The Kaiser Permanente Research Bank Cancer Cohort: a collaborative resource to improve cancer care and survivorship.

BACKGROUND: The Kaiser Permanente Research Bank (KPRB) is collecting biospecimens and surveys linked to electronic health records (EHR) from approximately 400,000 adult KP members. Within the KPRB, we developed a Cancer Cohort to address issues related to cancer survival, and to understand how genetic, lifestyle and environmental factors impact cancer treatment, treatment sequelae, and prognosis. We describe the Cancer Cohort design and implementation, describe cohort characteristics after 5 years of enrollment, and discuss future directions. METHODS: Cancer cases are identified using rapid case ascertainment algorithms, linkage to regional or central tumor registries, and direct outreach to KP members with a history of cancer. Enrollment is primarily through email invitation. Participants complete a consent form, survey, and donate a blood or saliva sample. All cancer types are included. RESULTS: As of December 31, 2020, the cohort included 65,225 cases (56% female, 44% male) verified in tumor registries. The largest group was diagnosed between 60 and 69 years of age (31%) and are non-Hispanic White (83%); however, 10,076 (16%) were diagnosed at ages 18-49 years, 4208 (7%) are Hispanic, 3393 (5%) are Asian, and 2389 (4%) are Black. The median survival time is 14 years. Biospecimens are available on 98% of the cohort. CONCLUSIONS: The KPRB Cancer Cohort is designed to improve our understanding of treatment efficacy and factors that contribute to long-term cancer survival. The cohort's diversity - with respect to age, race/ethnicity and geographic location - will facilitate research on factors that contribute to cancer survival disparities.

Semi-quantitative, high throughput analysis of SARS-CoV-2 neutralizing antibodies: Measuring the level and duration of immune response antibodies post infection/vaccination.

The question associated with efficacy and longevity of SARS-CoV-2 protection post-vaccination is paramount. The cPass surrogate virus neutralization test (sVNT) has gained popularity globally as a dual application assay for: 1. Accurate SARS-CoV-2 population surveillance (seroprevalence) analysis and 2. Revealing the presence of antibodies that block and effectively neutralize the interaction between the SARS-CoV-2 receptor binding domain and the host cell ACE2 receptor in recovered or vaccinated individuals. This study describes an approach for accurate quantification of neutralizing antibodies using the cPass sVNT with an automated workflow on the Tecan EVO and Dynex Agility platforms that is applicable to other liquid handling systems. This methodology was used to assess the stability of SARS-CoV-2 neutralizing antibodies between freeze/thaw and refrigerated sample storage conditions. Furthermore, a subset of twenty-five samples from SARS-CoV-2 infected/recovered individuals revealed a 600-fold difference in the neutralizing antibody response where low titers were represented in about half of the samples. Finally, pre- and post-vaccination samples were tested for neutralizing antibodies using the qualitative and semi-quantitative cPass sVNT protocols revealing undetectable or relatively low levels after the first vaccine dose and a decline in levels longitudinally over the months following the second dose. This wide range in neutralizing (blocking) antibodies from both natural infection and vaccination supports a differential immune response that may be attributed to several physiological and genetic factors underlining the potential for measuring SARS-CoV-2 neutralizing antibody titer levels post-vaccination to help ensure robust and prolonged immunity.

Molecular signature and pathway analysis of human primary squamous and adenocarcinoma lung cancers.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a poor response to chemotherapy and low survival rate. This unfavorable treatment response is likely to derive from both late diagnosis and from complex, incompletely understood biology, and heterogeneity among NSCLC subtypes. To define the relative contributions of major cellular pathways to the biogenesis of NSCLC and highlight major differences between NSCLC subtypes, we studied the molecular signatures of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), based on analysis of gene expression and comparison of tumor samples with normal lung tissue. Our results suggest the existence of specific molecular networks and subtype-specific differences between lung ADC and SCC subtypes, mostly found in cell cycle, DNA repair, and metabolic pathways. However, we also observed similarities across major gene interaction networks and pathways in ADC and SCC. These data provide a new insight into the biology of ADC and SCC and can be used to explore novel therapeutic interventions in lung cancer chemoprevention and treatment.

Exploring molecular pathways of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a high rate of proliferation and metastasis, as well as poor prognosis for advanced-stage disease. Although TNBC was previously classified together with basal-like and BRCA1/2-related breast cancers, genomic profiling now shows that there is incomplete overlap, with important distinctions associated with each subtype. The biology of TNBC is still poorly understood; therefore, to define the relative contributions of major cellular pathways in TNBC, we have studied its molecular signature based on analysis of gene expression. Comparisons were then made with normal breast tissue. Our results suggest the existence of molecular networks in TNBC, characterized by explicit alterations in the cell cycle, DNA repair, nucleotide synthesis, metabolic pathways, NF-κB signaling, inflammatory response, and angiogenesis. Moreover, we also characterized TNBC as a cancer of mixed phenotypes, suggesting that TNBC extends beyond the basal-like molecular signature and may constitute an independent subtype of breast cancer. The data provide a new insight into the biology of TNBC.