Thread by @AnnaVaharautio

How do metastatic #ovariancancer tumors change during #chemotherapy to survive, eventually killing the patient? See our longitudinal #scRNAseq analysis, now out @ScienceAdvances, with accessible data & tools.
science.org/doi/10.1126/sc…
A 🧵 below (1/9)

We collected a unique set of paired, metastatic tumor specimens from 11 high-grade serous patients treated in @TyksVsshp (by @mijohy & colleagues) before and after neo-adjuvant chemotherapy, and analysed dissociated tumors with scRNA-seq. (2/9)

Unlike stroma or immune cells, cancer cells had distinctly patient-specific profiles. To find the hidden, shared states from these genetically heterogeneous tumor specimens, @KaiyangZhang @HautaniemiLab developed a new clustering method, PRIMUS (3/9)

PRIMUS simultaneously clusters and denoises data, and benchmarks well against batch removal tools, especially on unbalanced data. I know you want to test it on your data, so go ahead!! Available with tutorials: github.com/KaiyangZ/PRIMUS (4/9)

Combination of paired, clinical tumor specimens and new analysis approach revealed that a stress-related cancer cell state consistently increases during chemotherapy and is associated with inflammatory signaling with the surrounding stroma. (5/9)

We further show that the stress-associated state is subclonally enriched during chemotherapy as low-stress subclones fail to re-initiate proliferation after NACT. Increased levels of stress in treatment-naive tumors are associated with short chemoresponse.(6/9)

Our discovery can help to identify tumors that will likely have poor response to upcoming chemotherapy. Preventing chemo-induced inflammatory signaling between cancer cells and stroma could offer venues for effective combinatorial treatments. (7/9)

Excellent collaboration between @helsinkiuni, @TyksVsshp and @UniTurku! Thank you @KaiyangZhang, @e_p_erkan, @SanazJamalzadeh, @JunDai45733898, @KaipioKatja, Tarja Lamminen, Naziha Mansuri, @KaisaHuhtinen, @jaanaoikkonen, @OlliCarpen, @hshiet ,..(8/9)

… @mijohy,@annimariav, Antti Häkkinen and @Sampsa_H for contributing and @HerculesOvCa, @SuomenAkatemia, @Syopasaatio, @SigridJuselius, @erapermedparis & @deciderproject for funding the project!! (9/9)

And if you have HGSS organoid & CAF co-cultures, we’d love to collaborate to test preventing chemo-induced inflammatory signaling between cancer cells and stroma!