TRPV6 is over-expressed and promotes the proliferation and invasion in many cancers. The association between the expression of TRPV6 and clinical outcome in esophageal squamous cell carcinoma (ESCC) has not been studied yet. We aim to elucidate the role of TRPV6 in predicting prognosis of patients with ESCC. In the retrospective study, mRNA level of TRPV6 was examined in patients (N = 174) from Sun Yat-sen University Cancer Center (mRNA cohort) and protein level of TRPV6 was examined in patients (N = 218) from Linzhou Cancer Hospital (protein cohort). Statistical analysis was performed to test the clinical and prognostic significance of TRPV6. TRPV6 was down-regulated in ESCC tissues and cell lines. Patients with downregulation of TRPV6 trended to have a higher rate of advanced pT stage in both mRNA cohort (P = 0.089) and protein cohort (P = 0.073), though not statistically significant. No significant association was observed between TRPV6 expression and disease-specific survival (DSS) in both two cohorts. However, stratified survival analysis based on the gender showed that in mRNA cohort, downregulation of TRPV6 was associated with an unfavorable 3-year DSS in patients with male (47.3 % vs 63.6 %, P = 0.027) and with favorable 3-year DSS in patients with female (66.7 % vs 43.0 %, P = 0.031). The result was confirmed in protein cohort. Male patients with downregulation of TRPV6 had a poor 3-year DSS (20.0 % vs 57.1 %,P < 0.001) while female counterparts showed an enhanced 3-year DSS (56.1 % vs 28.6 %, P = 0.005). TRPV6 is down-regulated in ESCC. As a predictive biomarker, TRPV6 plays a Janus-like role in predicting survival of male and female ESCC patients.

Lung adenocarcinoma (LUAD) is the most prevalent and aggressive subtype of lung cancer, exhibiting a dismal prognosis with a five-year survival rate below 5%. DEAD-box RNA helicase 18 (DDX18, gene symbol DDX18), a crucial regulator of RNA metabolism, has been implicated in various cellular processes, including cell cycle control and tumorigenesis. However, its role in LUAD pathogenesis remains elusive. This study demonstrates the significant upregulation of DDX18 in LUAD tissues and its association with poor patient survival (from public databases). Functional in vivo and in vitro assays revealed that DDX18 knockdown potently suppresses LUAD progression. RNA sequencing and chromatin immunoprecipitation experiments identified cyclin-dependent kinase 4 (CDK4), a cell cycle regulator, as a direct transcriptional target of DDX18. Notably, DDX18 depletion induced G1 cell cycle arrest, while its overexpression promoted cell cycle progression even in normal lung cells. Interestingly, while the oncogenic protein c-Myc bound to the DDX18 promoter, it did not influence its expression. Collectively, these findings establish DDX18 as a potential oncogene in LUAD, functioning through the CDK4-mediated cell cycle pathway. DDX18 may represent a promising therapeutic target for LUAD intervention.

Background: Hepatitis B Virus (HBV) infection has been proven to be associated with the survival of many cancers. However, the prevalence and prognostic value of HBV infection in esophageal cancer has not been investigated yet. Methods: A total of 2,004 consecutive esophageal cancer patients who underwent esophagectomy between 2000 and 2008 were recruited in our study. ELISA was used to test serum HBV markers. Patients were divided into HBsAg-positive group (HBV infection) and HBsAg-negative group. The impact of HBV infection on disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan–Meier method and Cox proportional hazard models. Results: HBV infection was found in 12.6% (253/2,004) of patients. HBsAg-positive patients had significantly higher percentage of early pathologic T stage, lower frequency of liver metastasis, and extrahepatic metastasis than HBsAg-negative. HBsAg-positive patients had a favorable DFS [HR = 0.79; 95% confidence interval (CI): 0.66–0.94, P = 0.007) and OS (HR = 0.80; 95% CI: 0.65–0.95, P = 0.020] respectively, when compared with HBsAg-negative patients. Subgroup analysis showed that the association with HBV infection and better DFS and OS was observed in patients with esophageal squamous cell carcinoma and advanced pathologic stage (III–IV). Conclusion: HBV infection was an independent favorable prognostic factor for survival in operable esophageal cancer. Impact: Our large cohort study provided more definite and quantitative evidence that HBV infection is an independent favorable prognostic biomarker in patients with esophageal cancer, especially in patients with esophageal squamous cell carcinoma and advanced pathologic stage (III–IV).

Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m⁵C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6’s function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.

Background: The survival benefits of recurrent laryngeal nerve lymph node dissection (RLNLD) in esophageal squamous cell carcinoma (ESCC) are still under debate, and the prognostic value of unilateral RLNLD has been rarely studied. Therefore, the aim of the present study was to investigate the clinical significance and outcomes of RLNLD in ESCC in a large‐scale cohort study, to shed light on the outcomes of unilateral RLNLD, and to identify the factors that affect the prognostic outcome of RLNLD.Methods: We retrospectively reviewed 1153 patients with thoracic ESCC who underwent right thoracotomy with lymphadenectomy. The impact of RLNLD on disease‐free survival (DFS) and overall survival (OS) was estimated using the Kaplan–Meier method and Cox proportional hazard models. Inverse probability of treatment weighting (IPTW) was performed to adjust for differences in baseline variables in pairwise comparisons. Subgroup analysis of survival and postoperative complications was conducted for selective RLNLD.Results: RLN lymph node (LN) metastasis was independently associated with tumor location and most other LN station metastases. RLNLD was an independent prognostic factor for DFS and OS. Both patients who underwent unilateral and bilateral RLNLD had significantly better DFS and OS than the non‐RLNLD patients. Furthermore, pairwise comparisons with IPTW confirmed these results, and we found that patients who underwent bilateral RLNLD had better survival than those who underwent unilateral RLNLD. However, subgroup analysis showed that there was no survival benefit and higher morbidity after bilateral RLNLD for patients with cancer in the lower thoracic esophagus, and elderly and female patients.Conclusion: RLN LN metastasis is very frequent in ESCC, and both unilateral and bilateral RLNLD have considerable survival benefits. Selective RLNLD with better survival and lower morbidity was recommend for some defined subgroups.

Background: Accurate assessment of pathologic complete response (pCR) after neoadjuvant immunochemotherapy (NICT) is crucial to implement active surveillance or tailor therapeutic strategies for esophageal squamous cell carcinoma (ESCC), while reliable non-invasive methods for pCR prediction are lacking. We aimed to evaluate the potential of integrating circulating tumor DNA (ctDNA) and PET/CT for predicting pCR to NICT for ESCC. Methods: A total of 123 eligible patients were enrolled, including 68 patients from our prospective clinical trial (ChiCTR2000028900) and a real-world study (NCT04822103) that formed the discovery cohort, as well as 55 patients from another clinical trial (ChiCTR2100051763) comprising the validation cohort. Blood samples for ctDNA sequencing and PET/CT metrics were collected before and after NICT. Results: The ctDNA status and PET/CT parameters at the post-NICT stage rather than the pre-NICT stage significantly differentiated pCR from non-pCR patients. ctDNA and PET/CT synergistically enhanced the prediction of pCR from perspectives of sensitivity and specificity, respectively. The model integrating ctDNA concentration and mean standardized uptake value (SUVmean) demonstrated area under curves (AUCs) of 0.860 in the discovery cohort and 0.798 in the validation cohort for pCR prediction and stratified patients into high- and low-risk groups with differential survival prospects. The key gene modules converged on TP53 as the core mutation for pCR prediction, among which those located in the exon regions contributed the most to its predictive capacity. The model constructed based on TP53 mutation and SUVmean differentiated pCR from non-pCR with comparable performance to the model based on PET/CT and the overall ctDNA concentration. Conclusion: The combination of post-treatment TP53-centric ctDNA and PET/CT synergistically enhances the prediction of pCR following NICT in ESCC patients, indicating the potential to inform clinical decision-making for these patients.