase of MBD2.ConclusionExperimental evidence shows that PTPL1 functions as a tumor suppressor gene in DLBCL progression. PTPL1 hyper-methylation could be reversed by arsenic disulfide in a dose-dependent manner. creator: Chen Chen creator: Ling Wang creator: Yan Liu creator: Shenghong Du creator: Qingliang Teng uri: https://doi.org/10.7717/peerj.17363 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2024 Chen et al. title: Non-destructive prediction of anthocyanin concentration in whole eggplant peel using hyperspectral imaging link: https://peerj.com/articles/17379 last-modified: 2024-05-14 description: Accurately detecting the anthocyanin content in eggplant peel is essential for effective eggplant breeding. The present study aims to present a method that combines hyperspectral imaging with advanced computational analysis to rapidly, non-destructively, and precisely measure anthocyanin content in eggplant fruit. For this purpose, hyperspectral images of the fruits of 20 varieties with diverse colors were collected, and the content of the anthocyanin were detected using high performance liquid chromatography (HPLC) methods. In order to minimize background noise in the hyperspectral images, five preprocessing algorithms were utilized on average reflectance spectra: standard normalized variate (SNV), autoscales (AUT), normalization (NOR), Savitzky–Golay convolutional smoothing (SG), and mean centering (MC). Additionally, the competitive adaptive reweighted sampling (CARS) method was employed to reduce the dimensionality of the high-dimensional hyperspectral data. In order to predict the cyanidin, petunidin, delphinidin, and total anthocyanin content of eggplant fruit, two models were constructed: partial least squares regression (PLSR) and least squares support vector machine (LS-SVM). The HPLC results showed that eggplant peel primarily contains three types of anthocyanins. Furthermore, there were significant differences in the average reflectance rates between 400–750 nm wavelength ranges for different colors of eggplant peel. The prediction model results indicated that the model based on NOR CARS LS-SVM achieved the best performance, with a squared coefficient of determination (R2) greater than 0.98, RMSEP and RMSEC less than 0.03 for cyanidin, petunidin, delphinidin, and total anthocyanin predication. These results suggest that hyperspectral imaging is a rapid and non-destructive technique for assessing the anthocyanin content of eggplant peel. This approach holds promise for facilitating the more effective eggplant breeding. creator: Zhiling Ma creator: Changbin Wei creator: Wenhui Wang creator: Wenqiu Lin creator: Heng Nie creator: Zhe Duan creator: Ke Liu creator: Xi Ou Xiao uri: https://doi.org/10.7717/peerj.17379 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2024 Ma et al. title: Prognostic and chemotherapeutic implications of a novel four-gene pyroptosis model in head and neck squamous cell carcinoma link: https://peerj.com/articles/17296 last-modified: 2024-05-13 description: BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common cancers. Chemotherapy remains one dominant therapeutic strategy, while a substantial proportion of patients may develop chemotherapeutic resistance; therefore, it is particularly significant to identify the patients who could achieve maximum benefits from chemotherapy. Presently, four pyroptosis genes are reported to correlate with the chemotherapeutic response or prognosis of HNSCC, while no study has assessed the combinatorial predicting efficacy of these four genes. Hence, this study aims to evaluate the predictive value of a multi-gene pyroptosis model regarding the prognosis and chemotherapeutic responsiveness in HNSCC.MethodsBy utilizing RNA-sequencing data from The Cancer Genome Atlas database and the Gene Expression Omnibus database, the pyroptosis-related gene score (PRGscore) was computed for each HNSCC sample by performing a Gene Set Variation Analysis (GSVA) based on four genes (Caspase-1, Caspase-3, Gasdermin D, Gasdermin E). The prognostic significance of the PRGscore was assessed through Cox regression and Kaplan–Meier survival analyses. Additionally, chemotherapy sensitivity stratified by high and low PRGscore was examined to determine the potential association between pyroptosis activity and chemosensitivity. Furthermore, chemotherapy sensitivity assays were conducted in HNSCC cell lines in vitro.ResultsAs a result, our study successfully formulated a PRGscore reflective of pyroptotic activity in HNSCC. Higher PRGscore correlates with worse prognosis. However, patients with higher PRGscore were remarkably more responsive to chemotherapy. In agreement, chemotherapy sensitivity tests on HNSCC cell lines indicated a positive association between overall pyroptosis levels and chemosensitivity to cisplatin and 5-fluorouracil; in addition, patients with higher PRGscore may benefit from the immunotherapy. Overall, our study suggests that HNSCC patients with higher PRGscore, though may have a less favorable prognosis, chemotherapy and immunotherapy may exhibit better benefits in this population. creator: Peiyang Yuan creator: Sixin Jiang creator: Qiuhao Wang creator: Yuqi Wu creator: Yuchen Jiang creator: Hao Xu creator: Lu Jiang creator: Xiaobo Luo uri: https://doi.org/10.7717/peerj.17296 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2024 Yuan et al.