Secondary lymphedema is characterized by lymphatic fluid retention and subsequent tissue swelling in one or both limbs that can lead to decreased quality of life. It often arises after loss, obstruction, or blockage of lymphatic vessels due to multifactorial modalities, such as lymphatic insults after surgery, immune system dysfunction, deposition of fat that compresses the lymphatic capillaries, fibrosis, and inflammation. Although secondary lymphedema is often associated with breast cancer, the condition can occur in patients with any type of cancer that requires lymphadenectomy such as gynecological, genitourinary, or head and neck cancers. MicroRNAs demonstrate pivotal roles in regulating gene expression in biological processes such as lymphangiogenesis, angiogenesis, modulation of the immune system, and oxidative stress. MicroRNA profiling has led to the discovery of the molecular mechanisms involved in the pathophysiology of auto-immune, inflammation-related, and metabolic diseases. Although the role of microRNAs in regulating secondary lymphedema is yet to be elucidated, the crosstalk between microRNAs and molecular factors involved in the pathological features of lymphedema, such as skin fibrosis, inflammation, immune dysregulation, and aberrant lipid metabolism have been demonstrated in several studies. MicroRNAs have the potential to serve as biomarkers for diseases and elucidation of their roles in lymphedema can provide a better understanding or new insights of the mechanisms underlying this debilitating condition.
Breast cancer-related lymphedema (BCRL) is a form of secondary lymphedema that is characterized by abnormal swelling of one or both arms due to the accumulation of lymph fluid in the interstitial tissue spaces, resulting from obstruction of the lymphatic vessels due to surgery insults, radiotherapy, or chemotherapy. Due to the multifactorial nature of this condition, the pathogenesis of secondary lymphedema remains unclear and the search for molecular factors associated with the condition is ongoing. This study aimed to identify serum microRNAs and adipokines associated with BCRL. Blood was collected from 113 breast cancer survivors and processed to obtain serum for small RNA-sequencing (BCRL vs. non-BCRL, n = 7 per group). MicroRNAs that were differentially expressed (fold change >1.5, p < 0.05) between lymphedema cases and those without lymphedema were further quantified in a validation cohort through quantitative reverse transcription PCR (BCRL n = 16, non-BCRL, n = 83). Leptin and adiponectin levels were measured in a combined cohort (BCRL n = 23, non-BCRL n = 90) using enzyme-linked immunosorbent assays. Two of the most significantly upregulated microRNAs, miR-199a-3p and miR-151a-3p, were strongly correlated with the onset of lymphedema and diabetes mellitus in the BCRL group. Leptin levels were higher in the BCRL cohort compared to the non-BCRL cohort (p < 0.05). A metabolic syndrome biomarker, the adiponectin/leptin ratio, was found to be lower in the BCRL group than in the non-BCRL group (median: 0.28 vs. 0.41, p < 0.05). Extensive studies on the mechanisms of the identified microRNAs and association of leptin with arm lymphedema may provide new insights on the potential biomarkers for lymphedema that should be followed up in a prospective cohort study.
Crassignathadanaugirangensis sp. n. (Araneae: Symphytognathidae) was discovered during a tropical ecology field course held at the Danau Girang Field Centre in Sabah, Malaysia. A taxonomic description and accompanying ecological study were completed as course activities. To assess the ecology of this species, which belongs to the ground-web-building spider community, three habitat types were surveyed: riparian forest, recently inundated riverine forest, and oil palm plantation. Crassignathadanaugirangensis sp. n. is the most abundant ground-web-building spider species in riparian forest; it is rare or absent from the recently inundated forest and was not found in a nearby oil palm plantation. The availability of this taxonomic description may help facilitate the accumulation of data about this species and the role of inundated riverine forest in shaping invertebrate communities.