Jingxin Ding

Single-cell RNA sequencing reveals tumor heterogeneity in small cell neuroendocrine cervical carcinoma

Small cell neuroendocrine cervical carcinoma (SCNECC) is an aggressive gynecological malignancy with poor prognosis. The precision therapeutic strategies for SCNECC are severely limited by the complex tumor microenvironment. Here, we mapped the single-cell landscape of a total of six samples from matched SCNECC cancerous foci and normal adjacent cervical tissues. Through analysis of 68,455 high-quality cells, malignant epithelial cells were identified with increased neuroendocrine differentiation and reduced keratinization. Within four epithelial cell clusters, the key transcription factors ASCL1, NEUROD1, POU2F3, and YAP1 defined molecular subtypes. Transitional trajectory among subtypes characterized two distinct carcinogenesis pathways in SCNECC. The P-type SCNECC showed potentially enhanced immune infiltration over other subtypes. Intercellular communication analysis identified several immune checkpoints and differentially expressed signaling pathways among subtypes. Through western blotting, the TC-YIK cell line was identified as an N-type SCNECC cell with high expression of SLFN11 and mTOR. Based on immunohistochemical staining of malignant subtyping markers, a cohort of 66 SCNECC patients from our hospital were divided into five subtypes. We further combined YAP1 expression with other clinicopathological factors (Cox p < 0.05) to establish a prognostic nomogram. Overall, these findings provide clues for tumorigenesis, precision treatments and prognostic prediction in SCNECC.

Prognosis and factors affecting colorectal cancer with ovarian metastasis

Colorectal cancer is one of the most common malignant tumors. Its incidence has been increasing in recent years, as has the number of cases of ovarian metastasis of colorectal cancer. The prognosis of colorectal cancer with ovarian metastasis is poor, and it is an important cause of death in female patients. A variety of clinicopathological factors were found to be related to the prognosis of patients with colorectal cancer with ovarian metastasis, such as menopausal status, metastasis limited to the pelvis, and tumor differentiation. Tumor genetic characteristics also provide a new perspective for the prognostic evaluation of colorectal cancer with ovarian metastasis. The prognosis of ovarian metastasis is also closely associated with treatment. The major treatment methods are prophylactic oophorectomy, surgical resection of the primary and metastatic lesions, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and systematic therapy. If feasible, complete surgical resection of the primary and ovarian metastatic macroscopic lesions combined with postoperative chemotherapy might currently be the most effective treatment for improving the prognosis of patients with colorectal cancer with ovarian metastasis. Genetic analysis also provides a theoretical basis for potential targeted therapy and immunotherapy.

Vaginal Microbial Environment Skews Macrophage Polarization and Contributes to Cervical Cancer Development

As a common female reproductive system malignancy, cervical cancer (CC) disturbs numerous women’s health. This study demonstrates the role of the vaginal microbial environment (Peptostreptococcus anaerobius) in cervical cancer. Functional assays, including cell proliferation assay, tube formation assay, and immunofluorescence staining, revealed the effect of Peptostreptococcus anaerobius-treated macrophages on cell proliferation and the angiogenesis process. The tube formation assay disclosed the function of Peptostreptococcus anaerobius-treated macrophages on angiogenesis. In vivo assays were also established to explore the impact of Peptostreptococcus anaerobius-treated macrophages on tumor migration. The results revealed that Peptostreptococcus anaerobius-induced macrophages boosted cervical cancer migration and angiogenesis both in vitro and in vivo. Then, this study unveiled that Peptostreptococcus anaerobius-induced macrophage secreted VEGF to stimulate the angiogenesis in cervical cancer. As a whole, Peptostreptococcus anaerobius-induced macrophage facilitates cervical cancer development through modulation of VEGF expression.

Ubiquitin C-terminal hydrolase L1 promotes lymph node metastasis in small cell neuroendocrine carcinomas of the cervix

Objective To screen for specific differentially expressed genes in small cell neuroendocrine carcinoma of the cervix (SCNEC) and to further explore their roles and mechanisms in tumor progression. Methods Differentially expressed genes in SCNEC compared with squamous cell carcinoma (SCC) and adenocarcinoma (AC) were screened by microarray and immunohistochemical analyses. The biological functions of the identified genes were examined in a SCNEC cell line using RNA interference and over-expression plasmid-transfection technologies. Co-expression network analysis and immunoprecipitation technology were used to explore the potential mechanisms. Results Compared with SCC and AC, UCHL1 (encoding ubiquitin C-terminal hydrolase L1) was identified as a specific differentially expressed gene in SCNEC, which was positively related to lymph node metastasis (LNM). Migration and invasion of SCNEC tumor cells were induced by UCHL1 over-expression and suppressed by UCHL1 down-regulation, as shown by scratch and transwell invasion assays. Co-expression network analysis suggested that Prospero homeobox protein 1 (PROX1) might interact with UCHL1, and in vivo immunoprecipitation and western blots verified that levels of ubiquitinated PROX1 were significantly decreased following UCHL1 overexpression. Conclusion UCHL1 is a potential biomarker of LNM in SCNEC. UCHL1 might promote SCNEC cell migration and invasion by reducing PROX1 ubiquitination.

Anoikis Patterns in Cervical Cancer: Identification of Subgroups and Construction of a Novel Risk Model for Predicting Prognosis and Immune Response

Background: Cervical cancer has high morbidity and intratumor heterogeneity. Anoikis, a form of programmed cell death preventing detached cancer cells from readhering, may serve as a potential prognostic signature for cervical cancer. This study aimed to assess the predictive performance of anoikis patterns in cervical cancer prognosis. Methods: Differentially expressed anoikis-related genes (DEARGs) were identified between normal and cancer samples using data from the Gene Expression Omnibus database with the elucidation of mutation status and bio-function. Novel anoikis molecular subtypes were defined in The Cancer Genome Atlas (TCGA) cohort with consensus clustering analysis. A multigene prognostic signature was constructed through least absolute shrinkage and selection operator (LASSO) Cox analysis with internal and external validation. The nomogram-based survival probability of cervical cancer over 3 and 5 years was predicted and assessed with calibration, receiver operating characteristic, decision curve analysis, and Kaplan-Meier curves. Additionally, mutation, function, and immune analysis were conducted among different risk groups. Results: We identified 77 DEARGs between normal and cervical cancer tissues and explored their mutation status and functions. The TCGA cohort could be categorized into two subtypes based on these genes. Furthermore, seven prognostic signature genes were constructed, and the nomogram involving DEARGs and clinicopathological characteristics showed satisfactory predictive performance. Functional analysis indicated that immune-related genes were enriched, and immune status, as well as sensitivity of chemotherapies and targeting drugs, were correlated with the risk model. Conclusions: Anoikis patterns play important roles in tumor immunity and can be used to predict the prognosis of cervical cancers.