Fig. 8: IQSEC1 is associated with metastasis, treatment resistance, and poor clinical outcome. | Nature Communications

Fig. 8: IQSEC1 is associated with metastasis, treatment resistance, and poor clinical outcome.

From: An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism

Fig. 8

a and b CN increase in IQSEC1, ARF5, ARF6 across indicated cohorts. AD, prostate adenocarcinoma; NE neuroendocrine; CR Castrate-resistant. c–j Clinical metrics (% samples) between IQSEC1 CN-amplified (+) or non-amplified group (−) for c 3p Status (−, n = 420; +, n = 32), d Gleason Score (−, n = 779; +, n = 53), e Tumour Lymph Node Status. N0, no positivity. N1, positivity. (−, n = 381; +, n = 36), f Sample Type (−, n = 1,797; +, n = 272), g Tumour Anatomic Site (−, n = 525; +, n = 78), h androgen deprivation therapy. Luteinizing hormone-releasing hormone, LHRH (−, n = 484; +, n = 30), i person neoplasm status (−, n = 299; +, n = 77), and j androgen receptor (AR) isoform v7 mRNA levels (Log2) (−, n = 221; +, n = 69). p values, c–i Chi-squared Test or j Kruskal–Wallis Test; Q values, Benjamini–Hochberg adjustment. Box-and-whiskers plots: 10–90 percentile; +, mean; dots, outliers; midline, median; boundaries, quartiles. k Prostate-specific antigen (PSA) serum levels (Log2) in IQSEC1, ARF5, ARF6 CN increase (+, n = 22) or not (−, n = 86) patients. Q value, Kruskal–Wallis Test. Box-and-whiskers plots: 10–90 percentile; +, mean; dots, outliers; midline, median; boundaries, quartiles. l–n Copy Number Alteration (l, m) or (n) mutation frequencies between IQSEC1 CN-amplified (n = 849) or unaltered (n = 2308) patients. Group association: Red, IQSEC1 CN increase; blue, unaltered. Q-values, one-sided Fisher exact test with Benjamini–Hochberg adjustment. o and p Overall survival (% patients, months), unaltered compared to (i) IQSEC1 CN increase or (ii) combined IQSEC1, ARF5, ARF6 CN increase for o cohorts in A (n = 665) or p pan-cancer TCGA cohorts (n = 9307). p-values, Log-rank t-test. q and r Matched Normal (blue) and prostate tumour (Tumour, red) Log2-normalised IQSEC1 mRNA for q total isoforms or r v2-v1 ratio. values. Line: unbroken, tumour-increased; dotted, tumour-decreased. n = 52. p-values, Independent Groups t-test. s IQSEC1 mRNA log2-normalised normal–tumour ratio across pan-cancer TCGA cohorts for total (green-magenta), individual isoforms (blue-red), or v2-v1 ratio (grey-orange). Circle size, p-value, Independent Groups t-test. Normal tissue (n = 643), tumour tissue (n = 6716). Supplementary Table 2 contains tumour-type data. t PI3K-AKT pathway (RPPA of pan-cancer TCGA cohorts) from median-split of Log2-transformed IQSEC1 mRNA. Red, high IQSEC1 co-occurring; blue, low IQSEC1 co-occurring. Only cancer types presenting increased AKT_pS473 included. Row sorting from dendrogram. Circle size, p-value, Independent Groups t-test.

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