Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response.

The spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell and spatial transcriptomic analysis on HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize malignant cells in tumor core (TC) and leading edge (LE) transcriptional architectures. We show that the TC and LE are characterized by unique transcriptional profiles, neighboring cellular compositions, and ligand-receptor interactions. We demonstrate that the gene expression profile associated with the LE is conserved across different cancers while the TC is tissue specific, highlighting common mechanisms underlying tumor progression and invasion. Additionally, we find our LE gene signature is associated with worse clinical outcomes while TC gene signature is associated with improved prognosis across multiple cancer types. Finally, using an in silico modeling approach, we describe spatially-regulated patterns of cell development in OSCC that are predictably associated with drug response. Our work provides pan-cancer insights into TC and LE biology and interactive spatial atlases ( http://www.pboselab.ca/spatial_OSCC/ ; http://www.pboselab.ca/dynamo_OSCC/ ) that can be foundational for developing novel targeted therapies.

NCBP2 and TFRC are novel prognostic biomarkers in oral squamous cell carcinoma.

There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV-negative OSCC patients. Expression of NCBP2 and TFRC is significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease-specific survival, and progression-free interval in an in-house cohort of HPV-negative OSCC patients. Finally, due to a lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behaviour. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. Differential expression analysis revealed the upregulation of several tumour-promoting genes in patients with high NCBP2 expression. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV-negative OSCC.

The Population-based Impact of Adjuvant Chemotherapy on Outcomes in T2N0M0 Non-Small Cell Lung Cancer.

OBJECTIVES: The value of adjuvant chemotherapy in T2N0M0 non-small-cell lung cancer (NSCLC) is unclear. Some current guidelines suggest adjuvant chemotherapy be considered for patients with tumors ≥4 cm. Prior population-based evaluations lacked lung cancer-specific survival (LCSS) and health insurance status. The authors aimed to identify predictors of adjuvant chemotherapy use and assess its real-world benefit in T2N0M0 NSCLC. MATERIALS AND METHODS: The authors included patients who underwent surgery for T2N0M0 NSCLC in a large Canadian province with universal health care between 2004 and 2015, grouping cases by adjuvant chemotherapy receipt. They identified predictors of chemotherapy use with logistic regression and correlates of overall survival (OS) and LCSS using Cox regression. RESULTS: The authors analyzed 967 patients. The median age was 68 years (interquartile range, 61 to 74), 455 (47%) were men, and 164 (17%) received adjuvant chemotherapy. Sex, tumor location, and laterality were similar between groups. Younger age, lower Charlson comorbidity score, large cell histology, and tumor size ≥4 cm were associated with a higher likelihood of chemotherapy receipt (all P<0.05). In the entire cohort and in the ≥4 and ≥5 cm subgroups, chemotherapy improved OS but not LCSS on univariate analysis. Chemotherapy was not associated with OS or LCSS in multivariate analysis (OS hazard ratio [HR], 0.925; 95% confidence interval [0.693-1.236], P=0.598, 0.725 [0.454-1.157], P=0.177 in the ≥4 cm group; LCSS HR, 1.196 [0.843-1.695], P=0.316, 0.917 [0.533-1.577], P=0.754 in the ≥4 cm group). CONCLUSION: Adjuvant chemotherapy was not associated with improved survival in this population-based T2N0M0 NSCLC cohort, even for ≥4 or ≥5 cm tumors, suggesting that it has a limited role in real-world practice.

Papular granuloma annulare of palms and soles: case report of a rare presentation.

We report the case of a 44-year-old Indian male patient who presented with mildly tender isolated papular lesions confined to the palms of the hands and soles of the feet. The histopathology was characteristic of granuloma annulare. There was an excellent response with 4-week treatment with a potent topical steroid ointment and no recurrence was reported at the follow-up one year later. This report is interesting because of the rare presentation of a common disease.

Anal cytology and p16 immunostaining for screening anal intraepithelial neoplasia in HIV-positive and HIV-negative men who have sex with men: a cross-sectional study.

Summary Akin to cervical cancer in sexually-active women, men who have sex with men (MSM) are predisposed to anal cancers, especially those with HIV co-infection. This cross-sectional study endeavored to assess the prevalence of anal dysplasia using Pap smears and p16 immunostaining amongst Indian MSM. A total of 31 consecutive HIV-positive and 34 HIV-negative MSM, from a cohort of sexually transmitted infection clinic attendees, underwent anal cytological evaluation with Pap smear and p16 staining. Chi square test and coefficient of correlation were used for comparison. Eighteen (27.7%) had abnormal anal cytology; increased in HIV-positive as compared to HIV-negative men (35% versus 20%, p = 0.180). Similarly, both low-grade (25.8% versus 17.6%) and high-grade lesions (8.3% versus 4.8%) were comparable in HIV-positive and HIV-negative group. Thirteen (20%) smears were p16-positive with a sensitivity and specificity for anal dysplasia of 72.3% and 100%, respectively. Anal cytology may be used to screen for anal dysplasia in MSM irrespective of HIV status. Furthermore, the addition of p16, with greater specificity for high-grade lesions, may improve diagnostic accuracy especially for high-grade lesions. A larger study to further corroborate these observations is warranted.

Subaortic membrane with rupture of sinus of Valsalva presented with infective endocarditis and its thromboembolic complications.

Rupture of the sinus of Valsalva (RSOV) is an uncommonly encountered condition. It can present with wider manifestations ranging from an asymptomatic murmur to cardiogenic shock. The case discussed in this report also had subaortic membrane which usually presents with subvalvular aortic stenosis, left ventricular hypertrophy, myocardial ischemia and sudden death. Corrective cardiac surgery was advised, but due to financial constraints, the patient could not be operated and he died. Here, the authors report for the first time an unusual presence of both RSOV and subaortic membrane and the patient presented with thromboembolic complication resulting from infective endocarditis.