Kyung Jin Eoh

The long noncoding RNA HOXA11 antisense induces tumor progression and stemness maintenance in cervical cancer

Recent research has focused on the impact of long noncoding RNA (lncRNA) in cervical carcinogenesis. However, whether HOXA11 antisense (HOXA11-AS) is involved in cervical cancer remains to be elucidated. In the present study, we examined HOXA11-AS expression levels in cervical cancer patients and determined the relationships between HOXA11-AS expression and clinicopathological factors. We also investigated the bio-functional consequences of HOXA11-AS overexpression both in vitro and in vivo. HOXA11-AS expression was significantly greater in tissues from patients with cervical cancer than in control patients (P<0.001). Multivariate analysis showed that high HOXA11-AS was an independent prognosticator of overall survival (Hazard ratio=2.450, P=0.032). HOXA11-AS overexpression enhanced cell proliferation, migration, and tumor invasion in vitro, whereas HOXA11-AS knockdown inhibited these biologic aggressive features. These adverse changes were accompanied by characteristics of epithelial-mesenchymal transition (EMT). In vivo xenograft experiments using the siHOXA11-AS-transfected HeLa cells revealed that HOXA11-AS strongly induced tumor growth. Furthermore, we found that HOXA11-AS knockdown decreased cancer stemness and triggered the EMT program. In conclusion, HOXA11-AS overexpression correlated with poor survival in patients with cervical cancer. Thus, HOXA11-AS may be a pivotal target for exploring novel cervical cancer therapeutics.

Role of surgical therapy in the management of gestational trophoblastic neoplasia

Objective To evaluate the role of adjuvant surgical procedures in the management of gestational trophoblastic neoplasia (GTN). Methods In a retrospective review of medical records at the Severance Hospital, we identified 174 patients diagnosed with GTN between 1986 and 2006. Of the 174 patients, 129 (74%) were assigned to the nonmetastatic group, and 45 (26%) to the metastatic group; of the metastatic group patients, 6 were in the low-risk group and 39 were in the high-risk group. Thirty-two patients underwent 35 surgical procedures as part of the GTN treatment. The procedures included hysterectomy, lung resection, craniotomy, uterine wedge resection, uterine suturing for bleeding, salpingo-oophorectomy, pretherapy dilatation and curettage, adrenalectomy, nephrectomy, and uterine artery embolization. Results Of the 32 patients who underwent surgical procedures, 28 (87%) survived. Eleven patients underwent surgery for chemoresistant disease after receiving one or more chemotherapy regimens. Twelve patients underwent procedures to control tumor hemorrhage. Nine (81%) of 11 patients with chemoresistant disease survived, and 8 patients who underwent salvage surgery for chemoresistant disease received further chemotherapy. Of 21 patients who underwent hysterectomy, 19 (90%) achieved remission. All of three patients who had resistant foci of choriocarcinoma in the lung achieved remission through pulmonary resection. Conclusion Adjuvant surgical procedures, especially hysterectomy and pulmonary resection for chemoresistant disease, as well as procedures to control hemorrhage, are pivotal in the management of GTN.

Malnutrition Identified by the Nutritional Risk Index and Poor Prognosis in Advanced Epithelial Ovarian Carcinoma

ABSTRACT Ovarian cancer is a chronic disease with a risk of malnutrition. Nutritional Risk Index (NRI) has been reported as a simple and accurate tool to assess the nutritional status. We sought to explore the prevalence of malnutrition and its association with survival in ovarian cancer. A retrospective study was conducted in 213 advanced ovarian cancer patients. NRI was calculated before and at the end of treatment using patients’ body weight and serum albumin level. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method, and associations were assessed using a Cox proportional hazards analysis adjusted for known prognostic variables. Moderate to severely malnourished patients had lower 5-yr OS (45.3%) compared to normal to mild group (64.0%), respectively (P = 0.024). Adjusted for covariates, the relative risk of death was 5.8 times higher in moderate/severely malnourished group identified at the last course of chemotherapy (HR = 5.896, 95% CI = 2.723-12.764, P < 0.001). Similarly, this cohort had shorter PFS compared with normal to mild risk group (median 15 vs. 28 months, P = 0.011). Malnutrition is prevalent among ovarian cancer patients and is found to be a significant predictor for mortality.

Long non-coding RNA, steroid receptor RNA activator (SRA), induces tumor proliferation and invasion through the NOTCH pathway in cervical cancer cell lines

Contemporary research has focused on the function of long non-coding RNAs (lncRNAs) in carcinogenesis. However, the involvement of the lncRNA, steroid receptor RNA activator (SRA), in cervical carcinogenesis remains to be elucidated. In the present study, we investigated the bio-functional consequences of lncRNA SRA knockdown in vitro. To verify the role of lncRNA SRA in cell proliferation, migration, and invasion, lncRNA RNA interference was utilized to knock down lncRNA SRA expression in cervical cancer cell lines, resulting in our discovery that lncRNA SRA knockdown inhibited cell proliferation, cell migration and tumor invasion in the cervical cancer cell lines. Additionally, in vitro experiments using the lncRNA SRA-knockdown cervical cancer cell lines revealed that lncRNA SRA is a strong inducer and modulator of the expression of genes related to epithelial-mesenchymal transition and the NOTCH signaling pathway. In conclusion, our findings demonstrated that lncRNA SRA is highly correlated with cancer progression and cervical cancer cell proliferation and migration. Furthermore, these results indicate that lncRNA SRA may be a potential therapeutic target and prognostic marker for cervical malignancy.

Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients

Purpose The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type). Materials and Methods We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status. Results Thirty-seven (37/116, 31.9%) BRCA1/2mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively). Conclusion Patientswith BRCA1/2 mutation had longer OS than thosewith BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.

Role of systematic lymphadenectomy as part of primary debulking surgery for optimally cytoreduced advanced ovarian cancer: Reappraisal in the era of radical surgery

The prognostic significance of pelvic and para-aortic lymphadenectomy during primary debulking surgery for advanced-stage ovarian cancer remains unclear. This study aimed to evaluate the survival impact of lymph node dissection (LND) in patients treated with optimal cytoreduction for advanced ovarian cancer. Data from 158 consecutive patients with stage IIIC–IV disease who underwent optimal cytoreduction (<1 cm) were obtained via retrospective chart review. Patients were classified into two groups: (1) lymph node sampling (LNS), node count <20; and (2) LND, node count ≥20. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Among the included patients, 96 and 62 patients underwent LND and LNS as primary debulking surgery, respectively. There were no differences in the extent of debulking surgical procedures, including extensive upper abdominal surgery, between the groups. Patients who underwent LND had a marginally significantly improved PFS (P = 0.059) and significantly improved OS (P < 0.001) compared with those who underwent LNS. In a subgroup with negative lymphadenopathy on preoperative computed tomography scans, revealed LND correlated with a better PFS and OS (P = 0.042, 0.001, respectively). Follow-ups of subsequent recurrences observed a significantly lower nodal recurrence rate among patients who underwent LND. A multivariate analysis identified LND as an independent prognostic factor for PFS (hazard ratio [HR], 0.629; 95% confidence interval [CI], 0.400–0.989) and OS (HR, 0.250; 95% CI, 0.137–0.456). In conclusion, systematic LND might have therapeutic value and improve prognosis for patients with optimally cytoreduced advanced ovarian cancer.

Long-Term Survival Analysis of Intraperitoneal versus Intravenous Chemotherapy for Primary Ovarian Cancer and Comparison between Carboplatin- and Cisplatin-based Intraperitoneal Chemotherapy

In epithelial ovarian cancer (EOC), intraperitoneal (IP) administration of chemotherapy is an effective first-line treatment and may improve outcomes, compared with intravenous (IV) chemotherapy. We used Kaplan-Meier survival analysis to compare long-term survival between propensity score-matched patients with advanced EOC receiving IP (n = 34) vs. IV (n = 68) chemotherapy. Additionally, clinical features associated with carboplatin-based (n = 21) and cisplatin-based (n = 16) IP chemotherapy were analyzed and compared with those associated with IV chemotherapy. The IP and IV chemotherapy groups had a median follow-up duration of 67 (range, 3–131) and 62 (range, 0–126) months, respectively, with no significant difference in progression-free survival (PFS) (P = 0.735) and overall survival (OS) (P = 0.776). A significantly higher proportion of patients in the IV (91.2%) than in the IP (67.6%) chemotherapy group (P = 0.004) received ≥ 6 cycles. However, the frequency of toxic events (anemia, granulocytopenia, nausea/vomiting, abdominal pain, hepatotoxicity, neuromuscular effects) was significantly higher in the IP than in the IV group. Within the IP group, no significant differences were observed in PFS (P = 0.533) and OS (P = 0.210) between the cisplatin-based and carboplatin-based chemotherapy subgroups. The 10-year OS was 28.6% and 49.2% in carboplatin-based and cisplatin-based IP chemotherapy groups, respectively. Toxic events (granulocytopenia, leukopenia, nausea/vomiting, abdominal pain, hepatotoxicity, neuromuscular effects) were significantly more common in the cisplatin-based subgroup. In patients with EOC, cisplatin-based IP chemotherapy may be an acceptable alternative to IV chemotherapy regarding long-term survival, but toxicity must be addressed.

Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2

Purpose Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS. Materials and Methods Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing. Results Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance. Conclusion Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

In-bag power morcellation technique in single-port laparoscopic myomectomy

Objective This study introduces and evaluates the feasibility, safety, and surgical outcomes of the in-bag power morcellation technique during single-port assisted (SPA) laparoscopic myomectomy in comparison with manual scalpel morcellation. Methods This is a retrospective review of a total of 58 patients who underwent SPA laparoscopic myomectomy employing in-bag power morcellation (n=27) or manual scalpel morcellation (n=31), performed between December 2014 and December 2016. Surgical outcomes, including total operation time, estimated blood loss, postoperative hemoglobin changes, postoperative hospital stay, postoperative pain (visual analog scale), perioperative and postoperative complications were evaluated. Results The demographics and patient characteristics were similar between both groups. The median patient age was 34 years and median body mass index was 20.84 kg/m2. The median specimen weight was 110 g. The median operating time was 138 minutes. The median estimated blood loss was 50 mL and the median postoperative hemoglobin change was 2.2 g/dL. The median postoperative hospital stay was 2 days and the median postoperative pain scores were 5 after 6 hours, 3 after 24 hours, and 2 after 48 hours. Occult malignancy was not identified in any patients. There were no intraoperative complications such as LapBag ruptures or gross spillage. Conclusion In-bag power morcellation for SPA laparoscopic myomectomy is feasible and safe, minimizing the risks of open power morcellation. There were also no statistically significant differences in surgical outcomes.

Upregulation of homeobox gene is correlated with poor survival outcomes in cervical cancer

HOX family members encode transcription factors crucial for embryogenesis and may be associated with carcinogenesis. Here, we evaluated the expression of 39 HOX genes in cervical cancer by using clinicopathological information and gene expression data of 308 patients from The Cancer Genome Atlas (TCGA) database. Correlations between mRNA expression of HOX family members and clinicopathological variables were explored. Seventy-three (23.7%) patients died during the follow-up period (median, 22.0 months). Overall mortality was significantly associated with advanced FIGO stage, lymph node metastasis, lymphovascular invasion, and increased HOXA1, HOXA5, HOXA6, and HOXC11 mRNA expression. Kaplan–Meier survival analysis revealed that overall survival was significantly shorter in patients with high HOXA rather than low HOXA expression (HOXA1, P = 0.012; HOXA5, P = 0.008; and HOXA6, P = 0.006). Upregulated HOXA1, HOXA5, and HOXA6 expression are significantly correlated with unfavorable overall survival and increased mortality in cervical cancer patients. Therefore, HOXA expression is a potential cervical cancer prognostic indicator.