Search

Deleted in Liver Cancer-1 (DLC1) is a Rho-GTPase-activating protein known to be downregulated and function as a tumor suppressor in numerous solid and hematological cancers. Its expression status in melanoma is currently unknown however, prompting us to examine this. Using immunohistochemistry and tissue microarrays containing a large set of melanocytic lesions (n=539), we examined the expression profile of DLC1 in melanoma progression, as well as the association between DLC1 and patient survival. We detected both cytoplasmic and nuclear DLC1 expression, and found that whereas cytoplasmic DLC1 was significantly downregulated in metastatic melanoma compared with nevi and primary melanoma, nuclear DLC1 expression was significantly down in primary melanoma compared with nevi, and then further down in metastatic melanoma. Loss of cytoplasmic DLC1 was significantly associated with poorer overall and disease-specific 5-year survival rates of all melanoma (P<0.001 and P=0.001, respectively) and metastatic melanoma patients (P=0.020 and 0.008, respectively), and similar results were seen for nuclear DLC1 (P<0.001 for both overall and disease-specific survival for all melanoma patients, and P=0.004 for metastatic melanoma patients). Next, we examined the correlation between cytoplasmic and nuclear DLC1 and found that concomitant loss of both forms was associated with the worst outcome for metastatic melanoma patients (P=0.013 and P=0.008 for overall and disease-specific 5-year survival, respectively). Finally, multivariate Cox regression analysis determined that strong cytoplasmic and nuclear DLC1 expression was a favorable independent prognostic factor for all melanoma (HR, 0.61; 95% CI, 0.42–0.88; P=0.008) and metastatic melanoma patients (HR, 0.42; 95% CI, 0.23–0.77; P=0.005). Although more research still needs to be done on the topic, these preliminary results support the hypothesis that DLC1 is a tumor suppressor in melanoma.

Deleted in Liver Cancer-1 (DLC1) is a Rho-GTPase-activating protein known to be downregulated and function as a tumor suppressor in numerous solid and hematological cancers. Its expression status in melanoma is currently unknown however, prompting us to examine this. Using immunohistochemistry and tissue microarrays containing a large set of melanocytic lesions (n=539), we examined the expression profile of DLC1 in melanoma progression, as well as the association between DLC1 and patient survival. We detected both cytoplasmic and nuclear DLC1 expression, and found that whereas cytoplasmic DLC1 was significantly downregulated in metastatic melanoma compared with nevi and primary melanoma, nuclear DLC1 expression was significantly down in primary melanoma compared with nevi, and then further down in metastatic melanoma. Loss of cytoplasmic DLC1 was significantly associated with poorer overall and disease-specific 5-year survival rates of all melanoma (P<0.001 and P=0.001, respectively) and metastatic melanoma patients (P=0.020 and 0.008, respectively), and similar results were seen for nuclear DLC1 (P<0.001 for both overall and disease-specific survival for all melanoma patients, and P=0.004 for metastatic melanoma patients). Next, we examined the correlation between cytoplasmic and nuclear DLC1 and found that concomitant loss of both forms was associated with the worst outcome for metastatic melanoma patients (P=0.013 and P=0.008 for overall and disease-specific 5-year survival, respectively). Finally, multivariate Cox regression analysis determined that strong cytoplasmic and nuclear DLC1 expression was a favorable independent prognostic factor for all melanoma (HR, 0.61; 95% CI, 0.42–0.88; P=0.008) and metastatic melanoma patients (HR, 0.42; 95% CI, 0.23–0.77; P=0.005). Although more research still needs to be done on the topic, these preliminary results support the hypothesis that DLC1 is a tumor suppressor in melanoma.

Mammalian COP9 signalosome (CSN) exists as two variant complexes containing either CSN7A or CSN7B paralogs of unknown functional specialization. Constructing knockout cells, we found that CSN7Aand CSN7Bhave overlapping functions in the deneddylation of cullin-RING ubiquitin ligases. Nevertheless, CSNCSN7Bhas a unique function in DNA double-strand break (DSB) sensing, being selectively required for ataxia telangiectasia mutated (ATM)-dependent formation of NBS1S343pand γH2AX as well as DNA-damage-induced apoptosis triggered by mitomycin C and ionizing radiation. Live-cell microscopy revealed rapid recruitment of CSN7B but not CSN7A to DSBs. Resistance of CSN7Bknockout cells to DNA damage is explained by the failure to deneddylate an upstream DSB signaling component, causing a switch in DNA repair pathway choice with increased utilization of non-homologous end joining over homologous recombination. In mice, CSN7Bknockout tumors are resistant to DNA-damage-inducing chemotherapy, thus providing an explanation for the poor prognosis of tumors with low CSN7B expression.

We propose a method that utilizes degeneration noise to reduce inter-page-crosstalk by encoding certain phase distribution according to the noise distribution in the signal region. Due to the phase correlation of noise, modulated degeneration noise can eliminate each other and thus the signal-to-noise ratio (SNR) can be improved. To evaluate the SNR improvement, we introduced a new parameter called noise ratio factor (NRF), which is defined as the ratio of SNR with phase encoding to SNR without phase encoding. Then we use NRF distribution to guide us to encode phase in the signal region in the most effective way. Numerical simulation study shows that special designed phase modulation can reduce inter-page-crosstalk.