Abstract P6-07-22: Association of Hedgehog signaling pathway with luminal B sub-type of breast cancer affected patients of Pakistan
Authors: SK Riaz, R Rashid, STA Shah, F Wang, MFA Malik
Journal: Cancer Research (2017)

Abstract Introduction Hedgehog pathway dysregulation is observed in different types of cancers including breast. In the present study, expression profiles of hedgehog pathway molecules in breast cancer cohort of Pakistan and their probable association with molecular sub-types were explored. Methods The study was preceded with ethical approval and informed consent from respective institutions and participants. During 2013-2015, a total of 150 cancer biopsies along with adjacent normal tissues were prospectively collected immediately after surgery and processed for RNA isolation. Transcriptional profiles of salient members including SHH, DHH, IHH, PTCH-1, SMO and GLI-1 were quantified using qRT-PCR. Cohort was categorized into molecular sub-types following St. Gallen International Expert Consensus System. Association of expression levels of these aforementioned molecules with various clinico-pathological parameters was explored. Result Both SHH (p=0.01) and DHH (p&amp;lt;0.001) showed elevated expression among tumors in comparison to their controls. Similarly, PTCH-1 (p&amp;lt;0.001) and GLI-1 (p=0.002) were also significantly up regulated in the cohort. Interestingly, strong positive correlations were observed among the pathway molecules (r-value ranging from 0.45 to 0.81) which highlight their interdependence towards tumor progression. A significant correlation of SHH, DHH, PTCH-1 and GLI-1 was observed with advanced tumor sizes, stages, grades and nodal involvement (p&amp;lt;0.05). Association of IHH, SMO and GLI-1 over expression with cancer metastasis was also established in the cohort. SHH, PTCH-1 and GLI-1 were significantly linked with laterality, age and menopausal status. Expression of SHH (p=0.002) was more related to younger age group (mean age &amp;lt; 45 yrs) patients in comparison to elderly women. Moreover all hedgehog molecules were strongly related to hormonal receptors (ER and PR) (r-value ranging from 0.51 to 0.86) while over-expression of HER-2 was not associated with any pathway component. Briefly, 53% (79) of the cohort was categorized as Luminal-B, 18% (27) triple negative, 15% (23) Luminal-A and 14% (21) HER-2 for sub-typing of breast cancer patients in the cohort. Expression of SHH was significantly associated with the molecular sub-types (p=0.02) and age (p=0.005) using Pearson Chi-Square test. Elevated expression of SHH was observed in 60% of the patients in Luminal B sub-type. Conclusion Hedgehog pathway plays a crucial role in breast cancer progression and is found to be activated in Luminal B sub-type in this cohort. As Luminal B is a more aggressive type of breast cancer having poor prognosis and early-onset, association of SHH with Luminal-B and younger age patients signify it importance as a biomarker for early diagnosis of young patient's. Hence therapeutic interventions for hedgehog pathway can improve the prognosis of patients categorized as Luminal B subtype of breast carcinogenesis. Citation Format: Riaz SK, Rashid R, Shah STA, Wang F, Malik MFA. Association of Hedgehog signaling pathway with luminal B sub-type of breast cancer affected patients of Pakistan [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-22.