Background: Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer. Methods: A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients’ medical record to investigate the association with PD-L1, TILs, and stem cells expressions. Results: We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5. Conclusions: PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.

PURPOSE: Cancer incidence in Saudi Arabia has recently shown an upward trend. Research efforts within the different cancer continuum are pivotal to strengthening control measures. Since cancer research is evolving in the country, it is crucial to understand the current challenges and implement defined interventions to overcome them. The present qualitative study aimed to assess cancer research barriers among researchers and identify potential solutions from their perspectives. METHODS: We conducted a focus group discussion among 17 Saudi-based cancer researchers from diverse research backgrounds, provinces, and institutions. We used descriptive-interpretive thematic analysis following an open-ended approach to investigate the challenges in conducting cancer research. We also captured the solutions suggested based on the researchers' experiences. RESULTS: Six major themes emerged from the analysis: requirements of the data landscape, organizational support, national research roadmap, sustainable funding, clearer policies and regulations, and capacity building. To address challenges in these areas, researchers stressed the need for improved interinstitutional collaborations, immediate availability of research materials, and unlimited and easy access to research data. CONCLUSION: Improving health research is one of the primary goals of Saudi Vision 2030. It is, therefore, essential to overcome the current challenges in cancer research, enabling research findings to inform policies related to cancer control and care provision.

Ovarian germ cell tumors (OVGCTs) account for 28% of all diagnosed ovarian cancers, and malignant germ cell tumors specifically account for approximately 13% of diagnosed ovarian cancers in Saudi Arabia. Although most germ cell tumor patients have a high survival rate, patients who experience tumor recurrence have a poor prognosis and present with more aggressive and chemoresistant tumors. The use of immunotherapeutic agents such as PD-L1/PD-1 inhibitors for OVGCTs remains very limited because few studies have described the immunological characteristics of these tumors. This study is the first to investigate PD-L1 expression in ovarian germ cell tumors and explore the role of PD-L1 expression in tumor microenvironment cells and genetic alterations. A total of 34 ovarian germ cell tumors were collected from pathology archives. The collected tumor tissues included ten dysgerminomas, five yolk sac tumors, five immature teratomas, and one mature teratoma, and the remaining samples were mixed germ cell tumors. The tumors were analyzed using immunohistochemical analysis to determine PD-L1 expression, immune cell infiltration and cancer stem cell populations and their correlation with clinical outcome. Furthermore, the genetic alterations in different subtypes of germ cell tumors were correlated with PD-L1 expression and clinical outcome. Datasets for testicular germ cells (TGCTs) were retrieved from The Cancer Genome Atlas (TCGA) and analyzed using cBioPortal (cbioportal.org) and Gene Expression Profiling Interactive Analysis (GEPIA). Compared with yolk sac tumors, dysgerminomas highly express PD-L1 and are associated with high levels of tumor infiltrating lymphocytes (TILs) and stem cell markers. In addition, compared with PD-L1-negative yolk sac tissue, dysgerminomas/seminomas with high PD-L1 expression are associated with more genetic alterations and a better prognosis. Our findings will contribute to the knowledge about the potential benefits of ovarian cancer immunotherapy in specific subsets of germ cell tumor patients and the risk factors for resistance mediated by tumor microenvironment cells.

Ovarian cancer (OC) remains a major cause of female cancer mortality, with chemoresistance impeding effective treatment. This study investigated the expression of p62/SQSTM1 and Nrf2 in chemoresistant versus chemosensitive OC cell lines and patient tissues. Using quantitative reverse transcription PCR, Western blotting, and immunohistochemistry, we found co-upregulation of p62 and Nrf2 proteins in chemoresistant samples. Proliferation assays revealed that higher p62 expression correlated with reduced cisplatin sensitivity. Sanger sequencing detected synonymous p62 variants in exon 6, with no functional impact. Immunohistochemical scoring showed significantly higher p62 and Nrf2 levels in chemoresistant patients compared to remission and sensitive groups. A strong correlation was observed between p62 expression and cisplatin IC50 values. These findings support the role of the p62/Nrf2 axis in OC chemoresistance and highlight their potential as predictive biomarkers and therapeutic targets. Future studies are warranted to explore targeted interventions that disrupt this pathway to enhance treatment response in OC.

The early variant era of the coronavirus disease 2019 (COVID-19) pandemic was characterized by the emergence of new viral strains and limited vaccination coverage. Data describing the clinical, radiological, and inflammatory characteristics of affected patients in the Middle East remain scarce. This study aimed to fill this gap by comparing the clinical profiles, cytokine responses, and radiological patterns of intensive care unit (ICU) and non-ICU COVID-19 patients during the early phase of the pandemic in Saudi Arabia. A retrospective cohort study was conducted between February and August 2021 across 3 hospitals in the Eastern Province of Saudi Arabia. A total of 117 polymerase chain reaction-confirmed COVID-19 patients were included and categorized into ICU (n = 56) and non-ICU (n = 61) groups. Demographic characteristics, comorbidities, radiological findings, and serum levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-α) were analyzed. Logistic regression identified predictors of ICU admission, while Cox regression evaluated mortality risk factors. ICU patients were older and more symptomatic, particularly with shortness of breath and chest pain. Older age, comorbidities, and elevated IL-8 and TNF-α independently predicted ICU admission, while IL-8 and TNF-α were associated with increased mortality. Amikacin use correlated with higher mortality (hazard ratio: 5.12, P = .015). Radiologically, 86% of ICU patients exhibited bilateral peripheral infiltrates. Distinct inflammatory and radiological profiles characterized severe COVID-19 cases during the early variant era. Routine cytokine profiling at hospital admission may aid clinical triage, while future studies should validate these biomarkers as prognostic tools in pandemic preparedness.

In adult tissues, PAX2 protein is expressed in normal oviductal epithelial cells but not in normal ovarian surface epithelial cells. Studies have reported that PAX2 is expressed in a subset of serous ovarian carcinoma cases but the role of PAX2 in the initiation and progression of ovarian cancer remains unknown. The aim of this study was to understand the biological consequences ofPax2expression in normal and cancerous mouse epithelial (MOSE) cells. We found thatPax2overexpression in both normal and cancerous ovarian epithelial cells induced the formation of vascular channels bothin vitroandin vivo. The results indicate a possible contribution of PAX2 to ovarian cancer progression by increasing the vascular channels to supply nutrients to the tumor cells.