Despite the advances in diagnostic imaging and treatment modalities, the risk stratification and final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through data mining from published transcriptomic database, topoisomerase IIα (TOP2A) was first identified as a differentially upregulated gene in NPC tissues, which implicates cell division via selective cleavage, rearrangement, and re-ligation of DNA strands. Given the roles of TOP2A in prognostication and in the frontline therapeutic regimen of common carcinomas, such as breast cancer, we explored TOP2A immunoexpression status and its associations with clinicopathological variables and survival in a well-defined cohort of NPC patients. TOP2A immunohistochemistry was retrospectively performed and analyzed using H-score method for biopsy specimens from 124 NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score larger than the median value were construed as featuring TOP2A overexpression. The findings were correlated with the clinicopathological variables, disease-specific survival (DSS) and distant metastasis-free survival (DMFS). TOP2A overexpression was significantly associated with American Joint of Cancer Committee (AJCC) stages III-IV (p = 0.019) and univariately predictive of adverse outcomes for DSS (p = 0.0078) and DMFS (p = 0.0003). In the multivariate comparison, TOP2A overexpression remained prognostically independent to portend worse DSS (p = 0.047, hazard ratio = 1.732) and DMFS (p = 0.003, hazard ratio = 2.569), together with advanced AJCC stages III-IV. TOP2A expression is upregulated in a subset of NPCs and its increased immunoexpression significantly correlated with advanced stages and tumor aggressiveness, justifying the potentiality of TOP2A as a prognostic biomarker and a novel therapeutic target of NPC.

The risk stratification and final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Our principal goals were to identify and validate targetable metabolic drivers relevant to pathogenesis of NPC using a published transcriptome. One prominently downregulated gene regulating amino acid metabolism was found to be argininosuccinate synthetase (ASS1). Attributable to epigenetic DNA methylation, ASS1 deficiency may link to the therapeutic sensitivity to the arginine-depriving agents and promote tumor aggressiveness through its newly identified tumor suppressor function. ASS1 immunohistochemistry was therefore examined in a well-defined cohort of 124 NPC biopsy specimens and in the neck lymph node metastases of another ten independent cases. For the latter, bisulphite pyrosequencing was performed to evaluate the extent of ASS1 gene methylation. ASS1 protein deficiency was identified in 64 of 124 cases (51.6%), significantly related to T3-T4 status (p = 0.006), and univariately associated with inferior local recurrence-free survival (p = 0.0427), distant metastasis-free survival (DMFS; p = 0.0036), and disease-specific survival (DSS; p = 0.0069). Together with advanced AJCC stages III-IV, ASS1 protein deficiency was also independently predictive of worse outcomes for the DFMS (p = 0.010, hazard ratio = 2.241) and DSS (p = 0.020, hazard ratio = 1.900). ASS1 promoter hypermethylation was detected in eight of ten neck nodal metastatic lesions by bisulphite pyrosequencing and associated with ASS1 protein deficiency (p < 0.001). In summary, ASS1 protein deficiency was seen in approximately a half of NPCs and associated with advanced T classification, DNA methylation, and clinical aggressiveness, consistent with its tumor suppressor role. This aberration may render pegylated arginine deiminase as a promising strategy for ASS1-deficient NPCs.

Data mining on public domain identified that stathmin 1 (STMN1) transcript was significantly higher expressed in nasopharyngeal carcinoma (NPC). Also known as the oncoprotein 18, STMN1 performs an important function in regulating rapid microtubule remodeling of the cytoskeleton in response to the cellular conditions. Immunoexpression of STMN1 was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high STMN1 expressions (50 %) were correlated with advanced age (p = 0.027), higher T stage (p = 0.003), and overall clinical stage (p = 0.006) by the 7th American Joint Committee of Cancer Staging. In multivariate analyses, high STMN1 expression emerged as an independent prognosticator for worse disease-specific survival (p = 0.001), distal metastasis-free survival (p = 0.003), and local recurrence-free survival (p = 0.006). Exogenous expression of E2F transcription factor 1 (E2F1) or/and its dimeric partner, transcription factor Dp-1 (TFDP1), notably induced the STMN1 protein level in a NPC-derived cell line, TW01. Accordingly, high STMN1 protein level is commonly associated with adverse prognosticators and confers tumor aggressiveness in patients with NPC, and its upregulation might be attributed to E2F1 and/or TFDP1 transactivation.

Despite recent improvements in the diagnosis and treatment, the final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through data mining from published transcriptomic database with further bioinformatic validation, fibronectin (FN1) was identified as a differentially upregulated gene in NPC tissues, which implicates the transition from epithelial to mesenchymal phenotype (EMT) and promotes metastasis. Given the roles of fibronectin in risk stratification and in the frontline therapeutics of common carcinomas, such as renal cell cancer, we explored fibronectin immunoexpression status and its associations with clinicopathological variables and survival in a well-defined cohort of NPC patients. Fibronectin immunohistochemistry was retrospectively performed and analyzed using H-score for 124 biopsy specimens from NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score higher than the median value were regarded as fibronectin overexpression. The findings were correlated with clinicopathological variables, EBV latent membrane protein 1 (LMP1) expression, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Fibronectin overexpression was significantly associated with American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.019) and LMP1 expression (p = 0.004), and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS (all p < 0.0001). In the multivariate comparison, fibronectin overexpression still remained prognostically independent to portend worse DSS (p < 0.01, hazard ratio = 5.958), DMFS (p < 0.01, hazard ratio = 5.728), and LRFS (p < 0.01, hazard ratio = 5.411) together with a vanced AJCC stages III-IV. Fibronectin is upregulated in a subset of NPCs, and its increased immunoexpression significantly correlated with advanced features, justifying the potentiality of fibronectin as a theragnostic biomaker of NPC.

Neoadjuvant concurrent chemoradiotherapy has been widely used for rectal cancer to improve local tumor control. The varied response of individual tumors encouraged us to search for useful biomarkers to predict the therapeutic response. The study was aimed to evaluate the prognostic impact of lipid biosynthesis-associated biomarkers in rectal cancer patients treated with preoperative chemoradiotherapy. Through analysis of the previously published gene expression profiling database focusing on genes associated with lipid biosynthesis, we found that HSD17B2 and HMGCS2 were the top two significantly upregulated genes in the non-responders. We further evaluated their expression by immunohistochemistry in the pre-treatment tumor specimens from 172 patients with rectal cancer and statistically analyzed the associations between their expression and various clinicopathological factors, as well as survival. High expression of HMGCS2 or HSD17B2 was significantly associated with advanced pre- and post-treatment tumor or nodal status (P < 0.001) and lower tumor regression grade (P < 0.001). More importantly, high expression of either HMGCS2 or HSD17B2 was of prognostic significance, with HMGCS2 overexpression indicating poor prognosis for disease-free survival (P = 0.0003), local recurrence-free survival (P = 0.0115), and metastasis-free survival (P = 0.0119), while HSD17B2 overexpression was associated with poor prognosis for disease-free survival (P <0.0001), local recurrence-free survival (P = 0.0009), and metastasis-free survival (P < 0.0001). In multivariate analysis, only HSD17B2 overexpression remained as an independent prognosticator for shorter disease-free survival (P < 0.001) and metastasis-free survival (P = 0.008). In conclusion, high expression of either HSD17B2 or HMGCS2 predicted poor susceptibility of rectal cancer to preoperative chemoradiotherapy. Both acted as promising prognostic factors, particularly HSD17B2.