Thoracic Cancer最新文献

Objective: To search for a new biomarker that can predict the efficacy and prognosis of tumor immunotherapy.

Method: FOXK2 genes were analyzed using single-cell sequencing in pan-cancer bulk RNA-seq from the TCGA database. We used algorithms to predict their immune infiltration. Functional enrichment and ChIP-seq identified potential downstream gene, FBXO32. FBXO32's role in cancer immune response was explored through analysis.

Results: Significant up-regulation of FOXK2 was observed in prostate adenocarcinoma (PRAD), uterine corpus endometrial carcinoma (UCEC), bladder urothelial carcinoma (BLCA), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and stomach adenocarcinoma (STAD), while no such increase was found in lung cancer (lung adenocarcinoma [LUAD], lung squamous cell carcinoma [LUSC]) or thyroid carcinoma (THCA) tumor and adjacent tissues. FOXK2 expression correlated with patient prognosis, with lower expression associated with better immune response and survival and higher expression of its downstream gene FBXO32 linked to worse overall survival (OS) and immune infiltration. FOXK2 has the potential to be used as a prognostic indicator and target for treatment in individuals with cancer.

Conclusion: Our research provides insights into the significance of FOXK2 in cancer and indicates its potential as both a prognostic indicator and target for treatment. The ribosome-associated pathways involving FOXK2 and FBXO32 could be pivotal in the advancement of tumors, offering possible avenues for targeted and individualized immunotherapy approaches. Additional research is required to completely understand the mechanisms that are responsible for the participation of FOXK2 and its subsequent gene FBXO32 in cancer, as well as to explore the possible advantages of focusing on FOXK2 for cancer treatment.

Background: This study aimed to compare long-term clinical outcomes of percutaneous needle biopsy (PCNB) versus surgical biopsy in patients with peripheral, small-sized clinical stage 1 non-small cell lung cancer (NSCLC) with computed tomography (CT)-defined visceral pleural invasion (VPI).

Methods: We retrospectively analyzed patients who underwent surgery for NSCLC with CT-defined VPI between 2010 and 2017. We excluded patients with non-peripheral NSCLC, or cancers > 3 cm. Propensity score matching was carried out to adjust for confounding variables. The primary endpoint was ipsilateral pleural recurrence-free survival, while secondary endpoints included overall survival and recurrence-free survival.

Results: Of the 1671 patients with peripheral, small-sized clinical stage 1 NSCLC with CT-defined VPI, 805 underwent PCNB, and 866 had a surgical biopsy. Propensity score matching assigned 562 patients to each group. Before matching, the PCNB group demonstrated worse baseline characteristics, including older age, higher smoking history, and more adverse pathological findings. After matching, the 5-year recurrence-free survival for ipsilateral pleural recurrence (98.6% vs. 96.0%, p = 0.002) and overall survival (93.8% vs. 90.2%, p = 0.003) were significantly higher in the surgical biopsy group compared with the PCNB group. Multivariable analysis revealed that PCNB significantly increased the risks of all-cause mortality and various recurrences before and after matching.

Conclusions: Compared with surgery biopsy, PCNB was associated with higher risks of all-cause mortality and recurrences, including ipsilateral pleural recurrence. PCNB should be considered with caution in cases of peripheral stage 1 NSCLC where CT-defined VPI is suspected.

The main problem: Squamous cell carcinoma is the second most prevalent type of non-small cell lung cancer. Analyzing the molecular mechanisms underlying lung carcinoma requires useful tools, such as squamous lung cancer cell lines.

Methods: A novel new lung squamous cell carcinoma cell line, OMUL-1, was developed from the primary lung cancer of a 74-year-old man. We assessed the characteristics and behavior of OMUL-1 cells were examined, including their growth kinetics, tumorigenicity in mice, histological properties, gene expression profiles using reverse transcription polymerase chain reaction (RT-PCR), and RNA sequencing and invasion assays.

Results: OMUL-1-an adherent cell line-resulted in 100% tumor formation when subcutaneously injected into mice. Histological analysis of the subcutaneous tumor using hematoxylin and eosin staining revealed squamous cell carcinoma with characteristics similar to those of the primary tumor (p40 and p63 were positive, and TTF-1 was negative). An invasion assay demonstrated that OMUL-1 had a lower invasion ability compared to that of other developed cell lines. RT-PCR analysis and RNA sequencing indicated that OMUL-1 cells expressed FGFR1, FGFR2, FGFR3, FGFR4, EGFR, HER2, ErbB3, ErbB4, VEGFR3, IGF1R, c-MET, PDGFRa, and PDGFRb. Additionally, picropodophyllin (an IGF1R inhibitor) significantly inhibited the growth of OMUL-1 cells. Immunohistochemistry revealed that IGF1R and PD-L1 were expressed in both the primary and subcutaneous tumors.

Conclusions: We developed a novel new squamous cell lung carcinoma cell line, OMUL-1, that expresses IGF1R and PD-L1.

Background: Protein tyrosine kinase 7 (PTK7) has been found to be highly expressed in non-small cell lung cancer (NSCLC), but its specific molecular mechanism needs to be further explored.

Methods: PTK7 mRNA expression in NSCLC tumor tissues was examined by quantitative real-time PCR. The protein levels of PTK7, ubiquitin-specific peptidase 8 (USP8), PIK3CB, and PI3K/AKT were determined by western blot. Human monocytes (THP-1) were induced into macrophages and then co-cultured with the conditioned medium of NSCLC cells. Macrophage M2 polarization was assessed by detecting CD206⁺ cells using flow cytometry. The interaction between PTK7 and USP8 or PIK3CB was assessed by Co-IP assay. Animal study was performed to evaluate the effects of PTK7 knockdown and PIK3CB on NSCLC tumorigenesis in vivo.

Results: PTK7 expression was higher in NSCLC tumor tissues and cells. After silencing of PTK7, NSCLC cell proliferation, invasion, and macrophage M2 polarization were inhibited, while cell apoptosis was promoted. USP8 enhanced PTK7 protein expression by deubiquitination, and the repressing effects of USP8 knockdown on NSCLC cell growth, invasion, and macrophage M2 polarization were reversed by PTK7 overexpression. PTK7 interacted with PIK3CB, and PIK3CB overexpression could abolish the regulation of PTK7 silencing on NSCLC cell progression. USP8 positively regulated PIK3CB expression by PTK7, thus activating PI3K/AKT pathway. Downregulation of PTK7 reduced NSCLC tumorigenesis by decreasing PIK3CB expression.

Conclusion: USP8-deubiquitinated PTK7 facilitated NSCLC malignant behavior via activating the PIK3CB/PI3K/AKT pathway, providing new idea for NSCLC treatment.

Background: This study aimed to evaluate the impact of antibiotic exposure on efficacy and adverse reactions in non-small cell lung cancer (NSCLC) patients receiving chemoimmunotherapy, and to explore any specific associations on the basis of antibiotic class.

Methods: A retrospective study was conducted on NSCLC patients who received chemoimmunotherapy in two Shandong hospitals between January 2018 and October 2023. The association between antibiotic exposure and progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and incidence of immune related adverse reactions (irAE) of patients were evaluated.

Results: Of the 316 patients, 134 (42.41%) received antibiotics (ATB group), and 182 (57.59%) did not (N-ATB group). There was no significant difference in PFS (aHR = 1.009, 95% CI: 0.770-1.323; p = 0.946) or OS (aHR = 1.420, 95% CI: 0.986-2.047; p = 0.060) between ATB and N-ATB groups. The impact on efficacy was related to the type of antibiotic. β-Lactams (aHR = 1.737, 95% CI: 1.148-2.629; p = 0.009), in particular β-lactam/β-lactamase inhibitor combinations (BLBLIs) (aHR = 1.885, 95% CI: 1.207-2.944, p = 0.005) were associated with poorer OS. However, quinolones (aHR = 1.192, 95% CI: 0.861-1.650; p = 0.291) were not associated with OS. The incidence of irAEs was not significantly different between ATB and N-ATB groups (p = 0.073), but was higher with BLBLIs (p = 0.013).

Conclusions: In NSCLC patients receiving chemoimmunotherapy, no significant difference was observed in efficacy and incidence of irAEs between the ATB and the n-ATB groups. In antibiotic class analysis, β-lactams and specifically BLBLIs were observed to be associated with worse OS.

Hemolytic anemia is a rare and unique complication of alectinib, not observed with other anaplastic lymphoma kinase (ALK) inhibitors. Here, we present a case of an ALK fusion-positive non-small-cell lung cancer (NSCLC) patient who developed liver failure due to diffuse liver metastasis at initial diagnosis. Treatment was initiated with low-dose alectinib, but the patient developed severe hemolytic anemia. Switching to lorlatinib allowed for the continuation of ALK inhibitor therapy and successful tumor reduction. ALK inhibitors are crucial for ALK fusion-positive NSCLC patients. Managing severe side effects by switching medications is essential to maintain effective therapy. In this case, lorlatinib effectively controlled the tumor and improved the patient's liver function and performance status. This case highlights the importance of adapting treatment strategies to manage adverse effects while ensuring the continued use of ALK inhibitors for optimal patient outcomes.

Objective: To analyze the pattern of lymph node metastasis in esophageal cancer based on the theory of membrane anatomy.

Methods: A retrospective analysis was conducted on 143 patients who underwent esophageal surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences from March 2021 to March 2022. Lymph node metastasis was observed and categorized according to postoperative T staging. The characteristics and patterns of lymph node metastasis in different regions were observed, and the lymph node metastasis patterns in patients with clinical T3 esophageal cancer were analyzed using membrane anatomy theory.

Results: Among the 143 patients with esophageal squamous cell carcinoma, 21 were treated with surgery alone, while the rest received preoperative adjuvant therapy. A total of 5456 lymph nodes were cleared from the 143 patients, with 204 positive lymph nodes, resulting in a positive rate of 3.74%. In the thoracic lymph node dissection, the metastatic rates exceeded 5% for the following regions: 106recR (17.36%), 106recL (12.5%), 107 (10.42%), and 108 (5.56%) station. When analyzing the abdominal lymph node metastasis, the metastatic rates exceeded 5% for regions 7 (13.19%), 3a (7.64%), 2 (6.94%), and 1 (6.25%) station. Group analysis of patients with esophageal squamous cell carcinoma before postoperative pathological T3 stage revealed an increasing trend in tumor lymph node metastasis rate with later T staging. Lymph node metastasis in region 106recR can occur early, with a metastasis rate of 18.37% in T1 tumors. Analysis of lymph node metastasis characteristics in 103 patients clinically staged as T3 showed that 3966 lymph nodes were cleared, with 186 positive nodes, resulting in a positive rate of 4.69%. Lymph node metastasis rates were higher in regions 106recL, 106recR, 107, 108, 110, 1, 2, 3a, and 7, all exceeding 5%.

Conclusion: The theory of membrane anatomy can effectively explain the pattern of lymph node metastasis in esophageal cancer.

Objective: To conduct a comparative analysis of clinicopathological data between mucinous micropapillary breast carcinoma (MUMPC) and pure mucinous carcinoma (PMC) without a micropapillary structure to elucidate the distinctive clinicopathological characteristics of MUMPC and their impact on prognosis.

Methods: This retrospective analysis included 325 patients diagnosed with mammary mucinous carcinoma admitted to Tianjin Cancer Hospital between July 2014 and December 2019, including 197 patients with MUMPC and 128 patients with PMC without a micropapillary structure. Clinicopathological features were compared, and factors influencing the prognosis of MUMPC were analyzed. Survival analysis was conducted using the Kaplan-Meier method, and univariate and multivariate prognostic analyses for MUMPC were performed using the Cox proportional hazard regression model.

Results: The median follow-up period was 76 months. In the MUMPC and PMC groups, the disease-free survival (DFS) rates at 3, 5, and 7 years were 95.4%, 90.4%, 89.8%, and 100%, 98.4%, and 96.9%, respectively, with a statistically significant difference between the two groups (p = 0.009). Tumor, node, and metastasis (TNM) stage, lymph node metastasis, and endocrine treatment were significant factors influencing the prognosis of the MUMPC group (p < 0.001). Multivariate analysis revealed that lymph node metastasis and endocrine therapy were independent prognostic factors in patients with MUMPC (p < 0.001). Compared with PMC, the MUMPC group exhibited a higher prevalence of HER2 (11.2% vs. 3.1%, p = 0.009) and Ki-67 overexpression (79.7% vs. 60.2%, p < 0.001).

Conclusion: The lymph node stage is the most crucial clinicopathological feature of MUMPC. Endocrine treatment strategy is an independent risk factor affecting the prognosis of MUMPC.

Purpose: This study aimed to investigate the accuracy of three fixation methods in patients with left breast cancer receiving whole breast radiotherapy: conventional breast bracket (BB), breast bracket combined with deep inspiration breath holding (DIBH), and cervical-thoracic integrated bracket (CTIB) combined with DIBH.

Methods: From January 2023 to September 2023, 84 patients who underwent left breast cancer radiotherapy with supraclavicular radiation after conservative surgery were included in this study, of which 25 patients were fixed by conventional BB, 34 patients by BB & DIBH, and 25 patients by CTIB & DIBH. Image registration was conducted around the treatment area, using the sternoclavicular joint and acromioclavicular joint as landmarks. Systematic and random errors were calculated to assess the accuracy of these fixation methods.

Results: Compared to the conventional BB group, the CTIB & DIBH group demonstrated significant improvements in accuracy across multiple dimensions, including left-right, superior-posterior, and anterior-posterior directions, as well as rotational errors in the sagittal and coronal planes. The CTIB & DIBH group showed a significant reduction of setup error in the anterior-posterior direction compared to the BB & DIBH group. The displacement of the acromioclavicular joint varied, with the CTIB & DIBH method showing more favorable outcomes.

Conclusion: DIBH method exhibited lower setup errors and more effective fixation of the acromioclavicular joint, especially when combined with CTIB, making it a recommended fixation method in adjuvant radiotherapy following breast-conserving surgery.

Objectives: Podoplanin (PDPN) expression in cancer-associated fibroblasts (CAFs) (CAF-PDPN) is considered a poor prognostic factor in nonsmall cell lung cancer, but little is known about its clinical significance in high-grade neuroendocrine carcinoma of the lung (HGNEC). This study examines the association between CAF-PDPN and stromal programmed death-ligand 1 (PD-L1) expression and the prognostic implications of CAF-PDPN and PD-L1 expression status in surgically resected HGNEC patients.

Methods: Immunohistochemical analyses were performed on 121 resected HGNEC specimens using antibodies against PDPN and PD-L1. Correlations between CAF-PDPN, stromal PD-L1 expression, and clinicopathologic features and their implications for survival were analyzed statistically.

Results: There were substantially more large-cell neuroendocrine carcinomas in the stromal PD-L1-positive group and more vascular invasion in the tumoral PD-L1-positive group. PDPN expression in CAF was moderately correlated with stromal PD-L1 expression (ρ = 0.567, p < 0.001). In a survival analysis combining CAF-PDPN and stromal PD-L1 status, the 5-year RFS rates for Group A: CAF-PDPN (+)/stromal PD-L1 (+), Group B: CAF-PDPN (+)/stromal PD-L1 (-), Group C: CAF-PDPN (-)/stromal PD-L1 (+), and Group D: CAF-PDPN (-)/stromal PD-L1 (-) were 62.0%, 46.8%, 17.5%, and 20.2%, respectively, with corresponding 5-year OS rates of 76.6%, 69.2%, 27.0%, and 25.3%. The log-rank test showed statistically significant differences among the groups in RFS (p < 0.001) and OS (p < 0.001).

Conclusions: There is a correlation between CAF-PDPN and tumoral/stromal PD-L1 expression, and positive status for either CAF-PDPN or stromal PD-L1 expression could be an independent favorable prognostic factor in surgically resected HGNEC patients.