Social isolation is associated with elevated tumor norepinephrine in ovarian carcinoma patients

Abstract

Noradrenergic pathways have been implicated in growth and progression of ovarian cancer. Intratumoral norepinephrine (NE) has been shown to increase with stress in an animal cancer model, but little is known regarding how tumor NE varies with disease stage and with biobehavioral factors in ovarian cancer patients. This study examined relationships between pre-surgical measures of social support, depressed mood, perceived stress, anxiety, tumor histology and tumor catecholamine (NE and epinephrine [E]) levels among 68 ovarian cancer patients. We also examined whether associations observed between biobehavioral measures and tumor catecholamines extended to other compartments. Higher NE levels were found in advanced stage (p=0.006) and higher grade (p=0.001) tumors. Adjusting for stage, grade, and peri-surgical beta blockers, patients with a perceived lack of social support had significantly higher tumor NE (β=-0.29, p=0.012). A similar trend was seen for social support and ascites NE (adjusting for stage, peri-surgical beta blockers and caffeine: β=-0.50, p=0.075), but not for plasma NE. Other biobehavioral factors were not related to tumor, ascites, or plasma NE (p values >0.21). Tumor E was undetectable in the majority of tumors and thus E was not further analyzed. In summary, these results suggest that tumor NE provides distinct information from circulating plasma concentrations. Tumor NE levels were elevated in relationship to tumor grade and stage. Low subjective social support was associated with elevated intratumoral NE. As beta-adrenergic signaling is related to key biological pathways involved in tumor growth, these findings may have implications for patient outcomes in ovarian cancer.

Figure 1

Tumor NE in early and advanced stage ovarian cancer patients (P = 0.006). Ovarian cancer stage is shown on the X-axis and levels of tumor NE are shown on the Y-axis.

Figure 2

Tumor NE (A) and ascites NE (B) as a function of perceived social support. Norepinephrine values are transformed to log₁₀. Adjusting for stage, grade, and peri-surgical beta blockers, patients with poor social support had significantly higher tumor NE (β = −0.29, p=0.012) A similar trend was seen for social support and ascites NE (adjusting for stage, peri-surgical beta blockers and caffeine: β= −0.50, p=0.075, n=19). Higher scores on the X axis represent greater social support.