Association of a Combined Cancer Exhaustion Score with Circulating Tumor Cells and Outcome in Ovarian Cancer—A Study of the OVCAD Consortium

We investigated the prognostic role of systemic characteristics for cancer exhaustion and the presence of circulating tumor cells (CTCs) in primary epithelial ovarian cancer (EOC) patients. We included 185 patients in this multicenter study with a median follow-up time of 10.25 years. Albumin, c-reactive protein (CRP) and the kynurenine to tryptophan ratio (Kyn/Trp) as well as the CTC-related marker cyclophilin C (PPIC) were obtained before primary therapy and were correlated to the respective clinical and outcome data. The information provided by albumin and Kyn/Trp was integrated in a combined score for cancer exhaustion (CCES). A high CCES characterized by hypoalbuminemia and a high Kyn/Trp was associated with both decreased overall and progression-free survival, independent from other known prognostic factors in a multivariable analysis. The presence of PPIC-positive CTCs was significantly associated with a high CCES, highlighting that the interplay between the systemic microenvironment and CTCs should be considered in “liquid biopsy” biomarker assessment.

Chondroitin Sulfate Disaccharides, a Serum Marker for Primary Serous Epithelial Ovarian Cancer

Glycosaminoglycans are long polysaccharidic chains, which are mostly present in connective tissues. Modified GAG expression in tissues surrounding malignant cells has been shown to contribute to tumor progression, aggressive status and metastasis in many types of cancer. Ovarian cancer is one of the most lethal gynecological malignancies due to its late diagnosis because of the absence of clear symptoms and unavailability of early disease markers. We investigated for the first time GAG changes at the molecular level as a novel biomarker for primary epithelial ovarian cancer. To this end, serum of a cohort of 68 samples was digested with chondroitinase ABC, which releases chondroitin sulfate into disaccharides. After labeling and purification, they were measured by HPLC, yielding a profile of eight disaccharides. We proposed a novel GAG-based score named “CS- bio” from the measured abundance of disaccharides present that were of statistical relevance. CS-bio’s performance was compared with CA125, the clinically used serum tumor marker in routine diagnostics. CS-bio had a better sensitivity and specificity than CA125. It was more apt in differentiating early-stage patients from healthy controls, which is of high interest for oncologists.

Correlation of Molecular Tumor Markers CA125, HE4, and CEA with the Development and Progression of Epithelial Ovarian Cancer

Background: This study was designed to explore the levels of serum moleculartumor markers carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), and carcinoembryonic antigen (CEA) in patients with primary epithelial ovarian cancer, and their correlation with the progression of the cancer. Methods: A total of 222 people were enrolled in this study admitted to Jining Maternal and Child Health and Family Planning Service Center from January 2016 to December 2017. There were 122 patients with primary epithelial ovarian cancer (ovarian cancer group), 50 patients with benign ovarian diseases (benign control group), and 50 healthy individuals (normal control group). The levels of serum CA125, CEA, and HE4 were detected by the electrochemical luminescence method and ELISA. Results: The levels of serum CA125, HE4, and CEA in the ovarian cancer group were significantly higher than those in patients with the benign control group and the normal control group (P<0.01). The levels of serum CA125, HE4, and CEA in the high clinical staging group (stage III and stage II), low differentiation group, comorbid ascites group, metastasis group, and recurrence group were significantly higher than those in the low clinical staging group (stage I and stage II), high + moderate differentiation group, non-ascites group, non-metastasis group, and non-recurrence group, respectively (all P<0.05), and the levels of serum CA125, HE4, and CEA decreased significantly after treatment (P<0.01). Conclusion: The levels of serum CA125, HE4, and CEA are closely related to the development and progression of epithelial ovarian cancer, and combined detection of CA125, HE4 and CEA is of great significance for early diagnosis, disease development monitoring, and prognosis evaluation of epithelial ovarian cancer.

Differential expression of PD-L1 between primary and metastatic epithelial ovarian cancer and its clinico-pathological correlation

Ovarian cancer (OC) is one of the most common gynecologic cancer, which has the worst prognosis and highest mortality rate. The lack of curative treatment and the high relapse rate, especially in advanced OC, continues to present a clinical challenge, highlighting the need for new therapeutic strategies. This study was performed to compare the expression of PD-L1 in primary epithelial ovarian cancer (EOC) and their corresponding peritoneal metastases, as well as to evaluate its correlation with clinico-pathological parameters. In total, 194 treatment naïve paired EOC and peritoneal metastasis were analyzed by immunohistochemistry for PD-L1 expression. Clinico-pathological information was available for all patients. Significant differences in PD-L1 expression were found between primary EOC and peritoneal metastasis (p < 0.0001). We found discordant tumor cell PD-L1 expression between primary tumors and corresponding peritoneal metastasis in 34% (66/194) of cases. Furthermore, PD-L1 expression in peritoneal metastasis samples was significantly associated with adverse prognostic factors, such as high proliferative index (Ki67) (p = 0.0039) and high histologic grade (p = 0.0330). In conclusion, the discordance of PD-L1 expression between primary EOC and corresponding peritoneal metastases suggests that its assessment as a potential biomarker for predicting response to anti-PD-L1 therapy may require analysis of metastatic lesions.

Efficacy Evaluation Of Albumin-Bound Paclitaxel Combined With Carboplatin As Neoadjuvant Chemotherapy For Primary Epithelial Ovarian Cancer

Background: This study aimed to compare the efficacy of albumin-bound paclitaxel combined with carboplatin (Nab-TC) with that of traditional solvent-based paclitaxel combined with carboplatin (TC) as a neoadjuvant chemotherapy regimen for primary epithelial ovarian cancer. Methods: Seventy-six patients with advanced primary epithelial ovarian cancer admitted for treatment at the Third Affiliated Hospital of Harbin Medical University from January 2015 to August 2020 were retrospectively selected. All patients underwent surgery after two courses of neoadjuvant chemotherapy with a combination of paclitaxel and carboplatin. Among the patients included for study, 34 were in the Nab-TC program and 42 in the TC program. Results: After two courses of chemotherapy, the ORR value was 52.38% in the TC group and 58.82% in the Nab-TC group (P=0.355). The CA125 value of the Nab-TC group decreased by 88.28% and that of the TC group by 86.99% (P=0.358). Overall operation time, intraoperative blood loss and postoperative hospital time of patients in the Nab-TC group were lower (P>0.05) and length of total hospital stay was significantly lower (P<0.05) relative to the TC group. Moreover, incidence of bone marrow suppression, abnormal liver function, arrhythmia and hyperglycemia in the Nab-TC group were lower (P>0.05) and total incidence of nausea and vomiting as well as grade III and IV stages were significantly lower (P<0. 05) than those in the TC group. However, the frequency of acral numbness in Nab-TC group was higher compared to the TC group (P<0.05). Conclusion: The efficacy of the Nab-TC regimen as neoadjuvant chemotherapy for advanced primary epithelial ovarian cancer was equivalent to that of the TC regimen, along with a lower incidence of adverse reactions, supporting its therapeutic value in the clinic.