ABSTRACT
PURPOSE: Nodal marginal zone lymphoma (NMZL) localized to a single lymphatic region (ie, stage I) is a relatively rare diagnosis. Current guidelines permit these patients to be either observed or treated with systemic therapy (ST), radiation therapy (RT), or both modalities. The prognostic effect of ST or RT compared with observation has not been established. The purpose of this study was to assess the prognostic effect of therapy in stage I NMZL. METHODS AND MATERIALS: The National Cancer Database was queried (2004-2018) for all patients with stage I NMZL. Patients were stratified based on treatment received. Propensity score matching (PSM) was performed overall and for each disease site to create 1:1 matched cohorts of patients who received RT and those who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable (UVA) and multivariable Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS. Subset analysis excluded patients deceased within 1 month of diagnosis to account for immortal time bias. RESULTS: A total of 3201 patients (median age 67) met inclusion criteria. A total of 1042 patients (33%) were head/neck/face, 208 (7%) intrathoracic, 613 (19%) intra-abdominal, 382 (12%) axilla/upper extremity, 292 (9%) inguinal/lower extremity, 86 (3%) pelvic, and 578 (18%) unspecified. A total of 1562 patients (49%) received no treatment, 721 (23%) received ST alone, 799 (25%) received RT alone, and 119 (4%) received both ST and RT. After PSM, ST was not prognostic on UVA while RT was prognostic on both UVA and multivariable analysis. After PSM, the 5-year OS was 84% for those who received RT and 79% for those who did not (P = .026). On subset analysis, these findings remained statistically significant for the head/neck/face cohort and the axilla/upper extremity cohort. After accounting for immortal time bias and performing PSM on this subset, the 5-year OS was 82% for those who received RT and 77% for those who did not (P = .047). CONCLUSIONS: In the overall cohort, RT improved OS compared with no RT, and ST was not a factor associated with OS. A radiation oncologist should be consulted for all patients with stage I NMZL for multidisciplinary decision making.
Subject(s)
Lymphoma , Humans , Aged , Prognosis , Kaplan-Meier EstimateABSTRACT
BACKGROUND: Increased expression of the progesterone receptor membrane component 1, a heme and progesterone binding protein, is frequently found in triple negative breast cancer tissue. The basis for the expression of PGRMC1 and its regulation on cellular signaling mechanisms remain largely unknown. Therefore, we aim to study microRNAs that target selective genes and mechanisms that are regulated by PGRMC1 in TNBCs. METHODS: To identify altered miRNAs, whole human miRNome profiling was performed following AG-205 treatment and PGRMC1 silencing. Network analysis identified miRNA target genes while KEGG, REACTOME and Gene ontology were used to explore altered signaling pathways, biological processes, and molecular functions. RESULTS: KEGG term pathway analysis revealed that upregulated miRNAs target specific genes that are involved in signaling pathways that play a major role in carcinogenesis. While multiple downregulated miRNAs are known oncogenes and have been previously demonstrated to be overexpressed in a variety of cancers. Overlapping miRNA target genes associated with KEGG term pathways were identified and overexpression/amplification of these genes was observed in invasive breast carcinoma tissue from TCGA. Further, the top two genes (CCND1 and YWHAZ) which are highly genetically altered are also associated with poorer overall survival. CONCLUSIONS: Thus, our data demonstrates that therapeutic targeting of PGRMC1 in aggressive breast cancers leads to the activation of miRNAs that target overexpressed genes and deactivation of miRNAs that have oncogenic potential.
