Investigating isoform switching in RHBDF2 and its role in neoplastic growth in breast cancer.

Background: Breast cancer is the second leading cause of cancer-related deaths globally, and its prevalence rates are increasing daily. In the past, studies predicting therapeutic drug targets for cancer therapy focused on the assumption that one gene is responsible for producing one protein. Therefore, there is always an immense need to find promising and novel anti-cancer drug targets. Furthermore, proteases have an integral role in cell proliferation and growth because the proteolysis mechanism is an irreversible process that aids in regulating cellular growth during tumorigenesis. Therefore, an inactive rhomboid protease known as iRhom2 encoded by the gene RHBDF2 can be considered an important target for cancer treatment. Speculatively, previous studies on gene expression analysis of RHBDF2 showed heterogenous behaviour during tumorigenesis. Consistent with this, several studies have reported the antagonistic role of iRhom2 in tumorigenesis, i.e., either they are involved in negative regulation of EGFR ligands via the ERAD pathway or positively regulate EGFR ligands via the EGFR signalling pathway. Additionally, different opinions suggest iRhom2 mediated cleavage of EGFR ligands takes place TACE dependently or TACE independently. However, reconciling these seemingly opposing roles is still unclear and might be attributed to more than one transcript isoform of iRhom2. Methods: To observe the differences at isoform resolution, the current strategy identified isoform switching in RHBDF2 via differential transcript usage using RNA-seq data during breast cancer initiation and progression. Furthermore, interacting partners were found via correlation and enriched to explain their antagonistic role. Results: Isoform switching was observed at DCIS, grade 2 and grade 3, from canonical to the cub isoform. Neither EGFR nor ERAD was found enriched. However, pathways leading to TACE-dependent EGFR signalling pathways were more observant, specifically MAPK signalling pathways, GPCR signalling pathways, and toll-like receptor pathways. Nevertheless, it was noteworthy that during CTCs, the cub isoform switches back to the canonical isoform, and the proteasomal degradation pathway and cytoplasmic ribosomal protein pathways were significantly enriched. Therefore, it could be inferred that cub isoform functions during cancer initiation in EGFR signalling. In contrast, during metastasis, where invasion is the primary task, the isoform switches back to the canonical isoform.

Role of Uterine Artery Doppler Ultrasound in Predicting Pre-Eclampsia in High-Risk Women.

Background and objective Pre-eclampsia (PE) is a major cause of maternal morbidity and mortality. The utility of Doppler ultrasonography (U/S) in predicting PE has not been extensively explored. This study aimed to determine the role of Doppler U/S in predicting PE among high-risk women. Methodology This was a retrospective observational study conducted at the Department of Obstetrics and Gynecology of Abbasi Shaheed Hospital in Karachi, over a period of one year, from January 2019 till December 2019. A total of 325 women were initially screened for risk factors for PE. Among them, 75 women were eventually found to have risk factors for PE and hence included in the study. Uterine artery Doppler U/S was performed to evaluate uterine artery's flow velocity waveforms. They were then used to calculate the presence of diastolic notch and resistance index (RI). At each antenatal visit, the risk factors for PE such as BP, proteinuria, and signs and symptoms were noted. Women were labeled to have PE if they developed hypertension (BP >140/90) after 20 weeks of gestation in combination with proteinuria. Results Twenty women (28%) had a normal Doppler flow of the uterine arteries. In 54 (72%) women, a unilateral/bilateral RI >0.58 was observed, and 29 women (38.7%) had a bilateral Rl >0.58. Notching of the uterine artery was also observed in 42 (26.7%, unilateral/bilateral) and in 22 (29.3%) bilaterally. Among the 75 women, BP of 140/90 mmHg along with proteinuria was observed in 56 (76.7%) cases, which were hence diagnosed as PE. Based on the cutoff of Rl and notching of the uterine artery, the overall sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of Doppler U/S in predicting PE were 71.4%, 26.3%, 23.8%, and 74.1%, respectively. As far as individual Doppler U/S indices were concerned, RI >0.58 (unilateral/bilateral) was found to be most sensitive (71%), while the presence of uterine artery notch (unilateral/bilateral) was most specific in predicting PE. Conclusion Abnormal Doppler U/S has good overall sensitivity in predicting PE. Among individual Doppler indices, notching of uterine arteries had a better specificity compared to high RI.

Association of Apgar Score With Meconium Staining of Amniotic Fluid in Labor.

Objective This study aimed to determine the association of Apgar score with meconium staining of amniotic fluid in labor. Methodology A retrospective observational study was carried out through the non-probability convenient sampling technique at the Department of Obstetrics and Gynecology for a duration of six months. Only those women were selected who had more than 24 weeks of gestation period. The women were excluded on the basis of risk factors for fetal distress and breech in late labor. Results A total of 216 pregnant women were selected from the labor room in this study. The mean age of the women was 26.57±4.28 years. The gestational age of the women was 36.09±4.11 weeks. Moreover, the mean parity of pregnant women was 1.68±2.53. It has been observed that the women who had meconium staining, the neonates of 144(77.4%) women showed the Apgar score of less than six at one minute. However, for the women without meconium staining, the neonates of only 15(50%) women showed the Apgar score of less than six at the one-minute interval with a significant association (p=0.02). With respect to age groups, a significant association of meconium staining with Apgar score was noted in the 21-30 years age group, whereas, no significant association was seen in other age groups. Similarly, a significant association of meconium staining and Apgar score was noted in primiparous women, whereas, no significant association was noted in multiparous women. No significant association of Apgar score and meconium staining was seen with respect to the mode of delivery. Conclusion The study has found a relation between the Apgar score and meconium staining of amniotic fluid and reported that the Apgar score of less than six at one minute was significantly associated with meconium staining of amniotic fluid.