The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy

Abstract

The calpains are a family of intracellular cysteine proteases that function in a variety of important cellular functions, including cell signalling, motility, apoptosis and survival. In early invasive breast cancer expression of calpain-1, calpain-2 and their inhibitor, calpastatin, have been associated with clinical outcome and clinicopathological factors.The expression of calpain-1, calpain-2 and calpastatin was determined using immunohistochemistry on core biopsy samples, in a cohort of large but operable inflammatory and non-inflammatory primary breast cancer patients treated with neoadjuvant chemotherapy. Information on treatment and prognostic variables together with long-term clinical follow-up was available for these patients. Diagnostic pre-chemotherapy core biopsy samples and surgically excised specimens were available for analysis.Expression of calpastatin, calpain-1 or calpain-2 in the core biopsies was not associated with breast cancer specific survival in the total patient cohort; however, in patients with non-inflammatory breast cancer, high calpastatin expression was significantly associated with adverse breast cancer-specific survival (P=0.035), as was low calpain-2 expression (P=0.031). Low calpastatin expression was significantly associated with adverse breast cancer-specific survival of the inflammatory breast cancer patients (P=0.020), as was low calpain-1 expression (P=0.003).In conclusion, high calpain-2 and low calpastatin expression is associated with improved breast cancer-specific survival in non-inflammatory large but operable primary breast cancer treated with neoadjuvant chemotherapy. In inflammatory cases, high calpain-1 and high calpastatin expression is associated with improved breast cancer-specific survival. Determining the expression of these proteins may be of clinical relevance. Further validation, in multi-centre cohorts of breast cancer patients treated with neoadjuvant chemotherapy, is warranted.

Calpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme

“…With the development of precision medicine, it is likely that information gathered on patient biopsy or resection samples will need to be utilized for guiding decisions on how responsive colon cancer cases will be to calpain‐2 inhibitors. This is highlighted by studies showing that expression of calpain‐1 and ‐2 along with calpastatin can vary within cohorts of cancer patients and these data may be used to predict disease progression or survival . While calpain‐1 and calpastatin levels varied widely in the cancer cell lines we examined in this study, calpain‐2 levels were consistently detected and showed interesting patterns of low, moderate, and high expression.…”

A framework for transcriptome-wide association studies in breast cancer in diverse study populations

“…Mutations in AURKA and PIK3CA have previously been shown to be significantly associated with breast cancer survival rates [31][32][33]. Less is known about the involvement of SER-PINB5 and CAPN13 in breast cancer survival, though they have been identified in studies into breast cancer progression [48][49][50][51][52]. These four loci merit further studies for validation and functional characterization, both in large GWAS cohorts and using in vitro studies.…”

Overexpression of CAPN2 promotes cell metastasis and proliferation via AKT/mTOR signaling in renal cell carcinoma

“…Therefore, it is of great urgency to identify novel representative biomarkers for RCC tumor promotion and therapeutic treatment. Accumulating evidence has indicated that CAPN2, a calcium-activated protease, could participate in tumor progression and carcinogenesis in multiple cancer types including prostate cancer, ovarian cancer, breast cancer and hepatocellular carcinoma [ 16 , 17 , 20 – 22 ]. However, the function of CAPN2 in RCC and its underlying mechanisms remain unclear.…”