Background: Although research on the effects of comorbidities on coronavirus disease 2019 (COVID-19) patients is increasing, the risk of cancer history has not been evaluated for the mortality of patients with COVID-19. Methods: In this retrospective study, we included 3232 patients with pathogen-confirmed COVID-19 who were hospitalized between January 18th and March 27th, 2020, at Tongji Hospital in Wuhan, China. Propensity score matching was used to minimize selection bias. Results: In total, 2665 patients with complete clinical outcomes were analyzed. The impacts of age, sex, and comorbidities were evaluated separately using binary logistic regression analysis. The results showed that age, sex, and cancer history are independent risk factors for mortality in hospitalized COVID-19 patients. COVID-19 patients with cancer exhibited a significant increase in mortality rate (29.4% vs. 10.2%, P < 0.0001). Furthermore, the clinical outcomes of patients with hematological malignancies were worse, with a mortality rate twice that of patients with solid tumors (50% vs. 26.1%). Importantly, cancer patients with complications had a significantly higher risk of poor outcomes. One hundred nine cancer patients were matched to noncancer controls in a 1:3 ratio by propensity score matching. After propensity score matching, the cancer patients still had a higher risk of mortality than the matched noncancer patients (odds ratio (OR) 2.98, 95% confidence interval (95% CI) 1.76-5.06). Additionally, elevations in ferritin, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, procalcitonin, prothrombin time, interleukin-2 (IL-2) receptor, and interleukin-6 (IL-6) were observed in cancer patients.

Among all malignant tumors that threaten human health, virus-related tumors account for a large proportion. The treatment of these tumors is still an urgent problem to be resolved. The immune system is the “guard” of the human body, resisting the invasion of foreign substances such as viruses. Studies have shown that immunotherapy has clinical significance in the treatment of a variety of tumors. In particular, the emergence of immune checkpoint inhibitors (ICIs) in recent years has opened a new door to cancer therapy. Considering the potential role of ICIs in the treatment of virus-related cancers, we focused on their therapeutic effect in virus-associated cancers and explored whether the therapeutic effect in virus-associated cancers was related to virus infection status. Although there is no clear statistical significance indicates that ICIs are more effective in virus-associated cancers than non-virus infections, the efficacy of checkpoint inhibitors in the treatment of virus-related cancers is promising. We believe that this research provides a good direction for the implementation of individualized precision medicine.

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As molecular analyses based on high-throughput sequencing have developed, the molecular classification of cancer has facilitated clinical work. The aim of the present study was to identify a new potential therapeutic target for cervical carcinoma by molecular analyses. We firstly tested the LOXL2 expression pattern in 50 paired normal cervix and cervical carcinoma via qPCR and immunohistochemistry, and the LOXL2 expression pattern was found to be in accordance with public datasets from Gene Expression Omnibus (GEO). Then, we comprehensively rewired the 176 cervical carcinoma samples from The Cancer Genome Atlas (TCGA), subsequently clustered the samples into two groups corresponding to LOXL2 expression to determined the associations between LOXL2 expression status and molecular characterizations of cervical carcinoma. In vitro assays for further verifying the correlations in SiHa-shLOXL2 and HeLa-shLOXL2 cell lines. In this study, we found that LOXL2 highly expressed in carcinoma tissue, with 14 CpG islands of LOXL2 promoter that were significantly and negatively associated with its expression in cervical carcinoma. And there were notable correlations among LOXL2 expression status and molecular characterizations of cervical carcinoma, including diagnostic age, HPV A7 types, mRNA molecular clusters, miRNA molecular clusters, and DNA methylation molecular clusters et al. In addition, high LOXL2 expression was negatively correlated with lower tumor mutation density, especially in EP300, ERBB2, EGFR and NOTCH2, and was negatively correlated with lower expression of APOBEC3 family genes, such as APOBEC3A, APOBEC3B, APOBEC3D, and APOBEC3G. Furthermore, high LOXL2 expression was associated with poor overall (OS) and poor disease-free survival (DFS) in cervical carcinoma, and was associated with higher epithelial-mesenchymal transition (EMT) score, enrichment of extracellular matrix (ECM) signaling, the phenotype that was found to be associated with poor prognosis Cao et al. LOXL2 With EMT in Cervical Carcinoma in cervical carcinoma from TCGA. Conversely, the ability of cell proliferation and cell migration were reversed in LOXL2 knock-down cervical cell lines via regulating the genes' expression of EMT phenotype in vitro. Overall, we demonstrated the correlation between LOXL2 expression status and cancer molecular characterizations of cervical carcinoma, and identified LOXL2 may serve as a therapeutic target for such carcinoma.

The effective treatment of advanced cervical cancer remains challenging. Herein, single-nucleus RNA sequencing (snRNA-seq) and SpaTial enhanced resolution omics-sequencing (Stereo-seq) are used to investigate the immunological microenvironment of cervical squamous cell carcinoma (CSCC). The expression levels of most immune suppressive genes in the tumor and inflammation areas of CSCC are not significantly higher than those in the non-cancer samples, except for LGALS9 and IDO1. Stronger signals of CD56 + NK cells and immature dendritic cells are found in the hypermetabolic tumor areas, whereas more eosinophils, immature B cells, and Treg cells are found in the hypometabolic tumor areas. Moreover, a cluster of pro-tumorigenic cancer-associated myofibroblasts (myCAFs) are identified. The myCAFs may support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling of the tumor extracellular matrix. Furthermore, these myCAFs are associated with poorer survival probability in patients with CSCC, predict resistance to immunotherapy, and might be present in a small fraction (< 30%) of patients with advanced cancer. Immunohistochemistry and multiplex immunofluorescence staining are conducted to validate the spatial distribution and potential function of myCAFs. Collectively, these findings enhance the understanding of the immunological microenvironment of CSCC and shed light on the treatment of advanced CSCC.

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Human papillomavirus (HPV) integration and high expression of HPV oncogenes (E6 and E7) are important mechanisms for HPV carcinogenesis in cervical cancer. However, the relationship between HPV integration and HPV E6 spliced transcripts, as well as the underlying mechanisms of HPV integration in carcinogenesis after HPV E6 splicing remains unclear. We analyzed HPV‐coiled‐coil domain containing 106 (CCDC106) integration samples to characterize the roles of HPV integration, E6 spliceosome I (E6*I), and high CCDC106 expression in cervical carcinogenesis. We found that E6 was alternatively spliced into the E6*I transcript in HPV‐CCDC016 integration samples with low p53 expression, in contrast to the role of E6*I in preventing p53 degradation in cervical cancer cells. In addition, CCDC106 was highly expressed after HPV‐CCDC106 integration, and interacted with p53, resulting in p53 degradation and cervical cancer cell progression in vitro and in vivo. Importantly, when E6*I was highly expressed in cervical cancer cells, overexpression of CCDC106 independently degraded p53 and promoted cervical cancer cell progression. In this study, we explored the underlying mechanisms of HPV‐CCDC106 integration in HPV carcinogenesis after HPV E6 splicing, which should provide insight into host genome dysregulation in cervical carcinogenesis.

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