Background: Breast cancer is the most commonly diagnosed cancer among women, and resistance to chemotherapy presents a significant challenge in its treatment. Stanniocalcin-2 (STC2), a glycoprotein involved in calcium homeostasis and cellular stress responses, is frequently overexpressed in various human cancers. Despite its critical role in cellular adaptation to stress, the potential of STC2 as a biomarker for predicting chemotherapy response has not been evaluated. This study aimed to assess the potential of STC2 as a predictive biomarker of response to chemotherapy in breast cancer. Methods: We utilized publicly available databases to characterize STC2 expression in breast cancer patients and its role in predicting relapse-free survival (RFS). Moreover, we evaluated the treatment responses of patients subjected to chemotherapy, correlating their outcomes with STC2 expression levels to determine its potential as a predictive biomarker. Finally, we evaluated the STC2 expression levels in breast cancer cell lines following exposure to doxorubicin (Dox), the primary anthracycline used in chemotherapy, and they were contrasted with the publicly available dataset. Results: The analysis showed that STC2 is significantly overexpressed in luminal A breast cancer, where it is linked to genetic amplifications. High STC2 expression was associated with improved RFS in ER-positive patients but correlated with worse outcomes in ER-negative cases. Furthermore, in grade II ER-positive patients, higher STC2 expression is linked to better chemotherapy response, while in grade II ER-negative patients, it was associated with poorer response. Finally, STC2 downregulation was observed in response to Dox treatment. Conclusions: These findings suggest that STC2 expression serves as a predictive biomarker for chemotherapy response in grade II breast cancer patients.

Paleoclimate records have long documented the existence of multicentury hydroclimate anomalies in the Altiplano of South America. However, the causes and mechanisms of these extended events are still unknown. Here, we present a climate modeling experiment that explores the oceanic drivers and atmospheric mechanisms conducive to long-term precipitation variability in the southern Altiplano (18–25° S; 70–65 W; >3500 masl). We performed a series of 100-year-long idealized simulations using the Weather Research and Forecasting (WRF) model, configured to repeat annually the oceanic and atmospheric forcing leading to the exceptionally humid austral summers of 1983/1984 and 2011/2012. The aim of these cyclical experiments was to evaluate if these specific conditions can sustain a century-long pluvial event in the Altiplano. Unlike the annual forcing, long-term negative precipitation trends are observed in the simulations, suggesting that the drivers of 1983/1984 and 2011/2012 wet summers are unable to generate a century-scale pluvial event. Our results show that an intensification of the anticyclonic circulation along with cold surface air anomalies in the southwestern Atlantic progressively reinforce the lower and upper troposphere features that prevent moisture transport towards the Altiplano. Prolonged drying is also observed under persistent La Niña conditions, which contradicts the well-known relationship between precipitation and ENSO at interannual timescales. Contrasting the hydroclimate responses between the Altiplano and the tropical Andes result from a sustained northward migration of the Atlantic trade winds, providing a useful analog for explaining the divergences in the Holocene records. This experiment suggests that the drivers of century-scale hydroclimate events in the Altiplano were more diverse than previously thought and shows how climate modeling can be used to test paleoclimate hypotheses, emphasizing the necessity of combining proxy data and numerical models to improve our understanding of past climates.

Proxy records have long documented the existence of multicentury hydroclimate anomalies in the Altiplano of South America. However, the causes and mechanisms of these events are still largely unknown. Here we present the results of an innovative climate modelling experiment that explores the oceanic drivers and atmospheric mechanisms conducive to long-term precipitation variability in the southern part of the Altiplano (18–25° S). For doing so, we performed 100-yr-long hydroclimate simulations using a regional climate model forced by climatological conditions that resulted in pluvial December-January-February (DJF) seasons during historical times. Our modelling simulations produce long-term negative DJF precipitation trends for the southern Altiplano, suggesting that the mechanisms leading to historical wet summers are unable to sustain century-scale pluvials such as the ones documented in paleoclimate records. Our simulations show that permanent La Niña conditions, as well as SSTs anomalies in the southern tropical Atlantic, progressively reinforce upper and lower-troposphere features that inhibit moisture transport towards the Altiplano. We further observed increases in March-April-May precipitation, suggesting the emergence of a long-term seasonal shift. Our simulations reproduce a sustained northward migration of the Atlantic trade winds, resulting in contrasting hydroclimate responses between the Altiplano and the tropical Andes. The atmospheric processes associated with these differences provide a useful analogue for explaining divergences in proxy records. Our study shows how regional climate modelling can be used to test paleoclimate hypothesis, emphasizing the necessity of combining proxy and modelling data to improve our understanding of long-term hydroclimate change.