Oesophageal squamous cell carcinoma (ESCC) is a malignant tumour of the digestive system that is associated with high morbidity and mortality rates worldwide. With the increased use of immunotherap...

Background. Lung squamous cell carcinoma (LUSC) is one of the most common types of lung carcinoma and has specific clinicopathologic characteristics. In this study, we screened novel molecular biomarkers relevant to the prognosis of LUSC to explore new diagnostic and treatment approaches for this disease. Methods. We downloaded GSE73402 from the Gene Expression Omnibus (GEO) database. GSE73402 contains 62 samples, which could be classified as four subtypes according to their pathology and stages. Via weighted gene coexpression network analysis (WGCNA), the main module was identified and was further analyzed using differentially expressed genes (DEGs) analysis. Then, by protein-protein interaction (PPI) network and Gene Expression Profiling Interactive Analysis (GEPIA), hub genes were screened for potential biomarkers of LUSC. Results. Via WGCNA, the yellow module containing 349 genes was identified, and it is strongly related to the subtype of CIS (carcinoma in situ). DEGs analysis detected 180 genes that expressed differentially between the subtype of CIS and subtype of early-stage carcinoma (Stage I and Stage II). A PPI network of DEGs was constructed, and the top 20 genes with the highest correlations were selected for GEPIA database to explore their effect on LUSC survival prognosis. Finally, ITGA5, TUBB3, SCNN1B, and SERPINE1 were screened as hub genes in LUSC. Conclusions. ITGA5, TUBB3, SCNN1B, and SERPINE1 may have great diagnostic and prognostic significance for LUSC and have great potential to be new treatment targets for LUSC.

Background: Surgical intervention remains the primary therapeutic modality for managing multiple pulmonary nodules. However, in cases with bilateral pulmonary nodules, one‐stage bilateral resection is discouraged due to tumor aggressiveness and surgical invasiveness. In light of this, we investigated an innovative approach, termed one‐stage bilateral pulmonary nodule resection via unilateral thoracic cavity access.Methods: From July 2022 to September 2024, a cohort of 12 patients with bilateral pulmonary nodules were enrolled in this study. This technique involves initial unilateral transcostal incision for segmental or lobectomy of a nodule on one side, followed by bilateral mediastinal pleura incision through the anterior mediastinum, facilitating subsequent wedge resection of the contralateral nodule. Clinical and pathological data, along with perioperative imaging findings and follow‐up information, were systematically collected and subjected to a comprehensive retrospective analysis.Results: A total of 25 nodules were resected from 12 patients. Regarding surgical approaches, nine patients underwent right thoracic incision, while three patients underwent left thoracic incision. Intraoperatively, seven patients received bilateral wedge resections, whereas five patients underwent segmentectomy on one side combined with wedge resection on the contralateral side. R0 resection of the contralateral nodules was successfully achieved during the procedures. The average distance between the surgical margin and the contralateral nodules was 12.5 mm, ranging from 5 mm to 25 mm. Of the 12 patients, one (Patient 6) was lost to follow‐up, while the remaining 11 patients underwent postoperative chest CT examinations. The median follow‐up duration for these 11 patients was 105 days (range: 36–857 days). No evidence of bilateral pleural effusion or tumor recurrence was detected on follow‐up chest CT scans.Conclusions: This study offers the potential to concurrently address bilateral pulmonary nodules, thereby sparing patients from the need for a subsequent hospitalization for surgical intervention.

Background: Esophageal squamous cell carcinoma (ESCC) is a major malignancy of the upper gastrointestinal tract. Owing to limited actionable therapeutic targets, long-term outcomes remain unsatisfactory. This study aimed to investigate the prognostic value of non-myelinating Schwann cells (nmSCs) infiltration in ESCC and to identify potential upstream regulators and underlying mechanisms. Methods: nmSCs infiltration was quantified in ESCC transcriptomic datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) using single-sample gene set enrichment analysis (ssGSEA). Genes associated with nmSC infiltration were identified by weighted gene co-expression network analysis (WGCNA) and correlation analyses. Potential upstream regulators and signaling pathways were explored by pan-cancer analyses in the Tumor Immune Estimation Resource (TIMER) database. nmSCs infiltration and candidate regulator expression were validated in an independent surgical cohort by immunohistochemistry (IHC). In addition, to investigate the regulatory relationship between teashirt zinc finger homeobox 3 (TSHZ3) and neuregulin 1 (NRG1) and their effects on Schwann cells (SCs) function, a co-culture system of ESCC cells and SCs was established. Functional validation was performed by knocking down TSHZ3 in ESCC cells, followed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and Cell Counting Kit-8 (CCK-8) assays. A postoperative prognostic model incorporating nmSC infiltration was subsequently developed. Results: Elevated nmSCs infiltration was significantly associated with poor survival in ESCC. IHC validation further confirmed nmSCs infiltration as an independent prognostic risk factor in patients undergoing surgical resection. Integrated analyses identified TSHZ3 as a potential upstream regulator of SCs infiltration, potentially acting through the NRG1 pathway in ESCC and multiple other tumor types. IHC demonstrated a significant positive correlation between TSHZ3 expression and nmSCs infiltration. Further in vitro functional experiments confirmed that knockdown of TSHZ3 in ESCC cells significantly reduced NRG1 expression levels and inhibited the proliferative capacity of SCs in the co-culture system, providing more direct evidence for the TSHZ3-NRG1 regulatory axis. Conclusions: nmSCs infiltration predicts adverse prognosis in ESCC, and TSHZ3 may promote nmSCs infiltration via the NRG1 signaling axis.

Esophageal squamous cell carcinoma (ESCC), a malignant tumor of the digestive tract, exhibits high incidence and mortality rates. The emergence of cancer immunotherapy necessitates urgent investigation into immune-related mechanisms in ESCC and other malignancies. Utilizing TCGA data from 93 ESCC patients and two Gene Expression Omnibus (GEO) datasets, we identified target immune cells via single-sample gene set enrichment analysis (ssGSEA) and established a prognostic prediction model. Weighted gene co-expression network analysis (WGCNA) screened relevant genes, while the TIMER database analyzed associated signaling pathways. Using ESCC tissue sections from our institutional cohort of 110 patients, the expression levels of relevant proteins were evaluated by immunohistochemistry (IHC), and correlation analyses were performed to further assess these findings. Th17 cell infiltration was associated with poor prognosis in ESCC patients (P < 0.05). The nomogram showed favorable predictive performance, with a C-index of 0.808 (95% CI: 0.715–0.900). In the institutional cohort, high RAR-related orphan receptor C (RORC) expression was associated with poorer survival (P = 0.002), and RORC IHC score was identified as a prognostic risk factor (HR = 1.32, 95% CI: 1.07–1.63; P = 0.009). Kruppel-like transcription factor 7 (KLF7) expression correlated with interleukin-6 receptor (IL6R), interleukin-1 receptor type 1 (IL1R1), signal transducer and activator of transcription 3 (STAT3), and RORC expression in ESCC and other malignancies. IHC analysis further demonstrated positive correlations among KLF7, STAT3, and RORC expression in ESCC tissues. Functional assays showed that KLF7 knockdown reduced KLF7 and STAT3 expression in ESCC cells and suppressed Th17 cell proliferation. These findings suggest that Th17/RORC-related immune features have prognostic value in ESCC and that KLF7 may be involved in STAT3-associated Th17-related immune regulation.