Chlorine, chromium, proteins of oxidative stress and DNA repair pathways are related to prognosis in oral cancer.

The comparison of chemical and histopathological data obtained from the analysis of excised tumor fragments oral squamous cell carcinoma (OSCC) with the demographic and clinical evolution data is an effective strategy scarcely explored in OSCC studies. The aim was to analyze OSCC tissues for protein expression of enzymes related to oxidative stress and DNA repair and trace elements as candidates as markers of tumor aggressiveness and prognosis. Tumor fragments from 78 OSCC patients that had undergone ablative surgery were qualitatively analyzed by synchrotron micro-X-ray fluorescence for trace elements. Protein expression of SOD-1, Trx, Ref-1 and OGG1/2 was performed by immunohistochemistry. Sociodemographic, clinical, and histopathological data were obtained from 4-year follow-up records. Disease relapse was highest in patients with the presence of chlorine and chromium and lowest in those with tumors with high OGG1/2 expression. High expression of SOD-1, Trx, and Ref-1 was determinant of the larger tumor. Presence of trace elements can be markers of disease prognosis. High expression of enzymes related to oxidative stress or to DNA repair can be either harmful by stimulating tumor growth or beneficial by diminishing relapse rates. Interference on these players may bring novel strategies for the therapeutic management of OSCC patients.

Myokines in treatment-naïve patients with cancer-associated cachexia.

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N = 62), or not (weight stable cancer, WSC, N = 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p = 0.047), higher FABP3 plasma content (p = 0.0301) and higher tumor tissue expression of FABP3 (p = 0.0182), IL-15 (p = 0.007) and irisin (p = 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p = 0.0149, p = 0.0455 and p = 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p = 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may contribute to the systemic scenario), and put forward new perspectives on cachexia treatment targeting myokines and associated receptors and pathways.