Yan Xing

Improved breast cancer (BC) outcomes highlight the importance of secondary primary cancers (SPCs) on survivor prognosis. The objective of this study was to investigate the potential genetic association between primary BC and ovarian cancer (OC), laying the groundwork for the development of preventive strategies for SPC-OC following BC surgery. This study aimed to assess the connection between BC and OC using a two sample Mendelian randomization (MR) approach, exclusively employing aggregate level data from publicly available genome wide association studies (GWASs). Finally, the Genetic Risk Scores (GRS) method was used for secondary analysis to verify the results robustness further. The IVW method revealed a genetic correlation between Overall BC and ER + BC with Serous borderline tumors, while ER-BC exhibited genetic correlation with Mucinous borderline tumors and high-grade serous ovarian cancer. The findings from the GRS method aligned with those of the primary analysis, reinforcing the study's robustness. Our MR Study identifies an association between BC and OC, highlighting the importance of increased vigilance in clinical practice for individuals with a history of BC. Timely intervention and treatment measures should be taken when necessary.

Aim: The aim of this study was to investigate how the integration status of HPV in the vaginal epithelium affects the development of vaginal intraepithelial neoplasia (VaIN).Methods: Twenty‐four vaginal tissues were collected before applying high‐throughput viral integration detection (HIVID), medical records of them were documented, including age, thin‐prep cytologic test (TCT) and HPV test results, colposcopic biopsy pathology, and other clinical data, such as history of total hysterectomy for cervical lesions, whether they were infected with HPV16/18 with a follow‐up span of 2 years. We summarized the distribution of HPV integration on the host chromosome and HPV type, as well as the hotspot integration gene and its role in the development of VaIN.Results: In this study, 24 cases suffered from VaIN were involved. HPV integration was detected in 11 cases; furthermore, we discovered HPV 16 and 73, chromosome 1 and 2 possessed most HPV integration sites while EMBP1, CLO5A1, EHF, ELF5 as dominate hot spots. Taken clinical outcome into account, we found a significant difference between HPV integration occurrence and VaIN (p = 0.011).Conclusion: (1) This study found a statistical difference between HPV integration and the occurrence of VaIN; (2) HPV integration may provide a new clinical predictor for VaIN and facilitate risk assessment and stratified management of high‐risk patients.

Vaginal intraepithelial neoplasm (VaIN), a precancerous lesion of vaginal cancer, increased distinctly in the past decade, while its occurrence after performing hysterectomy came to attention nowadays. As hr-HPV DNA integrates into host chromosome, transient HPV infection could transform into persistent infection to trigger high-grade intraepithelial neoplasm or HPV-related cancer. High-throughput Viral Integration Detection (HIVID) is a novel genetic sequencing method detecting HPV integration breakpoints for more precise sequence. There is no systematic study on the mechanism and risk assessment prediction system of VaIN in the vaginal stump after total hysterectomy for CIN. In this study, 24 cases suffered from VaIN were involved. HPV integration was detected in 11 cases, furthermore, we discovered HPV 16 and 73, chromosome 1 and 2 possessed most HPV integration sites while EMBP1, CLO5A1, EHF, ELF5 as dominate hot spots. Taken clinical outcome into account, we found a significant difference between HPV integration occurrence and VaIN(p = 0.011). HPV integration could serve as a predictive marker for monitoring and management of VaIN in a way.

Rationale: Hereditary leiomyomatosis and renal cell carcinoma is an uncommon autosomal dominant disease caused by mutations in the fumarate hydratase (FH) gene. They usually demonstrated multiple uterine myomas and preformed surgical procedures for myomectomy and/or hysterectomy 10 years earlier than sporadic myomas due to early development. This case report describes a woman with multiple uterine leiomyomas diagnosed with FH deficiency. Patient concerns: A 37-year-old woman visited a gynecological clinic for the discovery of uterine leiomyoma for more than 1 year. The size of the largest grew from 42 × 27 × 46 to 98 × 85 × 113 mm in 1 year. She had a history of surgery for breast cancer and thyroid cancer but denied a history of uterine leiomyoma in her family. Diagnosis and Interventions: The patient underwent successful transabdominal hysterectomy. The pathological results showed multiple uterine leiomyomas (partly cellular leiomyomas) with scattered large bizarre giant cells. Immunohistochemistry results demonstrated FH deficiency. Outcomes: On follow-up, the patient did not have any complications. She was finally referred to the oncologists and urologists for follow-up. Lessons: Gynecologists should be aware that early onset uterine leiomyoma presenting as large, multiple, and symptomatic lesion, may be associated with FH deficiency.

Background: Globally, ovarian cancer (OC), the deadliest gynecologic malignancy, remains a major cause of mortality, with a rising number of cases in many low- and middle-income countries. Immunotherapy has been proven to be promising for OC. There is increasing awareness of the vital role that tumor mutation burden (TMB) plays in predicting the efficacy of immunotherapy. Women with a family history of OC are at higher risk of the disease due to gene mutations. However, whether these gene mutations are related to immune response and TMB remains to be explored. Methods: Our present work analyzed genetic mutation data of OC patients obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts, and we identified 11 frequently mutated genes, namely, APOB, CSMD3, DST, FAT3, FLG, HMCN1, MUC16, RYR1, TP53, TTN, and USH2A, in accordance with the overlap of two databases. Results: A statistically higher TMB was detected by whole-exome sequencing in patients with OC with CSMD3 mutation than in those with mutations in the other frequently mutated genes. Prognosis analysis performed with patients from the TCGA cohort revealed that those with CSMD3 mutation had an overall survival (OS) that was inferior to that of those with wild-type CSMD3. Gene set enrichment analysis (GSEA) and CIBERSORT analysis indicated that OC samples with CSMD3 mutations had significant involvement of pathways related to the immune response. Conclusion: In summary, we found that CSMD3 mutation is highly correlated with increased TMB and poor clinical prognosis and that it might function as a biomarker for predicting prognosis and choosing an immunotherapy regimen.

Background: recently, many researches have concentrated on the relevance between N1-methyladenosine (m1A) methylation modifications and tumor progression and prognosis. However, it remains unknown whether m1A modification has an effect in the prognosis of ovarian cancer (OC) and its immune infiltration. Methods: Based on 10 m1A modulators, we comprehensively assessed m1A modification patterns in 474 OC patients and linked them to TME immune infiltration characteristics. m1Ascore computed with principal component analysis algorithm was applied to quantify m1A modification pattern in OC patients. m1A regulators protein and mRNA expression were respectively obtained by HPA website and RT-PCR in clinical OC and normal samples. Results: We finally identified three different m1A modification patterns. The immune infiltration features of these m1A modification patterns correspond to three tumor immune phenotypes, including immune-desert, immune-inflamed and immune-excluded phenotypes. The results demonstrate individual tumor m1A modification patterns can predict patient survival, stage and grade. The m1Ascore was calculated to quantify individual OC patient’s m1A modification pattern. A high m1Ascore is usually accompanied by a better survival advantage and a lower mutational load. Research on m1Ascore in the treatment of OC patients showed that patients with high m1Ascore showed marked therapeutic benefits and clinical outcomes in terms of chemotherapy and immunotherapy. Lastly, we obtained four small molecule drugs that may potentially ameliorate prognosis. Conclusion: This research demonstrates that m1A methylation modification makes an essential function in the prognosis of OC and in shaping the immune microenvironment. Comprehensive evaluation of m1A modifications improves our knowledge of immune infiltration profile and provides a more efficient individualized immunotherapy strategy for OC patients.

Uterus Corpus Endometrial cancer (UCEC) is the sixth most common malignant tumor worldwide. In this research, we identified diagnostic and prognostic biomarkers to reflect patients’ immune microenvironment and prognostic. Various data of UCEC patients from the TCGA database were obtained. Firstly, patients were divided into a high tumor mutation burden (TMB) level group and a low TMB level group according to the level of TMB. Then, differentially expressed miRNAs between the two groups were obtained. LASSO logistic regression analysis was used to construct a diagnostic model to predict the level of TMB. Univariate, multivariate, and LASSO regression analysis were used to construct a prognostic risk signature (PRS) to predict the prognosis of UCEC patients. Twenty-one miRNAs were used to construct a diagnostic model for predicting TMB levels. The AUC values of ROC curves for 21-miRNA-based diagnostic models were 0.911 in the training set, 0.827 in the test set, and 0.878 in the entire set. This diagnostic model showed positive correlation with TMB, PDL1 expression, and the infiltration of immune cells. In addition, three prognostic miRNAs were finally used to construct the PRS. The PRS was related to the expression of multiple immune checkpoints and the infiltration of multiple immune cells. Furthermore, the PRS can also reflect the response to some commonly used chemotherapy regimens. We have established a miRNA-based diagnostic model and a prognostic model that can predict the prognosis of UCEC patients and their response to chemotherapy and immunotherapy, thus providing valuable information on the choice of treatment regimen. Graphical Abstract

Female adnexal tumors of probable Wolffian origin (FATWO) are a rare neoplasm from the mesonephric duct remnants with less than 90 cases having been reported worldwide. A 34‐year‐old nulliparous woman was referred to our clinic for a recent discovery of a pelvic mass, the diagnosis of FATWO has been confirmed based on the pathological and immunohistochemical results.