Project description:Using gene expression microarrays, we tested whether lung SCCs that have metastasised to loco-regional lymph nodes (N1/2m) are different to those that directly invade and involve local nodes (N1d). Using 22,323 element microarrays, a non-parametric test identified 126 genes/transcripts that discriminated between N0 (n=35) and N1/2m (n=16) tumours (Wilcoxon-Mann-Whitney U test, P<0.01). Hiearchical clustering of all 59 tumours (including 8 N1d tumours) demonstrated the N1d tumours clustered with the N0 tumours rather than the N1/2m tumours. Next, we built class prediction models from the 35 N0 tumours and 16 N1/2m tumours to predict the class of N1d tumours. All models consistently classified N1d tumours as similar to N0 tumours. This could explain some of the variable response of some N1 tumours to adjuvant chemotherapy, and suggest refinement of the TNM "N" stage nomenclature to adjust for this biological observation to ensure appropriate patients benefit from treatment. Keywords: non-small cell lung carcinoma, squamous cell, nodal metastasis, TNM staging, expression profiling Expression profiling using 22K element microarrays of 59 primary lung squamous cell carcinomas.
Project description:Using gene expression microarrays, we tested whether lung SCCs that have metastasised to loco-regional lymph nodes (N1/2m) are different to those that directly invade and involve local nodes (N1d). Using 22,323 element microarrays, a non-parametric test identified 126 genes/transcripts that discriminated between N0 (n=35) and N1/2m (n=16) tumours (Wilcoxon-Mann-Whitney U test, P<0.01). Hiearchical clustering of all 59 tumours (including 8 N1d tumours) demonstrated the N1d tumours clustered with the N0 tumours rather than the N1/2m tumours. Next, we built class prediction models from the 35 N0 tumours and 16 N1/2m tumours to predict the class of N1d tumours. All models consistently classified N1d tumours as similar to N0 tumours. This could explain some of the variable response of some N1 tumours to adjuvant chemotherapy, and suggest refinement of the TNM "N" stage nomenclature to adjust for this biological observation to ensure appropriate patients benefit from treatment. Keywords: non-small cell lung carcinoma, squamous cell, nodal metastasis, TNM staging, expression profiling
Project description:We performed an expression profiling study of 168 primary breast tumors, lymph node metastases, and autopsy samples of primary breast tumours and metastases to liver, chest wall, lymph node, lung, and spleen, as well as positive and negative RNA controls, with technical replicates, to assess quality control methodology and probe-level reproducibility of the Illumina DASL microarray assay. The experiment included both Illumina DASL HumanRef-v3 and DASL HT-12; this series includes only the 120 HumanRef-v3 samples . This series includes 120 samples in total: 19 autopsy tissues of the chest wall, liver, lymph nodes, lung, spleen, liver, and breast, 5 negative controls, 6 positive controls, and 90 lymph node metastases.
Project description:Cancer-associated fibroblasts (CAFs) play a pivotal role in the tumor microenvironment. We conducted an analysis using RNA sequencing to identify specific markers for CAFs compared to normal fibroblasts (NFs) in non-small cell carcinoma (NSCLC) under various condition. We analyzed 22 CAF samples and 11 NF samples. The 22 CAF samples consisted of 12 adenocarcinomas and 10 squamous cell carcinomas (SqCC), with 16 samples from the lungs and 6 samples from the lymph nodes. Notably, COL11A1, GREM1, CD36, and GAS6 showed higher expression in CAFs than in NFs, whereas TNC and CXCL2 were more highly expressed in NFs. CD36 levels were elevated in CAFs from lymph nodes (LN-CAFs) compared with those from lung specimens (Lung-CAFs) and NFs. COL11A1 levels in Lung-CAFs surpassed those in LN-CAFs and NFs. Both GREM1 and GAS6 showed strong expression in Lung-CAFs and LN-CAFs relative to NFs. CAFs exhibited features of the myofibroblast CAF subpopulation, whereas NFs displayed traits of the antigen-presenting CAF subtype. In NSCLC, GREM1 and GAS6 can be valuable diagnostic and therapeutic targets for CAFs from primary tumors and metastatic sites; they warrant further study.
Project description:We performed an expression profiling study of 168 primary breast tumors, lymph node metastases, and autopsy samples of primary breast tumours and metastases to liver, chest wall, lymph node, lung, and spleen, as well as positive and negative RNA controls, with technical replicates, to assess quality control methodology and probe-level reproducibility of the Illumina DASL microarray assay. The experiment included both Illumina DASL HumanRef-v3 and DASL HT-12; this series includes only the 48 HT12 samples . This series includes 48 samples in total: 9 positive controls, 4 negative controls, and 35 primary breast tumors and metastatic lymph nodes.
Project description:This research will evaluate the role of tissue proteome profile in regional metastatic disease. Considering that one of the main factors of survival in patients with papillary thyroid carcinoma is the presence of regional or distant metastatic disease, this research will focus on the difference in the proteome profiles between papillary thyroid carcinomas which had regional metastatic disease present at the time of surgery, and ones that did not have regional metastatic disease in neck lymph nodes at the time of surgery. In this study, 10 samples of papillary thyroid carcinomas without regional metastatic disease and 10 samples of well-differentiated papillary thyroid carcinomas with regional metastatic disease will be analyzed. The goal of this research is to try to identifiy certain differences in tissue proteomic profiles of papillary thyroid carcinoma depending on the presence of regional metastatic disease in neck lymph nodes.
Project description:Background. The unknown tissue of origin in head and neck cancer of unknown primary (hnCUP) leads to invasive diagnostic procedures and unspecific and potentially inefficient treatment options for patients. The most common histological subtype, squamous cell carcinoma, can stem from various tumor primary sites, including the oral cavity, oropharynx, larynx, head and neck skin, lungs, and esophagus. DNA methylation profiles are highly tissue-specific and have been successfully used to classify tissue origin. We therefore developed a support vector machine (SVM) classifier trained with publicly available DNA methylation profiles of commonly cervically metastasizing squamous cell carcinomas (n = 1,103) in order to identify the primary tissue of origin of our own cohort of squamous cell hnCUP patient’s samples (n = 28). Methylation analysis was performed with Infinium MethylationEPIC v1.0 BeadChip by Illumina. Results. The SVM algorithm achieved the highest overall accuracy of tested classifiers, with 87%. Squamous cell hnCUP samples on DNA methylation level resembled squamous cell carcinomas commonly metastasizing into cervical lymph nodes. The most frequently predicted cancer localization was the oral cavity in 11 cases (39%), followed by the oropharynx and larynx (both 7, 25%), skin (2, 7%), and esophagus (1, 4%). These frequencies concord with the expected distribution of lymph node metastases in epidemiological studies. Conclusions. On DNA methylation level, hnCUP is comparable to primary tumor tissue cancer types that commonly metastasize to cervical lymph nodes. Our SVM-based classifier can accurately predict these cancers’ tissues of origin and could significantly reduce the invasiveness of hnCUP diagnostics and enable a more precise therapy after clinical validation.