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Abstract Background Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. Disulfidptosis is a recently identified mechanism of programmed cell death that occurs in SLC7A11 high-expressing cells due to glucose starvation-induced disintegration of the cellular disulfide skeleton. We aimed to explore the potential of disulfidptosis, as a prognostic and therapeutic marker in HCC. Methods We classified HCC patients into two disulfidptosis subtypes (C1 and C2) based on the transcriptional profiles of 31 disulfrgs using a non-negative matrix factorization (NMF) algorithm. Further, five genes (NEIL3, MMP1, STC2, ADH4 and CFHR3) were screened by Cox regression analysis and machine learning algorithm to construct a disulfidptosis scoring system (disulfS). Cell proliferation assay, F-actin staining and PBMC co-culture model were used to validate that disulfidptosis occurs in HCC and correlates with immunotherapy response. Results Our results suggests that the low disulfidptosis subtype (C2) demonstrated better overall survival (OS) and progression-free survival (PFS) prognosis, along with lower levels of immunosuppressive cell infiltration and activation of the glycine/serine/threonine metabolic pathway. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. As a total survival risk factor, disulfS demonstrated high predictive efficacy in multiple validation cohorts. We demonstrated the presence of disulfidptosis in HCC cells and its possible relevance to immunotherapeutic sensitization. Conclusion The present study indicates that novel biomarkers related to disulfidptosis may serve as useful clinical diagnostic indicators for liver cancer, enabling the prediction of prognosis and identification of potential treatment targets. Graphical Abstract

Abstract Background Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with high incidence and poor prognosis. Although immunotherapy has brought significant survival benefits to advanced UCEC patients, traditional evaluation indicators cannot accurately identify all potential beneficiaries of immunotherapy. Consequently, it is necessary to construct a new scoring system to predict patient prognosis and responsiveness of immunotherapy. Methods CIBERSORT combined with weighted gene co-expression network analysis (WGCNA), non-negative matrix factorization (NMF), and random forest algorithms to screen the module associated with CD8+ T cells, and key genes related to prognosis were selected out by univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to develop the novel immune risk score (NIRS). Kaplan–Meier (K-M) analysis was used to compare the difference of survival between high- and low- NIRS groups. We also explored the correlations between NIRS, immune infiltration and immunotherapy, and three external validation sets were used to verify the predictive performance of NIRS. Furthermore, clinical subgroup analysis, mutation analysis, differential expression of immune checkpoints, and drug sensitivity analysis were performed to generate individualized treatments for patients with different risk scores. Finally, gene set variation analysis (GSVA) was conducted to explore the biological functions of NIRS, and qRT-PCR was applied to verify the differential expressions of three trait genes at cellular and tissue levels. Results Among the modules clustered by WGCNA, the magenta module was most positively associated with CD8+ T cells. Three genes (CTSW, CD3D and CD48) were selected to construct NIRS after multiple screening procedures. NIRS was confirmed as an independent prognostic factor of UCEC, and patients with high NIRS had significantly worse prognosis compared to those with low NIRS. The high NIRS group showed lower levels of infiltrated immune cells, gene mutations, and expression of multiple immune checkpoints, indicating reduced sensitivity to immunotherapy. Three module genes were identified as protective factors positively correlated with the level of CD8+ T cells. Conclusions In this study, we constructed NIRS as a novel predictive signature of UCEC. NIRS not only differentiates patients with distinct prognoses and immune responsiveness, but also guides their therapeutic regimens.

BackgroundThe main factors responsible for low-grade glioma (LGG)s’ poor prognosis and treatment effectiveness include recurrence and malignant progression. A specific type of programmed cell death, known as anoikis, which is crucial for tumor invasion and metastasis, however, has not yet been investigated in LGGs.MethodsWe downloaded data of 509 samples from the TCGA-LGG cohort, carried out cluster analysis for typing twice on the basis of 19 anoikis-associated genes, and the subtypes were evaluated the differences in clinicopathological and biological features. ESTIMATE and single-sample gene set enrichment analysis were employed to examine the immunological milieu of LGGs, and enrichment analysis was used to look into the underlying biological mechanisms in LGGs. Cox regression analysis and the Least Absolute Shrinkage and Selection Operator regression algorithm were used to create a prediction scoring system. The scoring system was used for classifying LGG into high- and low- anoikis riskscore (anoiS) groups. The impact of the anoiS on the prognosis, standard treatment, and immunotherapy of patients with LGG was assessed using survival analysis and drug sensitivity analysis. Cell experiments were employed for the verification of the differential expression between LGG cells and normal cells of the anoikis gene team that regard CCT5 as the core.ResultsBased on the expression profiles of the 19 anoikis-associated genes, all individuals with LGG were classified into four subtypes and two macrosubtypes. The different macrosubtypes had significantly different biological characteristics, and the anoirgclusterBD subtype manifested a significantly bad prognosis and a high immune level of infiltration. And subsequent secondary genotyping also showed good prognostic discrimination. We further constructed an anoikis scoring system, anoiS. LGG patients having a high anoiS had a worse prognosis in comparison to those having a low anoiS. The high anoiS group exhibited larger levels of immune infiltration and superior immunotherapy efficacy than the low anoiS group. The high anoiS group was also more susceptible to temozolomide (TMZ) than the low anoiS group, according to a drug sensitivity analysis of TMZ.ConclusionThis study constructed a scoring system for predicting the prognosis of patients with LGG and their responsive to TMZ and immunotherapy.

Uterine surgery is a common predisposing factor for uterine rupture, while an invasive mole that leads to uterine rupture is a rare clinical occurrence. Here, we report a case of a 31-year-old childless woman who underwent abortion after 53 days of pregnancy. She still experienced abdominal pain and scanty vaginal bleeding after the abortion. Her levels of human chorionic gonadotropin (HCG) were high, while ultrasound and MRI results revealed an enlarged uterus and a mass in the myometrium. During preparation for treatment, the gynecologist ruptured the uterus of the patient, leaving her shocked. Eventually the patient's uterus was removed the uterus and pathologically diagnosed as result is the an invasive mole.

Background/aim: This study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of cancer-related genes and the risk of multiple primary malignancies involving colorectal cancer. Materials and methods: We collected tissue samples from 22 multiple primary cancer patients with primary colorectal cancer and performed genotyping assay for 116 SNP loci from 62 genes encoding peptides functioning in various signaling pathways using the DNA MassARRAY system. The chi-square test was used to compare the differences in base frequencies between patients and a control Chinese population from HapMap through the NCBI database. Results: No significant differences in frequencies were detected for 81 SNPs (P > 0.05), while serious frequency differences were observed for 35 SNPs from 31 genes (P < 0.05), which included ERCC6 (rs2228526), ERCC1 (rs3212986), CASP8 (rs3834129, rs3769818), and others presented. Five of these SNPs were previously reported to be associated with the pathogenesis of colorectal cancer. Conclusion: The 35 SNPs from 31 genes may be associated with the risk of multiple primary malignancies involving colorectal cancer. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the occurrence and clinical features of cases of multiple primary cancers including colorectal cancer (MPCC). The medical records of patients with colorectal cancer (CRC) who underwent surgery at the Third Xiangya Hospital of Central South University (Changsha, China) between August 2007 and August 2014 were retrospectively analyzed. Patients with MPCCs were identified and mutation analyses were performed on colon specimens. The results revealed that among 1,311 patients with CRC, 59 had MPCC (including 35 cases of =1 CRC with =1 other cancer type, and 24 cases with multiple CRCs and no other primary cancers). Foci occurred on the right side of the colon (n=32), in the rectum (n=28), and on the left side of the colon (n=24). MPCCs were synchronous in 24 patients, metachronous in 32 patients, and both in 3 patients. Age of onset and presence of polyps were identified as significantly different between MPCC and CRC overall (P<0.05); however, sex or adenoma incidence were not observed to differ significantly between groups. Mutation incidence rates in 26 specimens were 11.54% for KRAS proto-oncogene GTPase (KRAS) G13D, 3.85% for KRAS Q61R and 3.85% B-Raf proto-oncogene serine/threonine kinase V600E. Mutations of exon 21 of the epithelial growth factor receptor gene, including L858R and L861Q, and of KRAS G12V were not detected. In conclusion, the likelihood of occurrence of MPCC is closely associated with the age of onset and the presence of polyp(s). Routine examination of multiple systems is necessary for patients with CRC to avoid missed diagnosis and misdiagnosis. Further study is required to demonstrate the molecular mechanism of CRC in cases of multiple primary cancers. [ABSTRACT FROM AUTHOR]