Hasan Çağrı Yıldırım

HERC2 as a Potential Biomarker for Prognosis and Response to Bevacizumab in Ovarian Cancer: A Bioinformatics Approach

It is thought that decreased HERC2 expression increases the sensitivity to ferroptosis in ovarian cancer cells and may increase the VEGF pathway in porcine endothelium by inhibiting LKB1. Based on these data, we aimed to determine whether HERC2 expression may have a positive prognostic significance in patients receiving anti-VEGF based therapy in ovarian cancer patients. The study used public databases and has a retrospective design. Following web tools or datasets were used: TCGA TARGET GTEX study (n = 427 cancer vs. 88 normal ovarian tissue) at UCSC Xena and CPTAC at UALCAN for expression, Kaplan-Meier plotter for overall survival (OS) (n = 1207 for serous histology and n = 37 for endometrioid histology in gene chip), progression-free survival (PFS) (n = 1104 for serous histology in gene chip), TIMER2.0 for correlation of PDCD1, CTLA4, CD274 (PDL1), GEPIA2 for immune gene signatures, OncoLnc, DoSurvive and OncomiR for miRNA and OS associations, CancerSEA for functional status analyses. HERC2 expression levels were lower in ovarian serous cystadenocarcinoma (OV). Lower HERC2 expression was also seen in CPTAC ovarian cancer cohort. In the overall ovarian cancer cohort, decreased HERC2 expression was associated with longer OS. In the serous histology cohort, decreased HERC2 expression was associated with shorter PFS in those receiving bevacizumab-containing chemotherapy. PDL1 and HERC2 expressions were positively correlated. hsa-miR-500a-3p was negatively correlated with HERC2 in OV, and increased expression of this miRNA was associated with better OS. There was a positive association between HERC2 expression and angiogenesis and EMT, and a negative association with invasion. Decreased HERC2 expression is associated with a favorable prognosis in overall ovarian cancer cohort, but is associated with a worse PFS in patients receiving bevacizumab with serous ovarian cancer.

Effect of hypoxia-inducible factor-1 alpha expression on survival in patients with metastatic cervical squamous cell carcinoma treated with first-line chemotherapy and bevacizumab

This study addresses the gap in understanding the prognostic relevance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in metastatic cervical squamous cell carcinoma (SCC) patients undergoing anti-vascular endothelial growth factor (VEGF)-based therapy. A retrospective multicenter study (n = 34) explored HIF-1 alpha expression via immunohistochemistry in patients treated with platinum chemotherapy and bevacizumab. Median progression-free survival (PFS) was significantly lower in the HIF-1 alpha low score group compared to the high score group (4.9 vs 12.9 months, P = 0.014). Similarly, the median overall survival (OS) was significantly reduced in the HIF-1 alpha low score group (8.3 vs 20.4 months, P = 0.006). This study, the first of its kind, highlights the prognostic significance of HIF-1 alpha expression in metastatic cervical SCC patients treated with bevacizumab-based therapy.

KELIM Score Predicts Outcome in Patients with Platinum-Resistant/Refractory Recurrent Ovarian Cancer

Efficacy of cumulative cisplatin dose on survival in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy: multicenter study by Turkish Oncology Group

To investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy. A retrospective analysis was conducted on 654 patients with stage IB3-IVA disease treated with definitive chemoradiotherapy. Radiotherapy was applied as external beam pelvic with or without para-aortic radiotherapy and brachytherapy. Concomitant chemotherapy was in the form of weekly or 3 weekly cisplatin. Data on demographics, treatment protocols, cumulative cisplatin dose, adverse effects, and survival outcomes were collected. Statistical analyses, including univariate and multivariate Cox regression models, were used to assess factors influencing progression free survival and overall survival. The median cumulative cisplatin dose was 210 mg (range 40-320), and ≥200 mg in 503 (76.9%) patients. Median follow-up was 35 months (range 1-150). The 5 year progression free survival and overall survival rates were 66.9% and 77.1%, respectively. Multivariate analysis identified poor performance status, non-squamous cell histology, presence of lymph node metastases, and hemoglobin 200 mg, particularly in patients with lymph node metastases, significantly improved overall survival. Factors such as anemia, toxicity related challenges, and comorbidities were identified as critical considerations in treatment planning. These findings emphasize the balance between maximizing therapeutic efficacy and managing toxicity, guiding personalized treatment approaches for locally advanced cervical cancer.