Impact of p53, HIF1a, Ki-67, CA-9, and GLUT1 Expression on Treatment Outcomes in Locally Advanced Cervical Cancer Patients Treated With Definitive Chemoradiation Therapy

Abstract

Purpose/Objective: The objective of this study was to assess the association between pretreatment p53, hypoxia inducible factor 1a (HIF1a), Ki-67, carbonic anhydrase-9 (CA-9), and glucose transporter 1 (GLUT1) expression in locally advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), local-regional control (LC), and distant metastases–free survival (DMFS). Patients and Methods: Twenty-eight patients treated definitively and consecutively for cervical cancer with CRT had p53, HIF1a, Ki-67, CA-9, and GLUT1 protein expression assessed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes. Outcomes were stratified by p53 (H-score: <15 vs. ≥15), HIF1a (H-score: <95 vs. ≥95), Ki-67 (labeling index <41% vs. ≥41%), CA-9 (H-score: <15 vs. ≥15), and GLUT1 (H-score: <175 vs. ≥175) expression. OS, PFS, LC, and DMFS rates were calculated using the Kaplan-Meier method, and differences between groups were evaluated by the log-rank test. Results: Notable clinical characteristics of the cohort included median age of 51 years (range: 32 to 74 y), FIGO stage IIB disease (57.2%), clinical node-negative disease (64.3%), squamous cell carcinoma (89.3%), and adenocarcinoma (10.7%). Treatment outcomes included 5-year OS (57.2%), PFS (48.1%), LC (72.1%), and DMFS (62.9%). For HIF1a H-score <95 and ≥95, the 5-year OS (52.0% and 68.4%, P=0.58), PFS (53.0% and 40.9%, P=0.75), LC (71.6% and 68.2%, P=0.92), and DMFS (59.7% and 52.0%, P=0.91) were not significantly different. For Ki-67 labeling index <41% and ≥41%, the 5-year OS (44.9% and 66.6%, P=0.35), PFS (38.9% and 55.4%, P=0.53), LC (57.7% and 85.7%, P=0.22), and DMFS (67.3% and 61.0%, P=0.94) were not significantly different. For CA-9 H-score <15 and ≥15, the 5-year OS (54.4% and 66.7%, P=0.39), PFS (57.3% and 40.0%, P=0.87), LC (70.0% and 70.0%, P=0.95), and DMFS (70.0% and 46.7%, P=0.94) were not significantly different. For GLUT1 H-score <175 and ≥175, the 5-year OS (43.6% and 43.6%, P=0.32), PFS (55.6% and 49.5%, P=0.72), LC (72.9% and 71.5%, P=0.97), and DMFS (62.5% and 59.6%, P=0.76) were not significantly different. For p53, H-score <15 and ≥15, the 5-year OS (62% and 53%), PFS (63% and 30.3%), LC (87.5% and 52%), and DMFS (79.6% and 41.6%). Conclusions: In this study population, HIF1a, Ki-67, CA-9, and GLUT1 expression did not predict treatment response or outcomes in locally advanced cervical cancer patients treated definitively with CRT. There was a nonstatistically significant trend towards worse outcomes with p53 expression.

Hypoxia‐induced tumor exosomes promote angiogenesis through miR‐1825/TSC2/mTOR axis in oral squamous cell carcinoma

“…To confirm the induction of hypoxia, we examined the relative expressions of the hypoxia markers at the mRNA (HIF1α, HIF2α, and CA-9) and protein (HIF1α) levels in FaDu and SCC-9 cells treated with aforementioned doses of CoCl 2 . In line with the literature findings [37][38][39] we found HIF1α and HIF2α levels as decreased and CA-9 level as increased at mRNA level in hypoxia-induced cells as compared to control normoxic cells (Figure 1C,D). As expected, CoCl 2 treatment significantly induced HIF1α protein level in both FaDu and SCC-9 cells under hypoxic conditions (Figure 1E), which pointed successful establishment of hypoxia model in OSCC cells via treatment of CoCl 2 .…”

Camrelizumab for the treatment of advanced cervical adenocarcinoma: a case report and literature review

“…Piha-Paul and Biton et al (3,13) reported that mutations of this gene in lung adenocarcinoma were strongly associated with good efficacy of PD-1 inhibitors, while the effects were opposite in ovarian, esophageal, and colon cancers. No clinical study has confirmed the effect in cervical cancer, but basic research by Tornesello et al (14) showed that TP53 plays an essential role in cervical adenocarcinoma, and high expression of this gene is also considered a predictor of poor prognosis in cervical cancer (15). produce more cancer-related antigens and are susceptible to the immune system (17).…”

Sanguinarine Reverses Pulmonary Vascular Remolding of Hypoxia-Induced PH via Survivin/HIF1α-Attenuating Kv Channels

“…Effects of Sanguinarine on HIF1α-Survivin/ TGFb/Smad Pathways HIF1α is one of the critical mediators in hypoxia-induced injury either by regulating proliferation and apoptosis, oxygen stress-related genes such as SMAD and survivin or interacting with other transcription factors such as p53. Thus, inhibiting the HIF1α pathway has been believed to be a potential therapy for cancer, as well as for hypoxia-induced diseases (Su et al, 2019;Gaber et al, 2021). Accordingly, in this study, we examined whether the inhibiting effects of sanguinarine on hypoxiainduced PASMC proliferation and fibrosis were mediated by the HIF1α/TGFβ/Smad pathway or/and by its feed-forward loop with survivin.…”