Translational cancer research最新文献

Background: Cancer survivors have an elevated risk of developing a second primary malignancy (SPM) after radiation therapy (RT). Data on the association between RT and SPM are limited. Our aim was thus to investigate the impact of RT on the risk of developing SPMs and to evaluate the specific characteristics and prognostic outcomes.

Methods: We enrolled a pancancer cohort using data from the Surveillance, Epidemiology, and End Results registries spanning from January 1973 to December 2015. Multivariable Cox and the Fine-Gray competing risk regression were employed to assess the hazard ratio (HR) and 95% confidence interval (CI) of SPMs in patients who received RT in comparison to those with no RT (NRT). Poisson regression was used to evaluate the RT-associated risks (RR) and the standardized incidence ratio (SIR) for SPMs.

Results: The analysis identified 24 types of risk-increased SPMs (RI-SPMs), including malignancies of the oropharynx, hypopharynx, larynx, esophagus, lung, breast, liver, pancreas, stomach, colon, rectum, ovary, corpus uteri, ureter, vagina, urinary bladder, penis, testis, and kidney, among others. The cumulative incidence of those with RI-SPMs was higher than that of the NRT patients (19.8% vs. 15.3%; P<0.001). The RR for RI-SPMs decreased with increasing age at FPM diagnosis (aged 20-49 years: RR 1.52; age 50-69 years: RR 1.31; age 70 years: RR 1.21), and the RR increased with longer latency period following FPM diagnosis (60-119 months: RR 1.28; 120-239 months: RR 1.24; 240-360 months: RR 1.46). The 10-year overall survival of those with RI-SPMs was significantly lower than that of the matched NRT patients (28.5% vs. 31.7%; P<0.001).

Conclusions: Patients with RI-SPMs warrant greater attention given their time-cumulative onset risk and poor prognosis. Long-term surveillance is necessary for cancer survivors treated with RT.

Background: Genetic alterations have important roles in cancer development and progression. SKA2 (spindle and kinetochore associated complex subunit 2) is a mitotic component that plays a critical role in maintaining the silence of the metaphase plate and spindle checkpoint. However, the exact role of SKA2 in hepatocellular carcinoma (HCC) remains unclear. The current study aimed to comprehensively identify the function of SKA2 in HCC.

Methods: We utilized various databases and bioinformatics tools, such as The Cancer Genome Atlas (TCGA), survminer package, Tumor Immune Estimation Resource (TIMER), cBioPortal website, clusterProfiler package, gene set enrichment analysis (GSEA), miRWalk, TargetScanHuman8.0, miRDB, DIANA and Cytoscape to identify the role of SKA2 in HCC.

Results: Our results showed that patients with HCC exhibited a high SKA2 expression. Further, the SKA2 high expression group had a worse overall survival (OS). And SKA2 was associated with tumor stage and the immune system. In addition, 188 co-expression genes of SKA2 participated in some processes including cell cycle, DNA replication and so on. The tumor had a lower hsa-miR-19b-1-5p and hsa-miR-378a-5p expression, and these two microRNAs (miRNAs) were also correlated with OS. SNHG14, SNHG15, and SPCA6P-AS were significantly negatively correlated with hsa-378a-5p, and these three long non-coding RNAs (lncRNAs) showed a positive correlation with SKA2 (P<0.05). SKA2 is a member of competing endogenous RNA (ceRNA). Moreover, it is related to SPACA6P-AS/hsa-miR-378a-5p/SKA2, SNHG14/hsa-miR-378a-5p/SKA2, and SNHG15/hsa-miR-378a-5p/SKA2, which play significant roles in tumor progression.

Conclusions: SKA2 is associated with OS, tumor stage, and immune infiltrating cells in HCC. Thus, we propose that SKA2 functions as a ceRNA and influences tumorigenesis. These findings lay the foundation for future research in the field of HCC.

Background: Anoikis, as a specific form of programmed cell death, involves in tumor metastasis. However, there is still lacking of anoikis-related long non-coding RNA (lncRNA) risk signature in the diagnosis and prognosis of lung adenocarcinoma (LUAD). This study constructed a prognostic risk model by comprehensively analyzing anoikis-related lncRNAs which could effectively diagnose and predict the outcomes of LUAD patients.

Methods: A list of anoikis-related genes (ARGs) was retrieved from literatures. Anoikis-related lncRNAs were selected using co-expression analysis from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate regression analyses were used to construct a prognostic model. The performance of the risk signature in predicting the prognosis and clinical significance were determined by Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, univariate and multivariate regression analyses. Moreover, the differences of tumor immune microenvironment between the high- and low-risk groups were explored. Finally, a novel nomogram was developed by combining the signature and clinicopathological factors, and the association between lncRNAs and differential N6-methyladenosine (m6A) genes was analyzed by Spearman's analysis.

Results: A total of 1,694 anoikis-related lncRNAs were identified from 479 cases of LUAD. According to the univariate and multivariate Cox analyses, we established a prognostic risk model consisting of seven lncRNAs (AC026355.2, AL606489.1, AL031667.3, LINC02802, LINC01116, AC018529.1, and AP000844.2). This prognostic risk model could efficiently classify low- and high-risk patients. The area under the curve (AUC) value was 0.717, which indicated more powerful predictive capability than commonly used clinicopathological factors. The high- and low-risk groups demonstrated different immune microenvironment. Moreover, the nomogram also demonstrated good performance in predicting the prognosis. Twelve differential m6A regulators were identified, and RBM15 was found to be correlated positively with the hub lncRNA AL606489.1.

Conclusions: Our study constructed a prognostic risk model based on anoikis-related lncRNAs, which could provide novel perspective on the prognosis of LUAD patients.

Background: Robot-assisted surgery is widely performed for renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombi. Although many chemotherapeutic options are available for the treatment of unresectable RCC, there are very few reports on robot-assisted radical nephrectomy (RARN) with inferior vena cava thrombectomy (IVCT) after presurgical treatment with immune checkpoint inhibitors and tyrosine kinase inhibitors. We believe that pre-surgical treatment can provide minimally invasive surgical benefits to high-risk patients during the perioperative period.

Case description: A 77-year-old male with right RCC that invaded the IVC (cT3bN0M0, Mayo classification level III) underwent pembrolizumab and axitinib combination therapy because he had high surgical risk due to angina pectoris. The level of the tumor thrombus decreased from level III to II, and RARN with IVCT was then performed. Surgery was performed without complications, and the patient was discharged on postoperative day seven. The pathological diagnosis was clear cell RCC (ypT3b, G2). Adjuvant chemotherapy using pembrolizumab monotherapy is still ongoing.

Conclusions: In this report, the inferior vena cave tumor thrombus level was down staged from level III to level II by treatment with pembrolizumab and axitinib. RARN with IVCT was safely performed without complication completely under robotic assistance.

Background: Inducible nitric oxide synthase (iNOS) is expressed in non-small cell lung cancer (NSCLC) tumor cells and contributes to tumorigenesis. Nitric oxide, an indicator of airway inflammation, is concurrently produced in the airway epithelium. However, the interrelationships and predictive importance of iNOS remain unclear. This study aimed to investigate whether iNOS could serve as a novel biomarker for NSCLC.

Methods: Immunohistochemical analysis of iNOS expression in the tumor cells of 101 consecutive patients with NSCLC undergoing lung resection was conducted. The fractional exhaled nitric oxide (FeNO) levels were evaluated pre- and postoperatively using a clinically applied respiratory function testing device. iNOS expression was assessed by immunochemical staining for expression within tumor cells.

Results: iNOS expression in the tumor cells was significantly associated with squamous cell carcinoma (P<0.01). No significant correlation between the FeNO levels and iNOS expression scores existed; however, the FeNO levels in positive cases of squamous cell carcinoma were significantly higher than those in negative cases (P<0.01). The FeNO levels did not decrease in the iNOS-negative cases after tumor resection in the squamous cell carcinoma group but were significantly lower in the positive cases (P=0.03).

Conclusions: iNOS expression in tumor cells showed a characteristic tendency toward squamous cell carcinoma, suggesting its potential for FeNO-mediated localization and diagnosing lung cancer.

[This corrects the article DOI: 10.21037/tcr.2020.03.70.].

Background: Colorectal adenocarcinoma (COAD) is a malignant tumor with high mortality and low 5-year survival rate. Voltage-dependent anion channel 3 (VDAC3) is the least understood isoform of voltage-dependent anion-selective channels in the mitochondrial outer membrane. In this thesis, we aimed to investigate the prognostic value of VDAC3 and provide new insights into colon adenocarcinoma.

Methods: We utilized The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, Human Protein Atlas online database, and the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) database to analyze VDAC3 expression in COAD and assess patient survival rates. Univariate and multivariate Cox regression analyses were employed to evaluate VDAC3's prognostic significance for COAD. Gene set variation analysis (GSVA) was utilized to explore COAD-related signaling pathways associated with VDAC3. Additionally, we predicted the relationship between VDAC3 expression and anticancer drug sensitivity using the CellMiner database.

Results: In the TCGA database, VDAC3 demonstrated elevated expression levels in COAD, which was further validated by findings from the GEO database. Survival analysis conducted using Kaplan-Meier (K-M) curves highlighted that the patients with decreased VDAC3 expression exhibited significantly shorter overall survival durations. VDAC3 expression demonstrated correlation with COAD pathological stage. VDAC3 gene mutation was linked to COAD outcomes. Cox regression analysis showed that VDAC3 was an independent predictor. In addition, GSVA analysis showed that VDAC3 was closely related to mitochondria-related biological processes and involved in the occurrence and development of mitochondria-related diseases. Finally, analysis of the CellMiner database predicted that VDAC3 expression was positively correlated with chelerythrine and cladribine, but negatively correlated with Ergenyl.

Conclusions: Our study suggests that VDAC3 may be a potential biomarker for early diagnosis, prognosis, and treatment of COAD.

Background: At present, it is known that there is a possibility of pleural cavity and needle tract implantation metastasis after lung cancer puncture biopsy, but clinicians have not paid attention to this phenomenon, and the probability of occurrence is unknown. In this study, we aimed to study the probability of implantation metastasis after peripheral lung cancer biopsy.

Methods: The intraoperative isolated completely collapsed fresh intact human lung lobes of 30 patients with peripheral lung cancer were taken, and the tumor body was punctured. The pleural pinholes and puncture needle tips were repeatedly rinsed with normal saline respectively. The flushing solution was prepared as inoculum, and then the inoculum was smeared for microscopic examination to find cancer cells. The inoculum was inoculated subcutaneously into nude mice, and then the probability of pleural cavity and needle tract implantation metastasis after lung biopsy was indirectly obtained by obtaining the nude mice tumorigenesis rate.

Results: The tumorigenesis rate of nude mice in the pleural pinholes group was 3.3%, and the tumorigenesis rate of nude mice in the puncture needle tip group was 3.3%.

Conclusions: Patients with lung nodules suspected of being early stage cancer and who are fit for surgical resection may benefit from forgoing lung biopsies to avoid pleural cavity or needle tract seeding with tumor cells.

[This retracts the article DOI: 10.21037/tcr-20-2450.].